-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neocortical differentiation and hippocampal integration of non-meaningful items and their spatial location
Resolving interference between similar inputs is a critical feature of adaptive memory systems. Computational theories of the medial temporal lobe posit that the dentate gyrus and CA3 (CA3DG) subfields of the hippocampus are ideally suited to reduce interference via a process called pattern separation. Whereas neocortical areas upstream of the hippocampus have been shown to play a role in content-specific (e.g., spatial or object-related) interference reduction, the CA3DG is traditionally viewed as a domain-general pattern separator. Recent work also drew attention to the role of frontal and parietal control areas in allocating resources according to task demands during mnemonic discrimination, exerting top-down control over the medial temporal lobe. However, extant evidence in humans is almost solely based on mnemonic discrimination tasks involving everyday items, potentially confounding retrieval processes with pattern separation. Here, we studied pattern separation in a 'process-pure' manner, utilizing non-meaningful fractal images. We acquired full-brain high-resolution functional MRI data of 39 participants (mean age (SD) = 22.6 (2.4) years, 19 females) while they studied fractals with varying degrees of interference in either their spatial or object features. Building upon the idea that the repetition of a stimulus results in a diminished BOLD response in areas involved in the processing of that stimulus (repetition suppression), we expected that regions engaged in pattern separation of objects or locations would decrease their response to repetitions, but not to highly similar (interference-inducing) items. We found that the parahippocampal cortex contributes to interference reduction in the spatial domain, while the perirhinal cortex contributes to interference reduction in the object domain. The frontoparietal control network was recruited during the encoding of both object and location lures, and displayed strengthened within- and cross-network connectivity in response to lures. Contrary to our expectations, the CA3DG showed repetition suppression to both exact repetitions and highly similar lures, indicating a lack of sensitivity to small differences in interfering stimuli. Altogether, these results are in line with content-specific neocortical interference reduction in the medial temporal lobe, possibly orchestrated by the frontoparietal control network, but challenge the view of CA3DG as a universal pattern separator.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
RIPK2 is crucial for the microglial inflammatory response to bacterial muramyl dipeptide but not to lipopolysaccharide
Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is a kinase that plays an essential role in the modulation of innate and adaptive immune responses. As a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs), it is implicated in the signaling triggered by recognition of microbe-associated molecular patterns by NOD1/2 and TLRs. Upon activation of these innate immune receptors, RIPK2 mediates the release of pro-inflammatory factors by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-{kappa}B). However, whether RIPK2 is essential for downstream inflammatory signaling following the activation of NOD1/2, TLRs, or both remains controversial. In this study, we examined the role of RIPK2 in NOD2- and TLR4-dependent signaling cascades following stimulation of microglial cells with bacterial muramyl dipeptide (MDP), a NOD2 agonist, or lipopolysaccharide (LPS), a TLR4 agonist. We utilized a highly specific proteolysis targeting chimera (PROTAC) molecule, GSK3728857A, and found dramatic degradation of RIPK2 in a concentration- and time-dependent manner. Importantly, the PROTAC completely abolished MDP-induced increases in iNOS and COX-2 protein levels and pro-inflammatory gene transcription of Nos2, Ptgs2, Il-1{beta}, Tnf, Il6, Ccl2, and Mmp9. However, increases in iNOS and COX-2 proteins and pro-inflammatory gene transcription induced by the TLR4 agonist, LPS, were only slightly attenuated with the GSK3728857A pretreatment. Further findings revealed that the RIPK2 PROTAC completely blocked the phosphorylation and activation of p65 NF-{kappa}B and p38 MAPK induced by MDP, but it had no effects on the phosphorylation of these two mediators triggered by LPS. Collectively, our findings strongly suggest that RIPK2 plays an essential role in the inflammatory responses of microglia to bacterial MDP but not to LPS.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats
The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) agents are promising antagonists that selectively inhibit soluble TNF signaling, while preserving the beneficial effects of transmembrane TNF. Previous studies have tested the protective potential of DN-TNF-based therapy in toxin-based PD models. Here we test for the first time the protective potential of a DN-TNF therapeutic against alpha-synuclein-driven neurodegeneration in the viral vector-based PD rat model. To do so, we administered the DN-TNF agent XPro1595 subcutaneously for a period of 12 weeks. In contrast to previous studies using different PD models, neuroprotection was not achieved by systemic XPro1595 treatment. Alpha-synuclein-induced loss of nigrostriatal neurons, accumulation of pathological inclusions and microgliosis was detected in both XPro1595- and saline-treated animals. XPro1595 treatment increased the percentage of the hypertrophic/ameboid Iba1+ cells in SN and reduced the striatal MHCII+ microglia in the striatum of alpha-synuclein-overexpressing animals. However, the treatment did not prevent the MHCII upregulation seen in the SN of the model, nor the increase of CD68+ phagocytic cells. Therefore, despite an apparently positive immune effect, this did not suffice to protect against viral vector-derived alpha-synuclein-induced neurotoxicity. Further studies are warranted to better elucidate the therapeutic potential of soluble TNF inhibitors in PD.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The role of repetition in context-dependent preference
The context in which decisions are learned can influence what choices we prefer in new situations. Such dependencies are well replicated and often lead to decision biases, i.e. choices that deviate from rational choice theory. We propose a simple computational model of such biases. To test the model, we analyzed behavioral data from 351 male and female participants in a series of nine value-based decision tasks and re-analyze six previously published datasets (n = 350 participants). Our results show that the combination of two basic principles, learning by reward, and repetition of decisions, is sufficient to explain biased preferences across all 15 datasets. Using standard analysis and hierarchical Bayesian model comparison we found that the proposed model provides a better explanation than previous accounts. In addition, our results show that higher choice frequency is linked to higher subjective valuation and lower value uncertainty. Results indicate that repetition is an important mechanism in shaping preferences.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Human BNST volume is not simply sexually dimorphic
"The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region", is a claim prevalent across rodent and human neuroscience research, with particular emphasis on its substantially larger size in males. Despite the pervasiveness of this claim, with potential implications for understanding sex differences in anxiety and substance use disorders, inspection of prior literature reveals a complex and nuanced picture. Direct evidence for larger male BNST size in humans comes solely from a handful of mostly small-scale post-mortem studies, which show either no, moderate, or very large differences, therefore indicating the need for a larger systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol of the BNST, which was applied to T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing post-mortem data, and controlling for total brain volume, age, and sibship, we find little evidence for total BNST volume differences between males and females. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Distinct cortical spatial representations learned along disparate visual pathways
Recent experimental studies have discovered diverse spatial properties, such as head direction tuning and egocentric tuning, of neurons in the postrhinal cortex (POR) and revealed how the POR spatial representation is distinct from the retrosplenial cortex (RSC). However, how these spatial properties of POR neurons emerge is unknown, and the cause of distinct cortical spatial representations is also unclear. Here, we build a learning model of POR based on the pathway from the superior colliculus (SC) that has been shown to have motion processing within the visual input. Our designed SC-POR model demonstrates that diverse spatial properties of POR neurons can emerge from a learning process based on visual input that incorporates motion processing. Moreover, combining SC-POR model with our previously proposed V1-RSC model, we show that distinct cortical spatial representations in POR and RSC can be learnt along disparate visual pathways (originating in SC and V1), suggesting that the varying features encoded in different visual pathways contribute to the distinct spatial properties in downstream cortical areas.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cerebellar climbing fibers signal flexible, rapidly adapting reward predictions
Classical models of cerebellar computation posit that climbing fibers (CFs) operate according to supervised learning rules, correcting movements by signaling the occurrence of motor errors. However, recent findings suggest that in some behaviors, CF activity can exhibit features that resemble the instructional signals necessary for reinforcement learning, namely reward prediction errors (rPEs). Despite these initial observations, many key properties of reward-related CF responses remain unclear, thus limiting our understanding of how they operate to guide cerebellar learning. Here, we have measured the postsynaptic responses of CFs onto cerebellar Purkinje cells using two-photon calcium imaging to test how they respond to learned stimuli that either do or do not predict reward. We find that CFs can develop generalized responses to similar cues of the same modality, regardless of whether they are reward predictive. However, this generalization depends on temporal context, and does not extend across sensory modalities. Further, learned CF responses are flexible, and can be rapidly updated according to new reward contingencies. Together these results suggest that CFs can generate learned, reward-predictive responses that flexibly adapt to the current environment in a context-sensitive manner.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Reprogrammed Human Lateral Ganglionic Eminence Precursors Generate Striatal Neurons and Restore Motor Function in a Rat Model of Huntington's Disease.
Background: Huntington's disease (HD) is a genetic neurological disorder predominantly characterised by the progressive loss of GABAergic medium spiny neurons in the striatum resulting in motor dysfunction. One potential strategy for the treatment of HD is the development of cell replacement therapies to restore neuronal circuitry and function by the replacement of lost neurons. We propose the generation of lineage-specific human lateral ganglionic eminence precursors (hiLGEP) using direct reprogramming technology provides a novel and clinically viable cell source for cell replacement therapy for HD. Methods: hiLGEPs were derived by direct reprogramming of adult human dermal fibroblasts (aHDFs) using chemically modified mRNA (cmRNA) and a defined reprogramming medium. hiLGEPs were differentiated in vitro using an optimised striatal differentiation medium. Acquisition of a striatal precursor and neural cell fate was assessed through gene expression and immunocytochemical analysis of key markers. hiLGEP-derived striatal neuron functionality in vitro was demonstrated by calcium imaging using Cal-520. To investigate the ability for hiLGEP to survive, differentiate and functionally integrate in vivo, we transplanted hiLGEPs into the striatum of quinolinic acid (QA)-lesioned rats and performed behavioural assessment using the cylinder test over the course of 14 weeks. Survival and differentiation of hiLGEPs was assessed at 8 and 14-weeks post-transplant by immunohistochemical analysis. Results: We demonstrate the capability to generate hiLGEPs from aHDFs using cmRNA encoding the pro-neural genes SOX2 and PAX6, combined with a reprogramming medium containing Go6983, Y-27632, N-2 and Activin A. hiLGEPs generated functional DARPP32+ neurons following 14 days of culture in BrainPhys(TM) media supplemented with dorsomorphin and Activin A. We investigated the ability for hiLGEPs to survive transplantation, differentiate to medium spiny-like striatal neurons and improve motor function in the QA lesion rat model of HD. Fourteen weeks after transplantation, we observed STEM121+ neurons co-expressing MAP2, DARPP32, GAD65/67, or GABA. Rats transplanted with hiLGEPs also demonstrated reduction in motor function impairment as determined by spontaneous exploratory forelimb use when compared to saline transplanted animals. Conclusion: This study provides proof-of-concept and demonstrates for the first time that aHDFs can be directly reprogrammed to hiLGEPs which survive transplantation, undergo neuronal differentiation to generate medium spiny-like striatal neurons, and reduce functional impairment in the QA lesion rat model of HD.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder
Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics and the contribution of individual cell types remain largely unknown. We present an in-depth analysis of molecular changes in the ventral striatum in CUD at multi-omics and single-cell resolution. Integrative multi-omics analyses of microRNA-seq, RNA-seq, and proteomics datasets in 41 individuals and single-nuclei RNA-seq in a subset of 16 individuals revealed conserved deregulation of metabolic pathways, oxidative phosphorylation, and glutamatergic signaling. Cell type-specific analyses identified inverse metabolic pathway deregulation patterns in glial and neuronal cells, notably in astrocytes and medium spiny neurons (MSNs). Characterizing astrocyte-neuron crosstalk revealed altered glutamatergic and cell adhesion signaling in CUD. By applying a comprehensive multi-omics analytical framework, our study provides novel insights into CUD-associated molecular changes in the ventral striatum, suggesting astrocytes, MSNs, and their crosstalk as particularly perturbed in CUD.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Melanocortin 4 Receptor-Dependent Mechanism of ACTH in Preventing Anxiety-Like Behaviors and Normalizing Astrocyte Proteins After Early Life Seizures
Epilepsy, affecting millions globally, often leads to significant cognitive and psychiatric comorbidities, particularly in children. Anxiety and depression are particularly prevalent, with roughly a quarter of pediatric epilepsy patients having a comorbid diagnosis. Current treatments inadequately address these issues. Adrenocorticotropic hormone (ACTH), a melanocortin peptide, has shown promise in mitigating cognitive deficits after early life seizures (ELS), potentially through mechanisms beyond its canonical action on melanocortin 2 receptor (MC2R). This study explores the hypothesis that recurrent ELS is associated with long-term anxiety, and that treatment with ACTH can prevent this anxiety through a mechanism that involves melanocortin 4 receptors (MC4R) in the brain. Our findings reveal that ACTH ameliorates anxiety-like behavior associated with ELS, without altering seizure parameters, in wildtype (WT) mice but not in MC4R knockout (KO) mice. Our findings also show that knocking-in MC4R in either neurons or astrocytes was able to rescue the anxiety-like behavior after ACTH treatment. Further, our results show that ACTH normalizes important astrocytic proteins like Glial Fibrillary Acidic Protein (GFAP) and Aquaporin-4 (AQP4) after ELS. This suggests that ACTH beneficial effects on anxiety are mediated through MC4R activation in both neuronal and astrocytic populations. This study underscores the therapeutic potential of targeting MC4R in epilepsy treatment, highlighting its role in mitigating cognitive impairments and anxiety-like behaviors associated with ELS.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Characteristics of spatial summation in the magnocellular, parvocellular, and koniocellular pathways
In this study, we characterize the spatial summation properties of targeted magnocellular, parvocellular, and koniocellular pathways within the central 20 degrees of visual field using chromatic transformations in DKL color space. For the magnocellular and koniocellular conditions, critical areas of complete spatial summation were found for all eccentricities. For the parvocellular conditions, complete spatial summation was absent within the stimulus size ranges tested. We also describe an anatomically and physiologically motivated model of receptive field pooling using probability summation. Model simulations suggest that the critical area of summation can be explained by the dendritic field size of underlying retinal ganglion cells, corroborating our psychophysical data.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Mitochondrial Dysfunction in Alzheimer's Disease Is Driven By Excess ER-Calcium Release in Patient-Derived Neurons
Tight regulation of mitochondrial Ca2+ is essential for neuronal bioenergetics and cellular metabolism. Ca2+ transfer from ER-localized ryanodine receptors (RyR) and inositol triphosphate receptors (IP3R) to the mitochondria maintains a steady Ca2+ source that fuels oxidative phosphorylation and ATP production. In Alzheimer's disease (AD), RyR-evoked Ca2+ release is markedly increased, contributing to synaptic deficits, protein mishandling, and memory impairment. Here, we demonstrate that dysregulated RyR-Ca2+ release directly compromises mitochondrial activity and is an early contributor to AD cellular pathology. We measured an array of mitochondrial functions using fluorescent biosensors and optical imaging in RyR2-expressing HEK cells and iPSC-derived neurons from familial AD and nonAD patients. In neurons from AD patients, resting mitochondrial Ca2+ levels were elevated alongside increased free radical production and higher caspase-3 activity relative to nonAD neurons. RyR-evoked Ca2+ release further potentiated pathogenic mitochondrial responses in AD neurons, with increased Ca2+ uptake and exaggerated membrane depolarization. Additionally, clearance of damaged mitochondria was impaired in AD neurons, demonstrating consequences from dysfunctional lysosomes. Notably, impairments to mitochondria in AD neurons were largely prevented with the RyR negative allosteric modulator, Ryanodex. These findings highlight how excess RyR-Ca2+ release broadly contributes to early cellular pathology in AD which includes a cascade of ER, lysosomal, and mitochondrial deficits culminating in neuronal decline and degeneration. Additionally, pharmacological suppression of RyR-Ca2+ release preserves mitochondrial, ER and lysosomal function, thus providing a novel and effective therapeutic.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions
Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Astrocytic HIV-1 Nef expression decreases glutamate transporter expression in the nucleus accumbens and increases cocaine-seeking behavior in rats
Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease, contributing to neurotoxicity and neuroin-flammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with cART, HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin. This study investigates the relationship that exists between Nef, glutamate homeostasis, and cocaine in the NAc, a critical brain region associated with drug motiva-tion and reward. Using a rat model, we compared the effects of astrocytic Nef and cocaine by molecular analysis of glutamate transporters in the NAc. We further conducted be-havioral assessments for cocaine self-administration to evaluate cocaine-seeking behavior. Our findings indicate that both cocaine and Nef independently decrease the expression of the glutamate transporter GLT-1 in the NAc. Additionally, rats with astrocytic Nef ex-pression exhibited increased cocaine-seeking behavior but demonstrated sex dependent molecular differences after behavioral paradigm. In conclusion, our results suggest the expression of Nef intensifies cocaine-induced alterations in glutamate homeostasis in the NAc, potentially underlying increased cocaine-seeking. Understanding these interactions better may inform therapeutic strategies for managing cocaine use disorder in HIV-infected individuals.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Integration of spatial transcriptomics with immunofluorescence staining reveals spatial heterogeneity and plasticity of astrocytes in experimental glioblastomas
Astrocytes comprise ~50% of all brain cells and present distinct morphological, molecular and functional properties in different brain regions. In glioblastoma (GBM), an aggressive primary brain tumour, tumour-associated astrocytes (TAAs) become activated and exhibit different transcriptomic profiles, morphology and functions supporting disease progression. Heterogeneity and specific roles of TAAs within various regions of tumours are poorly known. Advancements of single-cell and spatial transcriptomics allow to profile tumours at unprecedented resolution revealing cell phenotypes, hidden functionalities and spatial architecture in disease-specific context. We combined spatial transcriptomics and multiple immunofluorescent staining to visualize TAAs heterogeneity and location of various subpopulations in intracranial murine gliomas. Using distinct gene expression profiles, we identified subtypes of TAAs with distinct localization and inferred their specialized functionalities. Gene signatures associated with TAAs reflected their reprograming in the tumour microenvironment (TME), revealed their multiple roles and potential contributing factors shaping the local milieu. Using spatial correlation analysis of the spots, we inferred the interactome of Slc1a2 (encoding a glutamate transporter) with the other markers of TAAs based on segregated areas of the tumour. The designer RGD peptide blocking tumour-microglia communications, alters the spatial distribution of TAAs in experimental gliomas providing insights into potential mechanisms. Spatial transcriptomics combined with multiple staining unveils multiple functional phenotypes of TAAs and interactions within TME. It shows their distinct morphology and unveils different roles in various regions of the tumour. We demonstrate the glioma-induced heterogeneity of TAAs and their adaption to the pharmacologically-induced modification of the immunosuppressive TME.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Deep generative networks reveal the tuning of neurons in IT and predict their influence on visual perception
Finding the tuning of visual neurons has kept neuroscientists busy for decades. One approach to this problem has been to test specific hypotheses on the relevance of a visual property (e.g. orientation or color), build a set of 'artificial' stimuli that vary along that property and then record neural responses to those stimuli. Here, we present a complementary, data-driven method to retrieve the tuning properties of visual neurons. Exploiting deep generative networks and electrophysiology in monkeys, we first used a method to reconstruct any stimulus from its evoked neuronal activity in the inferotemporal cortex (IT). Then, by arbitrarily perturbing the response of individual cortical sites in the model, we generated naturalistic and interpretable sequences of images that strongly influence neural activity of that site. This method enables the discovery of previously unknown tuning properties of high-level visual neurons that are easily interpretable, which we tested with carefully controlled stimuli. When we knew which images drove the neurons, we activated the cells with electrical microstimulation and observed a predicable shift of the monkey perception in the direction of the preferred image. By allowing the brain to tell us what it cares about, we are no longer limited by our experimental imagination.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Predicting and phase targeting brain oscillations in real-time
Objective: Closed-loop neurostimulation (CLNS) procedures, aligning stimuli with electrical brain activity, are quickly gaining popularity in neuroscience. They have been employed to reveal causal links between neural activity patterns and function, and to explore therapeutic effects of electroencephalography (EEG-)guided stimulations during sleep. Most CLNS procedures are developed for a single purpose, detecting one specific pattern of interest in the EEG. Furthermore, most procedures have limited, if any, flexibility to adapt to temporal or interindividual variance in the signal, which means they wouldn't work optimally across the full physiological phenomenology. Approach: Here we present a new approach to CLNS, based on real-time signal modelling to predict brain activity, allowing targeting of a broad variety of oscillatory dynamics. Intrinsic to the modelling approach is adaptation to signal variance, such that no personalization steps prior to use are necessary. We systematically assess stimulus targeting performance of modelling-based CLNS (M-CLNS), across a wide range of brain oscillation frequencies and phases in human and rodent neurophysiological signals. Main results: Our results show high performance for all target phases and frequency bands, including slow oscillations, theta and alpha waves. Significance: These findings highlight the general applicability and adaptability of M-CLNS, which also favors its application in populations with an atypical oscillatory signature, like clinical or elderly populations. In conclusion, M-CLNS provides a promising new tool for neural activity-dependent stimulation in both experimental research and therapeutic applications, such as enhancing deep sleep in patients with sleep disorders.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Recovery from Spreading Depolarization is slowed by aging and accelerated by antioxidant treatment in locusts
Spreading depolarization (SD) temporarily shuts down neural processing in nervous systems with effective blood brain barriers. In mammals this is usually pathological in response to energetic stress. In insects a very similar process is induced by abiotic environmental stressors and can be beneficial by conserving energy. Age is a critical factor for predicting the consequences of SD in humans. We investigated the effect of aging on SD in an insect model of SD and explored the contribution of oxidative stress. Aging slowed the recovery of intact locusts from asphyxia by water submersion. In semi-intact preparations we monitored SD by recording the DC potential across the blood brain barrier in response to bath application of the Na+/K+-ATPase inhibitor, ouabain. Treatment with ouabain induced changes to the DC potential that could be separated into two distinct components: a slow, permanent negative shift, similar to the negative ultraslow potential recorded in mammals and human patients, as well as rapid, reversible negative DC shifts (SD events). Aging had no effect on the slow shift but increased the duration of SD events from ~0.6 minutes in young locusts to ~0.9 minutes in old ones. This was accompanied by a decrease in the rate of recovery of DC potential at the end of the SD event, from ~1.5 mV/s (young) to ~0.6 mV/s (old). An attempt to generate oxidative stress using rotenone was unsuccessful, but pretreatment with the antioxidant, N-acetylcysteine amide, had opposite effects to those of aging, reducing duration (control ~1.1 minutes, NACA ~0.7 minutes) and increasing rate of recovery (control ~0.5 mV/s, NACA ~1.0 mV/s) suggesting that it prevented oxidative damage occurring during the ouabain treatment. The antioxidant also reduced the rate of the slow negative shift. We propose that the aging locust nervous system is more vulnerable to stress due to a prior accumulation of oxidative damage. Our findings also strengthen the notion that insects provide useful models for the investigation of cellular and molecular mechanisms underlying SD in mammals.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cocaine taking and craving produce distinct transcriptional profiles in dopamine neurons
Dopamine (DA) signaling plays an essential role in reward valence attribution and in encoding the reinforcing properties of natural and artificial rewards. The adaptive responses from midbrain dopamine neurons to artificial rewards such as drugs of abuse are therefore important for understanding the development of substance use disorders. Drug-induced changes in gene expression are one such adaptation that can determine the activity of dopamine signaling in projection regions of the brain reward system. One of the major challenges to obtaining this understanding involves the complex cellular makeup of the brain, where each neuron population can be defined by a distinct transcriptional profile. To bridge this gap, we have adapted a virus-based method for labeling and capture of dopamine nuclei, coupled with nuclear RNA-sequencing, to study the transcriptional adaptations, specifically, of dopamine neurons in the ventral tegmental area (VTA) during cocaine taking and cocaine craving, using a mouse model of cocaine intravenous self-administration (IVSA). Our results show significant changes in gene expression across non-drug operant training, cocaine taking, and cocaine craving, highlighted by an enrichment of repressive epigenetic modifying enzyme gene expression during cocaine craving. Immunohistochemical validation further revealed an increase of H3K9me3 deposition in DA neurons during cocaine craving. These results demonstrate that cocaine-induced transcriptional adaptations in dopamine neurons vary by phase of self-administration and underscore the utility of this approach for identifying relevant phase-specific molecular targets to study the behavioral course of substance use disorders.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neuronal overexpression of potassium channel subunit Kcnn1 prolongs survival of SOD1-linked ALS and A53T alpha-synuclein mouse models
Eye muscles and the motor neurons in the innervating cranial nerve nuclei are relatively spared in human ALS, and likewise, these cranial motor neurons are spared of SOD1YFP aggregation in a transgenic mouse model of SOD1 linked ALS, G85R SOD1YFP. RNA profiling of mouse oculomotor (CN3) neurons (resistant) vs hypoglossal (CN12) and spinal cord motor neurons (susceptible) from nontransgenic mice identified differentially expressed channel and receptor genes. A number were evaluated for effects on survival of the ALS strain by transgenesis or knockout to emulate the relative RNA level in oculomotor neurons. Transgenesis of Thy1.2-driven cDNA for mouse Kcnn1, a potassium channel subunit, extended the median days of survival time to paralysis of mutant G85R SOD1YFP mice by up to 100%, associated with absence of fluorescent aggregates; extended the median time to paralysis of G93A SOD1 mice by up to 55%; and extended the median time to endstage motor disease of a Thy1.2-driven alpha-synuclein transgenic strain by up to greater than 100%. The overexpressed Kcnn1 subunit was diffusely cytoplasmic in motor neurons and found to induce a multifaceted stress response as judged by RNAseq and immunostaining, including ER stress response, mitochondrial stress response, and an integrated stress response. Like other potassium channel subunits, Kcnn1 subunit is likely targeted to the ER, but as reported earlier in rodent Kcnn1-transfected cultured cells, in the absence of Kcnn2 with which to co-assemble, Kcnn1 is channel-inactive and is diffusely cytoplasmic. Thus, a nonassembled and potentially misfolded state of overexpressed Kcnn1 targeted to the ER of neurons may explain the stress responses, which in the mutant SOD1 and A53T alpha-synuclein mice, protect against the pathogenic proteins.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Hand Position Fields of Neurons in the Premotor Cortex of Macaques during Natural Reaching
Planning and execution for goal-directed movements requires the integration of the current position of body or body parts with various kinematic parameters of the movement itself. In the hippocampus, the field-based representation of spatial information plays an essential role in this process during navigation. However, if a similar, field-based encoding framework is also utilized by the motor areas during hand reaching remains unclear. In this study, we investigated the hand position tuning in the dorsal premotor cortex (PMd) neurons (n = 601) when four monkeys performing a naturalistic reach-and-grasp task. We show that 132/601 (22%) of PMd neurons increased their firing rates when the monkey's hand occupied specific positions in the space, forming the "position fields" in their spatial firing maps that can be well described by 2D Gaussian functions/kernels. We further analyzed how the field-tuning of hand position is co-represented with other task-related parameters including the hand moving direction, speed, and reward location in the same population of PMd neurons, revealing a mixed-selective framework also similar to that discovered in the hippocampus. These position-tuned cells demonstrated high efficiency in encoding hand position, with ~10% of overall recorded neurons contributing >80% of accuracy in decoding instantaneous hand moving trajectories. These results suggest that a field-based encoding framework of position may be a common component to representing spatial information and integrating it with kinematic parameters for guiding goal-directed movements of the body or body parts.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Astrocyte regional specialization is shaped by postnatal development
Astrocytes are an abundant class of glial cells with critical roles in neural circuit assembly and function. Though many studies have uncovered significant molecular distinctions between astrocytes from different brain regions, how this regionalization unfolds over development is not fully understood. We used single-nucleus RNA sequencing to characterize the molecular diversity of brain cells across six developmental stages and four brain regions in the mouse and marmoset brain. Our analysis of over 170,000 single astrocyte nuclei revealed striking regional heterogeneity among astrocytes, particularly between telencephalic and diencephalic regions, at all developmental time points surveyed in both species. At the stages sampled, most of the region patterning was private to astrocytes and not shared with neurons or other glial types. Though astrocytes were already regionally patterned in late embryonic stages, this region-specific astrocyte gene expression signature changed dramatically over postnatal development, and its composition suggests that regional astrocytes further specialize postnatally to support their local neuronal circuits. Comparing across species, we found divergence in the expression of astrocytic region- and age-differentially expressed genes and the timing of astrocyte maturation relative to birth between mouse and marmoset, as well as hundreds of species differentially expressed genes. Finally, we used expansion microscopy to show that astrocyte morphology is largely conserved across gray matter forebrain regions in the mouse, despite substantial molecular divergence.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Anatomical and functional organization of the interpeduncular nucleus in larval zebrafish
The habenulo-interpeduncular pathway is a highly conserved neural circuit across vertebrates, but the anatomical and functional architecture of the interpeduncular nucleus (IPN) remains poorly understood. Here, we use a combination of immunohistochemistry, volumetric electron microscopy (EM), and two-photon imaging to provide the first detailed characterization of the internal organization of the IPN in larval zebrafish. We show that the IPN receives extensive projections from the tegmentum, and reveal a strict segregation between the dorsal (dIPN) and ventral (vIPN) subcircuits, with minimal cross-communication. In the dIPN, we characterise in detail the inputs and outputs of r1 pi neurons, which have been recently identified as representing the animal's heading direction. In the vIPN, we identify six distinct glomerular structures, each exhibiting specific patterns of reciprocal connections and projection pathways. Finally, we demonstrate that the connectivity and spontaneous activity patterns of habenular axons are shaped by the local anatomical features of the IPN, suggesting a role for the local interneurons in modulating presynaptic dynamics. Together, these results enhance our understanding of the internal organization of the IPN, and provide a framework for future investigations into both its physiology and its involvement in behavior.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Reduction of SynGAP-γ, disrupted splicing of Agap3, and oligodendrocyte deficits in Srrm2 mice, a genetic model of schizophrenia and neurodevelopmental disorder
Rare loss-of-function (LoF) variants in SRRM2, which encodes the SRRM2 splicing factor, are associated with schizophrenia and a neurodevelopmental disorder. How haploinsufficiency of SRRM2 leads to brain dysfunction is unknown. We find that Srrm2+/- mice display (i) large-scale changes in gene expression in neuronal and glial cells, affecting synapse-related and other common molecular pathways across multiple brain regions, (ii) reduction of multiple key postsynaptic proteins, including the gamma isoform of SynGAP, itself encoded by a neurodevelopmental disorder risk gene, (iii) abnormal splicing and elevated expression of Agap3, a SynGAP interactor, (iv) reduced numbers of oligodendrocytes accompanied by decreased expression of myelin-related mRNAs and proteins, and (v) behavioral and EEG abnormalities, including reduction in sleep spindles that phenocopy humans with schizophrenia. Our findings provide insights into the molecular and neurobiological mechanisms of and potential therapeutic avenues for schizophrenia and the SRRM2 LoF neurodevelopmental disorder.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Traveling Waves in the Human Visual Cortex: a MEG-EEG Model-Based Approach
Brain oscillations might be traveling waves propagating in cortex. Studying their propagation within single cortical areas has mostly been restricted to invasive measurements. Their investigation in healthy humans, however, requires non-invasive recordings, such as MEG or EEG. Identifying traveling waves with these techniques is challenging because source summation, volume conduction, and low signal-to-noise ratios make it difficult to localize cortical activity from sensor responses. The difficulty is compounded by the lack of a known ground truth in traveling wave experiments. Rather than source-localizing cortical responses from sensor activity, we developed a two-part model-based neuroimaging approach: (1) The putative neural sources of a propagating oscillation were modeled within primary visual cortex (V1) via retinotopic mapping from functional MRI recordings (encoding model); and (2) the modeled sources were projected onto MEG and EEG sensors to predict the resulting signal using a biophysical head model. We tested our model by comparing its predictions against the MEG-EEG signal obtained when participants viewed visual stimuli designed to elicit either fovea-to-periphery or periphery-to-fovea traveling waves or standing waves in V1, in which ground truth cortical waves could be reasonably assumed. Correlations on within-sensor phase and amplitude relations between predicted and measured data revealed good model performance. Crucially, the model predicted sensor data more accurately when the input to the model was a traveling wave going in the stimulus direction compared to when the input was a standing wave, or a traveling wave in a different direction. Furthermore, model accuracy peaked at the spatial and temporal frequency parameters of the visual stimulation. Together, our model successfully recovers traveling wave properties in cortex when they are induced by traveling waves in stimuli. This provides a sound basis for using MEG-EEG to study endogenous traveling waves in cortex and test hypothesis related with their role in cognition.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Pre-fusion AAA+ remodeling of target-SNARE protein complexes enables synaptic transmission
Membrane fusion is driven by SNARE complex formation across cellular contexts, including vesicle fusion during synaptic transmission. Multiple proteins organize trans-SNARE complex assembly and priming, leading to fusion. One target membrane SNARE, syntaxin, forms nanodomains at the active zone, and another, SNAP-25, enters non-fusogenic complexes with it. Here, we show that the AAA+ protein NSF (N-ethylmaleimide sensitive factor) and SNAP (soluble NSF attachment protein) must act prior to fusion. We show that syntaxin clusters are conserved, that NSF colocalizes with them, and characterize SNARE populations within and near these clusters using cryo-EM. Supercomplexes of NSF, alpha;-SNAP, and either a syntaxin tetramer or two binary complexes of syntaxin - SNAP-25 reveal atomic details of SNARE processing and show how sequential ATP hydrolysis drives disassembly. These results suggest a functional role for syntaxin clusters as reservoirs and a corresponding role for NSF in syntaxin liberation and SNARE protein quality control preceding fusion.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neuroanatomy of the Accessory Olfactory Bulb in the Fossorial Water Vole
The accessory olfactory bulb (AOB) plays a key role in processing chemical signals crucial for species-specific social and reproductive behaviors. While extensive research has focused on the vomeronasal system of laboratory rodents, less is known about wild species, particularly those that rely heavily on chemical communication. This study aims to characterize the morphological and neurochemical organization of the AOB in the fossorial water vole (Arvicola scherman), a subterranean rodent species from the family Cricetidae. We have employed histological techniques, including Nissl and hematoxylin staining, as well as immunohistochemical and lectin-histochemical markers, to assess the AOB structure. Our findings reveal that the AOB of the water vole exhibits a distinct laminar organization with prominent mitral cells in the mitral-plexiform layer, as well as dense labeling of periglomerular and short-axon cells in the glomerular layer. Lectin histochemistry further confirmed zonation patterns analogous to those seen in other rodent species. Immunohistochemical analysis demonstrated significant expression of PGP 9.5, suggesting its involvement in maintaining neuronal activity within the AOB. In contrast, the absence of SMI-32 labeling in the AOB, compared to its strong expression in the main olfactory bulb, highlights functional distinctions between these two olfactory subsystems. These structural and neurochemical characteristics suggest that the AOB of the fossorial water vole is adapted for enhanced processing of chemosensory signals, which may play a pivotal role in its subterranean lifestyle. Our results provide a foundation for future studies exploring the functional implications of these adaptations, including potential improvements in the integrated management of these vole populations.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Estimating the mean: behavioral and neural correlates of summary representations for time intervals
Our behavior is guided by the statistical regularities in the environment. Prior research on temporal context effects has demonstrated the dynamic processes through which humans adapt to the environment's temporal regularities. However, learning temporal regularities not only entails dynamic adaptation to traces of previous individual events but also often requires the extraction and retention of summary statistics (e.g., the mean) of temporal distributions. To investigate these summary representations for temporal distributions and to test their sensitivity to distributional changes, we explicitly asked participants to extract the mean of different distributions of time intervals, which shared the same mean but varied in their variability specifically operationalized by the width and presentation frequency of the intervals. Our findings showed that the variability of the estimated mean increased with the distributions' variability, even though the actual mean remained constant. We further examined how such learning of temporal distributions modulates EEG signals during subsequent temporal judgments. Analysis revealed that the contingent negative variation (CNV), predictive of single-trial RTs, was correlated with how much individuals' estimates of the mean were affected by the distributions' variability. Conversely, the post-interval P2 was not modulated by the distributions but predicted participants' responses, suggesting that P2 reflects the perceived duration of an interval. Taken together, our results demonstrate not only that humans can accurately estimate the mean of a temporal distribution, but also that the representation of the mean becomes more uncertain as the variability of the distribution increases, as reflected neurally in the preparation-related CNV during temporal decisions.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants
Optogenetic stimulation has become a promising approach for restoring lost body function. For example, partial restoration of vision has been achieved in a blind patient and proof-of-concept has been demonstrated for optogenetic hearing restoration in rodents. In order to prepare clinical translation of hearing restoration, efficient and safe optogenetic modification of spiral ganglion neurons (SGNs) in the mature cochlea remains to be developed. Here, we established microcatheter-based administration adeno-associated virus (AAV) to scala tympani of the cochlea of Mongolian gerbils and compared it to the previously developed AAV-injection into the spiral ganglion. We probed the potential AAV-PHP.S capsid to express channelrhodopsins (ChRs) under the control of the human synapsin promotor in mature SGNs in hearing and deafened gerbils. Using the microcatheter approach, but not with the AAV-modiolus injection, we achieved reliable ChR expression in SGN enabling optogenetic stimulation of the auditory pathway in 80% of the treated animals. Yet, the efficiency of SGN transduction was modest with only ~30% ChR-expressing SGNs. Moreover, we encountered off-target expression in hair cells in hearing gerbils in both approaches, but not ChR expression in the central nervous system using microcatheter administration. Comparing optogenetic auditory brainstem responses of gerbils with and without hair cell transduction confirmed that SGNs were the primary site of optogenetic stimulation of the pathway.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Dnajc3 (HSP40) Modulates Axon Regeneration in the Mouse Optic Nerve
The present study is designed to identify the genes modulating optic nerve regeneration in the mouse. Using the BXD mouse strains as a genetic mapping panel, we examined differential responses to axon regeneration in order to map genomic loci modulating axonal regeneration. To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adeno-associated virus (AAV) delivery of an shRNA, followed by the induction of a mild inflammatory response by an intravitreal injection of Zymosan with CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by Cholera Toxin B. Two days later, the regenerating axons within the optic nerve were examined to determine the number of regenerating axons and the distance traveled down the optic nerve. An integral genomic map was made using the regenerative response. Candidate genes were tested by knocking down expression using shRNA or by overexpressing the gene in AAV vectors. The analysis revealed a considerable amount of differential axonal regeneration across all 33 BXD strains, demonstrated by the number of axons regenerating and the length of the regenerating axons. Some strains (BXD99, BXD90, and BXD29) demonstrated significant axonal regeneration; while other strains (BXD13, BXD18, and BXD34) had very little axon regrowth. Within the regenerative data, there was a 4-fold increase in distance regenerated and a 7.5-fold difference in the number of regenerating axons. These data were used to map a quantitative trait locus modulating axonal regeneration to Chromosome 14 (115 to 119 Mb). Within this locus were 16 annotated genes. Subsequent testing revealed that one candidate gene, Dnajc3, modulates axonal regeneration. Knocking down of Dnajc3 led to a decreased regeneration response in the high regenerative strains (BXD90), while overexpression of Dnajc3 resulted in an increased regeneration response in C57BL/6J and a low regenerative strain (BXD34). In this study, Dnajc3 (encodes Heat Shock Protein 40, HSP40, a molecular chaperone) was identified as a modulator of axon regeneration in mice. Dnajc3 not only increases the number of regenerating axons, it also increases the distance the axons travel. If regeneration is to occur in large mammals, the distance that axons would have to travel to their target is considerably longer than that of the mouse. Thus, increasing the number of regenerating axons and the distance they travel may prove to be critical for functional regenerations in humans.in bioRxiv: Neuroscience on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Brain Sciences, Vol. 14, Pages 1016: Differential Resting-State Brain Characteristics of Skeleton Athletes and Non-Athletes: A Preliminary Resting-State fMRI Study
Brain Sciences, Vol. 14, Pages 1016: Differential Resting-State Brain Characteristics of Skeleton Athletes and Non-Athletes: A Preliminary Resting-State fMRI Study
Brain Sciences doi: 10.3390/brainsci14101016
Authors: Xinhong Jin Shuying Chen Yapeng Qi Qichen Zhou Jian Wang Yingying Wang Chenglin Zhou
(1) Background: This study investigates the resting-state brain characteristics of skeleton athletes compared to healthy age-matched non-athletes, using resting-state fMRI to investigate long-term skeleton-training-related changes in the brain. (2) Methods: Eleven skeleton athletes and twenty-three matched novices with no prior experience with skeleton were recruited. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity analyses were explored to investigate resting-state functional magnetic resonance imaging (rs-fMRI) data, aiming to elucidate differences in resting-state brain function between the two groups. (3) Results: Compared to the control group, skeleton athletes exhibited significantly higher ALFF in the left fusiform, left inferior temporal gyrus, right inferior frontal gyrus, left middle temporal gyrus, left and right insula, left Rolandic operculum, left inferior frontal gyrus, and left superior temporal gyrus. Skeleton athletes exhibit stronger functional connectivity in brain regions associated with cognitive and motor control (superior frontal gyrus, insula), as well as those related to reward learning (putamen), visual processing (precuneus), spatial cognition (inferior parietal), and emotional processing (amygdala), during resting-state brain function. (4) Conclusions: The study contributes to understanding how motor training history shapes skeleton athletes’ brains, which have distinct neural characteristics compared to the control population, indicating potential adaptations in brain function related to their specialized training and expertise in the sport.
in Brain Sciences on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Brain Sciences, Vol. 14, Pages 1015: Feature Contributions and Predictive Accuracy in Modeling Adolescent Daytime Sleepiness Using Machine Learning: The MeLiSA Study
Brain Sciences, Vol. 14, Pages 1015: Feature Contributions and Predictive Accuracy in Modeling Adolescent Daytime Sleepiness Using Machine Learning: The MeLiSA Study
Brain Sciences doi: 10.3390/brainsci14101015
Authors: Mohammed A. Mamun Jannatul Mawa Misti Md Emran Hasan Firoj Al-Mamun Moneerah Mohammad ALmerab Johurul Islam Mohammad Muhit David Gozal
Background: Excessive daytime sleepiness (EDS) among adolescents poses significant risks to academic performance, mental health, and overall well-being. This study examines the prevalence and risk factors of EDS in adolescents in Bangladesh and utilizes machine learning approaches to predict the risk of EDS. Methods: A cross-sectional study was conducted among 1496 adolescents using a structured questionnaire. Data were collected through a two-stage stratified cluster sampling method. Chi-square tests and logistic regression analyses were performed using SPSS. Machine learning models, including Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbors (KNN), and Gradient Boosting Machine (GBM), were employed to identify and predict EDS risk factors using Python and Google Colab. Results: The prevalence of EDS in the cohort was 11.6%. SHAP values from the CatBoost model identified self-rated health status, gender, and depression as the most significant predictors of EDS. Among the models, GBM achieved the highest accuracy (90.15%) and precision (88.81%), while CatBoost had comparable accuracy (89.48%) and the lowest log loss (0.25). ROC-AUC analysis showed that CatBoost and GBM performed robustly in distinguishing between EDS and non-EDS cases, with AUC scores of 0.86. Both models demonstrated the superior predictive performance for EDS compared to others. Conclusions: The study emphasizes the role of health and demographic factors in predicting EDS among adolescents in Bangladesh. Machine learning techniques offer valuable insights into the relative contribution of these factors, and can guide targeted interventions. Future research should include longitudinal and interventional studies in diverse settings to improve generalizability and develop effective strategies for managing EDS among adolescents.
in Brain Sciences on 2024-10-12 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Effectiveness of a multidimensional collaborative approach versus usual care in the treatment of adult depression in primary care in Chile: study protocol for a single blinded cluster randomized controlled trial [version 2; peer review: 1 approved, 1 appr
Background Major depression (MD) is a prevalent and disabling condition in Chile, with most cases being treated at the primary care level. In Chilean primary care, the authors have identified key factors associated with more complex presentations of MD and a poorer prognosis, such as a history of childhood trauma, suicidality, and comorbidities. These findings underscore the need for a multidimensional, trauma-informed, and interprofessional approach to the treatment of depression. Methods This protocol is a two-arm, single-blinded, cluster RCT to compare the effectiveness of a collaborative multidimensional approach for depression (CMAD) versus usual care to treat MD in primary care clinics in Chile. In total, 394 depressed adults from 18 to 65 years of age in twelve clinics located in Chile’s Maule Region will be consented to participate in the study. Patients and care teams from each clinic will be randomized to the intervention or to the control arm. Interprofessional teams in the intervention arm will attend 27 hours of didactic and active learning sessions focused on clinical competences to effectively engage, treat and follow up patients with the factors associated to the complex presentation of MD. Team in the control arm will receive 27 didactic sessions on current clinical guidelines for MD. Patients of both arms will be blindly assessed at baseline, three months, and six months. The primary outcome will be the reduction in depressive symptoms, with secondary outcomes including improvements in anxiety symptoms, interpersonal and social functioning, and treatment adherence. Discussion This protocol proposes the evaluation of an intervention designed to improve depression symptoms by enhancing the clinical competencies of primary care teams. These competencies are structured around collaborative care and trauma-informed practices. Trial registration NCT05016388, registered on 16 August 2021 at ClinicalTrials.gov.in F1000Research on 2024-10-11 16:39:43 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Maternal Mortality in the Governorate of Tunis between 2017 and 2023: evolution of Maternal Mortality Ratio and the main causes of death [version 1; peer review: awaiting peer review]
Background Maternal mortality is the main indicator of maternal health worldwide. The aims of your study were to determine the Maternal Mortality Ratio (MMR) in the governorate of Tunis and to identify the main causes of maternal death. Methods We included all maternal deaths between January 2017 and December 2023, reported to the Tunis Regional Health Directorate. The data collected included the MMR per 100000 live birth, sociodemographic characteristics, causes of death, circumstances of death, autopsy findings, and preventability. Results Sixty one maternal deaths were recorded. The average of MMR was 46, 88 per 100000 live births. Two peaks in the MMR were noted in 2017 and 2020. The average age of the patients was 34, 1 years (±5.1). We noted that 43, 75 % of the patients were not residents of the governorate of Tunis. The postpartum period was the most critical. In fact, 83, 33 % of maternal deaths occurred postpartum. Hemorrhage was the main etiology in 20.8% of cases. The second cause was COVID- 19complicationsin 16, 6% of cases. Conclusion This study of maternal mortality in Tunis opens the debate on the effectiveness of maternal health policies in Tunisia and the areas for improvement.in F1000Research on 2024-10-11 16:36:27 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The usefulness of a rehabilitation programme for people with stress-related disorders - A case from a rehabilitation center in Estonia. [version 1; peer review: awaiting peer review]
Background Rehabilitation programs help to improve people’s lives and reduce turnover rates in organisations. The current analysis revealed that dissatisfaction occurred among practitioners, doctors’ overlapping services, and fragmented plans. No comprehensive assessment and rehabilitation program currently exists for stress-related disorders in Estonia indicating an urgent need to conduct research and development programs for clients to reduce stress (Bugarski, Z, et al., 2016). This study research aimed to determine the usefulness of rehabilitation programs for individuals people with stress-related disorders. Method A qualitative approach was used. Methodology The sample included 10 individuals recruited from various rehabilitation centers in Estonia. Convenience sampling was used to select participants for this research. Open- and closed-ended questions were formulated using the 12 questions enclosed in this research. All transcribed interviews were formatted using the code. Extract codes within participant interviews were compared to identify similarities, differences, and closeness, and therefore formulated categories. Results The findings revealed that rehabilitation programs contribute to quality services, self-motivation, daily activities plan, self-control, recovery, attention and concentration, and coping skills, whereas traditional treatment can reduce symptoms but not change people’s lives. Conclusion This study suggests that rehabilitation programs are useful for individuals with stress disorders in the context of the Estonian healthcare system. The rehabilitation program is a useful intervention method revealed in the context of Estonia’s healthcare system, as it improves quality services, increases coping skills, self-control, and cognitive skills, and enhances recovery.in F1000Research on 2024-10-11 16:32:50 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Eosinophilia and Leucocytic DNA damage [version 1; peer review: awaiting peer review]
Eosinophilia serves as an indicator of allergy and parasite infestation. Eosinophil granules are believed to have adverse effects on cells and contribute to oxidative stress. In our current study, we investigated the relationship between eosinophilia and healthy subjects in terms of nuclear DNA damage in peripheral leukocytes. The comet assay was employed to test whole blood samples from 52 subjects in each group. The results revealed that eosinophilia subjects exhibited significantly higher levels of nuclear DNA damage in leukocytes compared to healthy subjects. Additionally, a weak positive association was observed between eosinophil counts and DNA damage. Our findings suggest that eosinophilia is linked to systemic oxidative DNA damage.in F1000Research on 2024-10-11 15:56:45 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Covid-19 mortality risk factors: Survival analysis of the hospitalized cohort in Sahloul university hospital in Tunisia [version 1; peer review: awaiting peer review]
Background Tunisia was one of the most affected nations with COVID-19 disease. The clinical features of this illness range from asymptomatic illness to death. Aim To analyse the survival of patients admitted to a Tunisian tertiary care center (Sahloul University Hospital) and identify independent predictive factors for hospital COVID-19 mortality. Methods A longitudinal study was conducted among confirmed COVID-19 patients hospitalized in Sahloul University Hospital between September 2020 and September 2022. Cox univariate regression was used to calculate the Hazard Ratio (HR) of death for patient characteristics regarding the time at risk. Risk factors with a p value of 0.2 or less in the univariate analysis were initially included in the multivariate Cox regression models. Results During the study at Sahloul Hospital, 1978 patients were hospitalized, averaging 55.65 years in age (± 21.39). Among them, 417 deaths occurred, with a median survival of 30 days (± 3.11) [23.904-36.096]. Factors significantly affecting the survival curve were: Age, male gender, comorbidities, diabetes, hypertension, endocrine diseases, obesity, intubation, and ICU admission Multilevel survival analyses revealed that hypertension (aHR 1.24; CI [1.02-1.52]; p=0.028), ICU admission (aHR 12.20- CI [9.56-15.57]; p<10-3), and male gender (HR 1.19; CI [0.98-1.46]; p=0.076) were independent factors associated with COVID-19 mortality. Conclusion Our study concluded the importance of the early identification of high-risk COVID-19 patients to decrease this virus mortality. A good understanding of the possible clinical factors associated with COVID-19 severity is helpful for clinicians in identifying patients who are at high risk and require prioritized treatment to minimize death.in F1000Research on 2024-10-11 15:53:44 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Preterm birth: associated risk factors in the tertiary care center [version 1; peer review: awaiting peer review]
The study aimed at identifying the prevalence of preterm labor and the associated risk factors. Design A quantitative approach using a retrospective case-control study. Setting Tertiary care hospital of Udupi district Karnataka. Population or Sample Women delivered in tertiary care Hospital of Udupi district, Karnataka, were the sample; among them, the cases (250) were the records of the women who had delivered before 37 weeks of gestation, and controls (500) were the records of women who delivered after 37 weeks of gestation and without any complications. Method The study was conducted using a retrospective case-control design by reviewing the case records of women who had delivered in a tertiary care hospital. Main Outcome Measures Women delivered in tertiary care Hospital of Udupi district, Karnataka, and their inpatient records were assessed for risk factors during the antenatal and delivery periods. Results The study revealed that the prevalence of preterm labor was 356 (14.86%) Out of 2402 deliveries. Among them, only 250 were assessed. It was significantly correlated with age, place of residence, degree of education, occupation, marital status, gravid para, number of deliveries, type of deliveries, gap between births, blood type, and religion. Pregnant women who had been exposed or had a risk for preterm labor included those who had been diagnosed with pregnancy-induced hypertension, medication during pregnancy, history of abortion, intense physical labor, and conception dates older than 30 years. Conclusion The preterm labor prevalence can be minimized if the modifiable risk factors are in control. Non-modifiable risk factors require keen supervision. Thus, health professionals must be alert to all modifiable and non-modifiable risk factors.in F1000Research on 2024-10-11 15:51:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Molecular docking, synthesis and preliminary evaluation of hybrid molecules of benzothiazole cross-linked with hydroxamic acid by certain linkers as HDAC inhibitors [version 1; peer review: awaiting peer review]
Background Molecular hybridization in drug design is proved to be very successful approach to provide new chemical entities with potential activities and desirable physicochemical properties. Histone deacetylases (HDACs) are involved in controlling the behavior and acetylation of histone and non-histone proteins and their inhibition causes block of cell growth, differentiation, changes in gene expression, and death. Consequently, HDAC inhibitors may lead to anticytotoxic activity. An approach of synthesizing hybrid molecules of benzothiazole cross-linked with hydroxamic acid via an amino acid or aminoalkanoic acid was considered. This approach is expected to optimize the anticytotoxic activity of the proposed compounds. Methods Hybrid molecules of benzothiazole cross-linked with hydroxamic acid (2A-E) were synthesized and their chemical structures were confirmed by spectral analyses (FT-IR, 1H-NMR and 13C-NMR). These were subjected to molecular docking on HDAC8 (PDB ID: 1T69). Computational methods were employed using the SwissADME server to predict the ADME parameters and other physicochemical properties. The cytotoxicity evaluation was performed using MTT colorimetric assay. Results Hybrids (2A-E) recorded lower ΔG (-6.322 to - 9.46) than Vorinostat (SAHA, -5.375). ΔG is an affinity scoring function (kcal/mol) and is employed to rank the candidate poses as the sum of the electrostatic and Van der Waals energies. Benzothiazole cross-linked with hydroxamic acid by a p-aminobenzoic acid (2E) has recorded the lowest docking score of -9.460 and this may refer to the possibility of high inhibitory activity. The hybrids showed no violation from Lipinski’s rule and complied with parameters with low possible passive oral absorption and no penetration into BBB. Hybrid molecules of benzothiazole recorded very interesting results, particularly, 2D and 2E which showed significant and remarkable activity. Conclusions Hybrid molecules of benzothiazole cross-linked with hydroxamic acid recorded very interesting results, particularly, compounds 2D and 2E which showed significant and remarkable activity on lung cancer cell line type A549.in F1000Research on 2024-10-11 15:38:35 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
An Insight into developmental changes in reasoning skills among Indian Preschoolers: A cross-sectional study using a story-based approach [version 3; peer review: 1 approved, 1 approved with reservations]
Background: Considering the importance of exploring the development of reasoning skills during preschool period and the suitability of using a culturally linguistically relevant story-based approach for the same, the present research intended to profile the reasoning skills in typically developing Indian preschool children between 36 and 72 months using a story-based approach. The specific objectives were to develop explanation, prediction, and inference based reasoning tasks around a story and assess the reasoning skills in typically developing Indian preschool children using the same. Method: Reasoning tasks across explanation, prediction, and inference domains were developed based on a story and evaluated for its psychometric properties. The developed tasks were then administered to 63 typically developing Indian preschool children attending English medium schools in Mangalore. The preschoolers were equally divided into three age groups, and the responses obtained across the age groups were analyzed quantitatively and qualitatively. Results: The developed tasks were confirmed to have good psychometric properties like content validity and reliability. The age comparisons of reasoning abilities using one-way ANOVA suggested an increase in reasoning abilities with age during the preschool period. The qualitative analysis further suggested that with increasing age, the nature of reasoning changed from content-based reasoning to reasoning based on prior knowledge which was integrated with the story content. Conclusion: The study describes reasoning skill development using a story-based task in Indian preschoolers. The study findings further provide clinical and educational implications to assess and foster reasoning abilities among preschoolers.in F1000Research on 2024-10-11 15:35:54 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Enhancing Academic Success: A mixed Study on the Influencing Factors among Pharmacy Students in Syrian Universities [version 2; peer review: 2 approved with reservations]
Background Academic achievement is the result of both effort and perseverance exerted by the students. This mixed-methods study aims to investigate the factors affecting the academic achievement of pharmacy students in Syrian universities. Methods A convergent parallel mixed-methods study was utilized. In the quantitative phase, a cross-sectional study was conducted on 1008 students (773 females and 235 males) from 23 Syrian universities. A questionnaire consisting of 48 items was designed to be completed by pharmacy students using a 5-point Likert scale. In the qualitative phase, twelve questions were developed to interview thirty pharmacy students from five Syrian universities to obtain in-depth insights into the factors influencing their academic achievement. Results A significant number of students lacked effective time management skills, identified as a weakness among students. The majority of students faced challenges in maintaining a consistent study routine, averaging a score of (2.0). Motivation towards learning emerged as a crucial factor in enhancing academic performance. Lecturers in the pharmacy faculty employed traditional teaching methods (2.01), and the pharmacy curriculum was perceived as lacking modernity (1.92). Quantitative findings demonstrated that pharmacy students experienced exam-related anxiety (2.05), identified as a weakness in the qualitative phase. Factors associated with the Syrian crisis, like unreliable electricity (1.87) and transportation issues (1.83), could have an impact on academic achievement. Economic conditions were identified as challenging to students’ academic performance, negatively affecting the learning process (1.98). Conclusion The results of the study demonstrate that personal factors, lecturers, educational environment, exams, and the Syrian crisis influence the academic achievement of pharmacy students in Syrian universities.in F1000Research on 2024-10-11 15:25:32 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Effectiveness of Play Therapy Programme in Promoting Early Child Development of under-5 Children visiting Tertiary Care Hospital in Rural Settings: Study Protocol of a Randomized Controlled Trial. [version 2; peer review: 1 approved with reservations]
Background Good care and conscious, mindful parenting are the essential requirements of the early childhood period. Good care in early childhood consists of mindful handling of children’s needs like hunger, care in sickness, socio-emotional needs, safety, love and affection. Good care promotes children’s development and provides a favourable environment for learning. It’s a well-known fact that hospitalization is a stressful situation for child of any age. Play is an integral part of early childhood period which is virtually restricted in hospital settings. This study will try to explore the effectiveness of play therapy delivered in hospital settings, on early child development. Methods This will be a randomized control trial conducted in the Paediatrics department of a tertiary care hospital in Wardha, India. The sample size will be 360 children, 180 each in intervention and control arm. The hospitalized children from intervention arm will receive customized Play Therapy sessions from trained research assistants and will be followed up at scheduled home visits for one year from the date of enrolment. All children will be assessed for changes in cognitive, motor and socio-emotional development scores. The differences in development scores between intervention and control groups will be compared and effect sizes of changes will be calculated. Discussion Implementation of play stimulation activities have been reported as useful strategies for promoting child development and good recovery during hospitalization. This trial will attempt to explore the effectiveness of play therapy on changes in child development scores of children from intervention group compared to the control group. The customized play therapy program will be adapted to paediatric inpatient settings, and attempts will be made to improve the Play Therapy kit for hospitalized children. Registration Clinical Trial Registry of India Registration No.: C.T.R.I./2022/03/041355, dated 24/03/2022. Protocol Version: v6 Dated 04/10/2024.in F1000Research on 2024-10-11 15:13:52 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Case Report: Delayed Diagnosis of Leprosy-Related Neuropathic Ulcer, Insights from a Case of Delay to Diagnose across Four Clinical Settings [version 1; peer review: awaiting peer review]
Background Neuropathy is common in both Diabetes Mellitus (DM) and Leprosy, often resulting in neuropathic ulcers. Leprosy-related neuropathic ulcers are frequently misdiagnosed as DM-related, causing delays in appropriate care. This case report underscores the importance of timely recognition and a better understanding of Leprosy-related neuropathic ulcers to prevent misdiagnosis and improve patient outcomes. Methods The case report adopt the CARE Guidelines and was conducted at the Wound Care Specialist Clinic, Griya Afiat, Makassar, East Indonesia. Data were collected using a Minimum Data Sheet (MDS) to capture demographics, health history, and history of treatments. A head-to-toe assessment focused on the eyes, hands, and feet, with neuropathy, confirmed using the Semmes Weinstein Monofilament test, and angiopathy was assessed by palpating the dorsal pedis and posterior tibialis pulse. Wound care interventions consisted of cleansing, debridement, and dressing. Given the similarities between Leprosy-related neuropathic ulcers and DM-related neuropathic ulcers, the DMIST (depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunnelling/undermining) tool was used to evaluate wound healing progress. Results Anamnesis indicated patient has no DM, with normal blood glucose; however, the patient had neuropathic wounds on her feet, asymmetrical eyebrow distribution, and rashes on her hands and calves, with neuropathy confirmed by a monofilament test—initial treatment involved Cadexomer Iodine powder to control bacterial growth and Honey-based gel to promote granulation. Over 62 days, 11 treatments were administered, with an average dressing change every 5.6 days, which improved the DMIST score from 12 to 4 by the end of observation day. Conclusions This case report highlights the significance of distinguishing leprosy-related neuropathic ulcers from those associated with DM to ensure accurate diagnosis and timely treatment. By employing comprehensive assessment tools and targeted wound care interventions, significant improvements in wound healing were achieved, emphasizing the need for greater awareness and clinical vigilance in managing Leprosy-related neuropathic ulcers.in F1000Research on 2024-10-11 15:12:39 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Trends of machine learning for dental caries research in Southeast Asia: insights from a bibliometric analysis [version 3; peer review: 2 approved with reservations]
Background Dental caries is a common chronic oral disease, posing a serious public health issue. By analyzing large datasets, machine learning shows potential in addressing this problem. This study employs bibliometric analysis to explore emerging topics, collaborations, key authors, and research trends in Southeast Asia related to the application of machine learning in dental caries management. Methods A comprehensive selection using the Scopus database to obtain relevant research, covering publications from inception to July 2024 was done. We employed the Bibliometric approaches, including co-authorship networks, yearly publishing trends, institutional and national partnerships, keyword co-occurrence analysis, and citation analysis, for the collected data. To explore the visualization and network analysis, we employed the tools such as VOSviewer and Bibliometrix in R package. Results The final bibliometric analysis included 246 papers. We found that Malaysia became the top contributor with 59 publications, followed by Indonesia (37) and Thailand (29). Malaysia had the highest Multiple Country Publications (MCP) ratio at 0.407. Top institutions including the Universiti Sains Malaysia led with 39 articles, followed by Chiang Mai University (36) and the National University of Singapore (30) became the leader. Co-authorship analysis using VOSviewer revealed six distinct clusters. A total of 1220 scholars contributed to these publications. The top 10 keywords, including ‘human’ and ‘dental caries,’ indicated research hotspots. Conclusion We found growing evidence of machine learning applications to address dental caries in Southeast Asia. The bibliometric analysis highlights key authors, collaborative networks, and emerging topics, revealing research trends since 2014. This study underscores the importance of bibliometric analysis in tackling this public health issue.in F1000Research on 2024-10-11 14:26:34 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Bayesian inference of state feedback control parameters for fo perturbation responses in cerebellar ataxia
by Jessica L. Gaines, Kwang S. Kim, Ben Parrell, Vikram Ramanarayanan, Alvincé L. Pongos, Srikantan S. Nagarajan, John F. Houde
Behavioral speech tasks have been widely used to understand the mechanisms of speech motor control in typical speakers as well as in various clinical populations. However, determining which neural functions differ between typical speakers and clinical populations based on behavioral data alone is difficult because multiple mechanisms may lead to the same behavioral differences. For example, individuals with cerebellar ataxia (CA) produce atypically large compensatory responses to pitch perturbations in their auditory feedback, compared to typical speakers, but this pattern could have many explanations. Here, computational modeling techniques were used to address this challenge. Bayesian inference was used to fit a state feedback control (SFC) model of voice fundamental frequency (fo) control to the behavioral pitch perturbation responses of speakers with CA and typical speakers. This fitting process resulted in estimates of posterior likelihood distributions for five model parameters (sensory feedback delays, absolute and relative levels of auditory and somatosensory feedback noise, and controller gain), which were compared between the two groups. Results suggest that the speakers with CA may proportionally weight auditory and somatosensory feedback differently from typical speakers. Specifically, the CA group showed a greater relative sensitivity to auditory feedback than the control group. There were also large group differences in the controller gain parameter, suggesting increased motor output responses to target errors in the CA group. These modeling results generate hypotheses about how CA may affect the speech motor system, which could help guide future empirical investigations in CA. This study also demonstrates the overall proof-of-principle of using this Bayesian inference approach to understand behavioral speech data in terms of interpretable parameters of speech motor control models.in PLoS Computational Biology on 2024-10-11 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Unleashing the cardioprotective potential of Ezetimibe against Doxorubicin-induced cardiotoxicity in Wistar rats: Targeting oxidative stress and NF-κB-mediated inflammation [version 1; peer review: awaiting peer review]
Background Doxorubicin (DOX) is a potent antineoplastic agent used in treating various adult and pediatric cancers, but it tends to provoke dose-dependent cardiotoxicity. Ezetimibe (EZE), a cholesterol-lowering drug, has been reported to possess defensive actions against oxidative stress and inflammation, which are two of the main proposed mechanisms underlying the development of DOX-induced cardiotoxicity (DIC), hence, we aimed to inspect the possible protective effect of EZE against DIC in rats. Methods 24 adult male Wistar rats were allocated into four groups of six: control, DOX, 10 mg/kg EZE plus DOX and 20 mg/kg EZE plus DOX. At the end of the study, the experimental rats were anesthetized and blood samples were collected for biochemical analysis, after which the hearts were excised and heart tissue samples were obtained for biochemical and gene expression analyses. Results Pretreatment with EZE at a dose of 10 or 20 mg/kg alleviated cardiac damage induced by DOX, as EZE blunted the rise in serum levels of cardiac injury biomarkers, including cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Additionally, pretreating rats with EZE at either dose mitigated DOX-induced oxidative stress by elevating the levels of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), with consequent reduction in the lipid peroxidation biomarker malondialdehyde (MDA) in cardiac tissues. Furthermore, pretreatment with either dose of EZE hindered DOX-mediated inflammation, where EZE suppressed cardiac nuclear factor-kappa B (NF-κB) signaling and negatively regulated the gene expression of its downstream proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) with either dose and interleukin-1 beta (IL-1β) with the higher one. Conclusions Our findings indicate that EZE exhibited cardioprotection against DIC in rats, which makes EZE an interesting area for further investigations, animal- and human-wise, that can pave the way for a potential clinical application in preventing DIC in the future.in F1000Research on 2024-10-11 11:56:21 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Reliability, validity, and minimal clinically important differences for the Thai-version of the Aberdeen Varicose Vein Questionnaire (AVVQ-Thai) in patients with chronic venous disease [version 2; peer review: 1 approved, 1 approved with reservations]
Background Patient-reported outcome measures (PROMs) are essential for assessing the health of patients with chronic venous disease (CVD). Therefore, we aimed to translate the Aberdeen Varicose Vein Questionnaire into Thai language (AVVQ-Thai) and evaluate its reliability and validity. Minimal clinically important differences (MCID) of the AVVQ-Thai also be estimated. Methods International standards for PROM translation were followed including the forward-backwards translation of the AVVQ. Patients with Clinical-Etiology-Anatomy-Pathophysiology (CEAP) C2-C6 with truncal reflux were prospectively included. Venous interventions were used to treat reflux and varicosities. Patients’ characteristics, venous clinical severity scores (VCSS), EuroQol EQ-5D, and AVVQ-Thai were collected pre- and one-month post-intervention. AVVQ-Thai was also collected one to two weeks after the initial visit by reply-paid postal questionnaire. Results The study included 119 patients (30% C2, 29% C3, 28% C4, 11% C5, and 2% C6). The AVVQ-Thai had good internal consistency with Cronbach’s alpha of 0.783 and moderate reliability with the intraclass correlation coefficient of 0.67 (95%CI: 0.50, 0.79). The AVVQ-Thai was significantly correlated with VCSS and was able to discriminate patients with different levels of health problems as assessed by EQ-5D at both pre-and post-intervention, demonstrating good construct and discriminative validity. The median AVVQ scores improved significantly after intervention from 15.4 (IQR 8.3, 24.2) to 4.2 (IQR 1.3, 8.4) in C2-C3, and 18.9 (IQR 14.1, 25.5) to 7.3 (IQR 4.6, 16.3) in C4-C6. The MCID of the AVVQ was 6.21 on the 0-100 scale, which equates to the level of difference necessary to be clinically meaningful. Conclusions AVVQ-Thai has satisfactory evidence for internal consistency, reliability, validity, and responsiveness to change and is recommended for application in Thailand.in F1000Research on 2024-10-11 11:31:05 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Temporal variability and cell mechanics control robustness in mammalian embryogenesis
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Hidden comet tails of marine snow impede ocean-based carbon sequestration
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Environmental and societal consequences of winter ice loss from lakes
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Drivers of woody dominance across global drylands
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Mechanism of degrader-targeted protein ubiquitinability
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Who owns reefer vessels? Uncovering the ecosystem of transshipment in fisheries
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The role of an oxidized lithospheric mantle in gold mobilization
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Perihatch surge of thyroid hormone drives cognitive flexibility in newborn chicks
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Primitive asteroids as a major source of terrestrial volatiles
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A global poleward shift of atmospheric rivers
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Predicting rapid adaptation in time from adaptation in space: A 30-year field experiment in marine snails
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Dephosphorylation and ion binding in prokaryotic calcium transport
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
CLIC5 promotes myoblast differentiation and skeletal muscle regeneration via the BGN-mediated canonical Wnt/β-catenin signaling pathway
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Self-healable and stretchable perovskite-elastomer gas-solid triboelectric nanogenerator for gesture recognition and gripper sensing
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Nonlinearity-enhanced continuous microwave detection based on stochastic resonance
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer’s disease
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Generalized contact matrices allow integrating socioeconomic variables into epidemic models
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Shank3 mutation impairs glutamate signaling and myelination in ASD mouse model and human iPSC-derived OPCs
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A pyroxene-based quantum magnet with multiple magnetization plateaus
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Attentional guidance through object associations in visual cortex
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Erratum for the Research Article: “Epidemic outcomes following government responses to COVID-19: Insights from nearly 100,000 models”
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-11 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Mechanical Thrombectomy for Pediatric Stroke: Focal Cerebral Arteriopathy Versus Cardioembolic Etiologies—Pooled Analysis of the Save ChildS and KidClot Cohort
Background
The study aimed to compare outcomes of mechanical thrombectomy (MT) in pediatric patients with acute ischemic stroke (AIS) caused by focal cerebral arteriopathy (FCA) versus cardioembolism (CE).
Methods
Data from the Save ChildS and KidClot cohorts were merged. Children with AIS because of FCA or CE that underwent MT were included. The study used the Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation (CASCADE) for stroke cause assessment. Descriptive statistics and multivariable regression models were used to analyze final modified thrombolysis in cerebral infarction (mTICI) scores, periprocedural complications, and functional outcomes assessed by the modified Rankin scale (mRS) at 6 to 12 months.
Results
The analysis included 60 children with 14 FCA and 46 CE cases. CE etiology was associated with better revascularization (good to excellent thrombolysis in cerebral infarction scores) and shift toward better outcomes (common adjusted odds ratio of mRs for CE vs FCA: 0.27, 95% CI: [0.06–0.97], p = 0.039), with no difference in favorable outcome rates. FCA was associated with significantly lower rates of excellent revascularization (21% vs 65%, p < 0.001). No difference in complications' rates was observed between the groups (7.2% in FCA vs 5.5%, p = 0.69).
Interpretation
We found that pediatric AIS because of CE etiology has more favorable procedural outcomes compared to FCA following MT. This translated to mixed functional outcomes that may be more favorable in the CE group. These findings highlight the need for further research to refine treatment protocols for pediatric stroke, particularly in understanding and managing FCA in children. ANN NEUROL 2024
in Annals of Neurology on 2024-10-11 04:18:54 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Advanced MRI Measures of Myelin and Axon Volume Identify Repair in Multiple Sclerosis
Objective
Pathological studies suggest that multiple sclerosis (MS) lesions endure multiple waves of damage and repair; however, the dynamics and characteristics of these processes are poorly understood in patients living with MS.
Methods
We studied 128 MS patients (75 relapsing–remitting, 53 progressive) and 72 healthy controls who underwent advanced magnetic resonance imaging and clinical examination at baseline and 2 years later. Magnetization transfer saturation and multi-shell diffusion imaging were used to quantify longitudinal changes in myelin and axon volumes within MS lesions. Lesions were grouped into 4 classes (repair, damage, mixed repair damage, and stable). The frequency of each class was correlated to clinical measures, demographic characteristics, and levels of serum neurofilament light chain (sNfL).
Results
Stable lesions were the most frequent (n = 2,276; 44%), followed by lesions with patterns of “repair” (n = 1,352; 26.2%) and damage (n = 1,214; 23.5%). The frequency of “repair” lesion was negatively associated with disability (β = −0.04; p < 0.001) and sNfL (β = −0.16; p < 0.001) at follow-up. The frequency of the “damage” class was higher in progressive than relapsing–remitting patients (p < 0.05) and was related to disability (baseline: β = −0.078; follow-up: β = −0.076; p < 0.001) and age (baseline: β = −0.078; p < 0.001). Stable lesions were more frequent in relapsing–remitting than in progressive patients (p < 0.05), and in younger patients versus older (β = −0.07; p < 0.001) at baseline. Further, “mixed” lesions were most frequent in older patients (β = 0.004; p < 0.001) at baseline.
Interpretation
These findings show that repair and damage processes within MS lesions occur across the entire disease spectrum and that their frequency correlates with patients disability, age, disease duration, and extent of neuroaxonal damage. ANN NEUROL 2024
in Annals of Neurology on 2024-10-11 04:18:28 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS
Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report “Living with ALS,” recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024
in Annals of Neurology on 2024-10-11 04:14:23 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Waste clearance shapes aging brain health
Jiang-Xie et al. review how fluid flow dynamics in the brain, crucial for waste clearance, deteriorate with age, contributing to neurodegenerative diseases. They highlight potential therapeutic strategies targeting these systems to preserve cognitive function and brain health during aging.in Neuron: In press on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
OLFM4 regulates the antimicrobial and DNA binding activity of neutrophil cationic proteins
Neutrophil cationic proteins (NCPs) have antibacterial, pro-inflammatory, and tissue repair properties. Vandenberghe-Dürr et al. show that OLFM4, a negatively charged granule molecule, disrupts NCP functions, impairing bacterial clearance and skin wound repair. Inhibiting OLFM4 therefore represents an attractive therapeutic strategy to accelerate skin wound closure.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
DNA methylation activates retron Ec86 filaments for antiphage defense
Wang et al. show that a phage-encoded DNA cytosine methyltransferase triggers the retron Ec86 system by directly methylating msDNA. They also solved the structure of the Ec86-effector filament containing NAD+ hydrolysis products and demonstrated that the filament is capable of hydrolyzing NAD(P)+, providing insights into Ec86’s antiphage defense mechanism.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The medial entorhinal cortex encodes multisensory spatial information
Nguyen et al. showed how the medial entorhinal cortex uses distinct cognitive maps to represent auditory and visual spatial information, both of which guide successful navigation. This representation involves "unimodality cells" recruited by a specific sensory modality and "multimodality cells" displaying different activity patterns across the two sensory modalities.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Extracellular vesicles from neural stem cells safeguard neurons in intracerebral hemorrhage by suppressing reactive astrocyte neurotoxicity
Li et al. demonstrate that EVs-NSC attenuate neurotoxic astrocyte activation in mice with ICH and in human astrocyte models. They identify IFNβ as a key driver of neurotoxic astrocytes and show that miR-124-3p within EVs-NSC reduces astrocyte-mediated neurotoxicity by simultaneously targeting IFNβ and ELOVL1, offering a promising ICH therapy.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
LTP expression mediated by autonomous activity of GluN2B-bound CaMKII
Rumian et al. demonstrate that enzymatic activity of CaMKII is not required for LTP induction or maintenance but is required for the intermediary phase of LTP expression. CaMKII pT286 was required only during LTP induction, whereas LTP expression was instead mediated by the autonomous activity of GluN2B-bound CaMKII.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neuronal lineage tracing from progenitors in human cortical organoids reveals mechanisms of neuronal production, diversity, and disease
Bury et al. utilize genetic lineage tracing to determine the progenitor lineage of neurons in human cortical organoids. They find most glutamatergic neurons are produced through intermediate progenitors, similar neurons from different progenitor lineages are transcriptionally distinct, and ASD-patient-derived genetic variants alter the proportion and transcriptional profile of lineage-specific groups.in Cell Reports: Current Issue on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Regulatory genome annotation of 33 insect species
Annotation of newly sequenced genomes frequently includes genes, but rarely covers important non-coding genomic features such as the cis-regulatory modules—e.g., enhancers and silencers—that regulate gene expression. Here, we begin to remedy this situation by developing a workflow for rapid initial annotation of insect regulatory sequences, and provide a searchable database resource with enhancer predictions for 33 genomes. Using our previously developed SCRMshaw computational enhancer prediction method, we predict over 2.8 million regulatory sequences along with the tissues where they are expected to be active, in a set of insect species ranging over 360 million years of evolution. Extensive analysis and validation of the data provides several lines of evidence suggesting that we achieve a high true-positive rate for enhancer prediction. One, we show that our predictions target specific loci, rather than random genomic locations. Two, we predict enhancers in orthologous loci across a diverged set of species to a significantly higher degree than random expectation would allow. Three, we demonstrate that our predictions are highly enriched for regions of accessible chromatin. Four, we achieve a validation rate in excess of 70% using in vivo reporter gene assays. As we continue to annotate both new tissues and new species, our regulatory annotation resource will provide a rich source of data for the research community and will have utility for both small-scale (single gene, single species) and large-scale (many genes, many species) studies of gene regulation. In particular, the ability to search for functionally related regulatory elements in orthologous loci should greatly facilitate studies of enhancer evolution even among distantly related species.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Heterozygous expression of a Kcnt1 gain-of-function variant has differential effects on somatostatin- and parvalbumin-expressing cortical GABAergic neurons
More than 20 recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (KNa) channel gene KCNT1 in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a Kcnt1 GOF variant (Kcnt1Y777H) on KNa currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant KCNT1 GOF variants in DEEs. Although the Kcnt1Y777H variant had no effects on glutamatergic or VIP neuron function, it increased subthreshold KNa currents in both SST and PV neurons but with opposite effects on neuronal output; SST neurons became hypoexcitable with a higher rheobase current and lower action potential (AP) firing frequency, whereas PV neurons became hyperexcitable with a lower rheobase current and higher AP firing frequency. Further neurophysiological and computational modeling experiments showed that the differential effects of the Kcnt1Y777H variant on SST and PV neurons are not likely due to inherent differences in these neuron types, but to an increased persistent sodium current in PV, but not SST, neurons. The Kcnt1Y777H variant also increased excitatory input onto, and chemical and electrical synaptic connectivity between, SST neurons. Together, these data suggest differential pathogenic mechanisms, both direct and compensatory, contribute to disease phenotypes, and provide a salient example of how a pathogenic ion channel variant can cause opposite functional effects in closely related neuron subtypes due to interactions with other ionic conductances.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling
Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma, and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested tongue swelling formation. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Genome-wide mapping of native co-localized G4s and R-loops in living cells
The interplay between G4s and R-loops are emerging in regulating DNA repair, replication, and transcription. A comprehensive picture of native co-localized G4s and R-loops in living cells is currently lacking. Here, we describe the development of HepG4-seq and an optimized HBD-seq methods, which robustly capture native G4s and R-loops, respectively, in living cells. We successfully employed these methods to establish comprehensive maps of native co-localized G4s and R-loops in human HEK293 cells and mouse embryonic stem cells (mESCs). We discovered that co-localized G4s and R-loops are dynamically altered in a cell type-dependent manner and are largely localized at active promoters and enhancers of transcriptional active genes. We further demonstrated the helicase Dhx9 as a direct and major regulator that modulates the formation and resolution of co-localized G4s and R-loops. Depletion of Dhx9 impaired the self-renewal and differentiation capacities of mESCs by altering the transcription of co-localized G4s and R-loops -associated genes. Taken together, our work established that the endogenous co-localized G4s and R-loops are prevalently persisted in the regulatory regions of active genes and are involved in the transcriptional regulation of their linked genes, opening the door for exploring broader roles of co-localized G4s and R-loops in development and disease.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Systematic evaluation of multifactorial causal associations for Alzheimer’s disease and an interactive platform MRAD developed based on Mendelian randomization analysis
Alzheimer’s disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify various classes of risk or protective factors for AD, early-onset AD, and late-onset AD. We generated 400,274 data entries in total, among which the major analysis method of the IVW model consists of 73,129 records with 4840 exposure traits, which fall into 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait. More importantly, a freely accessed online platform called MRAD (https://gwasmrad.com/mrad/) has been developed using the Shiny package with MR analysis results. Additionally, novel potential AD therapeutic targets (CD33, TBCA, VPS29, GNAI3, PSME1) are identified, among which CD33 was positively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. TBCA and VPS29 were negatively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. GNAI3 and PSME1 were negatively associated with the main outcome traits of AD, as well as with LOAD, but had no significant causal association with EOAD. The findings of our research advance our understanding of the etiology of AD.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Transcriptional inhibition after irradiation occurs preferentially at highly expressed genes in a manner dependent on cell cycle progression
In response to DNA double-strand damage, ongoing transcription is inhibited to facilitate accurate DNA repair while transcriptional recovery occurs after DNA repair is complete. However, the mechanisms at play and the identity of the transcripts being regulated in this manner are unclear. In contrast to the situation following UV damage, we found that transcriptional recovery after ionizing radiation (IR) occurs in a manner independent of the HIRA histone chaperone. Sequencing of the nascent transcripts identified a programmed transcriptional response, where certain transcripts and pathways are rapidly downregulated after IR, while other transcripts and pathways are upregulated. Specifically, most of the loss of nascent transcripts occurring after IR is due to inhibition of transcriptional initiation of the highly transcribed histone genes and the rDNA. To identify factors responsible for transcriptional inhibition after IR in an unbiased manner, we performed a whole genome gRNA library CRISPR/Cas9 screen. Many of the top hits on our screen were factors required for protein neddylation. However, at short times after inhibition of neddylation, transcriptional inhibition still occurred after IR, even though neddylation was effectively inhibited. Persistent inhibition of neddylation blocked transcriptional inhibition after IR, and it also leads to cell cycle arrest. Indeed, we uncovered that many inhibitors and conditions that lead to cell cycle arrest in G1 or G2 phase also prevent transcriptional inhibition after IR. As such, it appears that transcriptional inhibition after IR occurs preferentially at highly expressed genes in cycling cells.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices
Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling.in eLife on 2024-10-11 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Sense of Agency during Encoding Predicts Subjective Reliving
Autonoetic consciousness (ANC), the ability to re-experience personal past events links episodic memory and self-consciousness by bridging awareness of oneself in a past event (i.e., during its encoding) with awareness of oneself in the present (i.e., during the reliving of a past event). Recent neuroscience research revealed a bodily form of self-consciousness, including the sense of agency (SoA) and the sense of body ownership (SoO) that are based on the integration of multisensory bodily inputs and motor signals. However, the relation between SoA and/or SoO with ANC is not known. Here, we used immersive virtual reality technology and motion tracking and investigated the potential association of SoA/SoO with ANC. For this, we exposed participants to different levels of visuomotor and perspectival congruency, known to modulate SoA and SoO, during the encoding of virtual scenes and collected ANC ratings 1 week after the encoding session. In a total of 74 healthy participants, we successfully induced systematic changes in SoA and SoO during encoding and found that ANC depended on the level of SoA experienced during encoding. Moreover, ANC was positively associated with SoA, but only for the scene encoded with preserved visuomotor and perspectival congruency, and such SoA–ANC coupling was absent for SoO and control questions. Collectively, these data provide behavioral evidence in a novel paradigm that links a key subjective component of bodily self-consciousness during encoding, SoA, to the subjective reliving of those encoded events from one's past, ANC.
in eNeuro on 2024-10-10 16:30:22 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Role of the Nucleus Accumbens in Signaled Avoidance Actions
Animals, humans included, navigate their environments guided by sensory cues, responding adaptively to potential dangers and rewards. Avoidance behaviors serve as adaptive strategies in the face of signaled threats, but the neural mechanisms orchestrating these behaviors remain elusive. Current circuit models of avoidance behaviors indicate that the nucleus accumbens (NAc) in the ventral striatum plays a key role in signaled avoidance behaviors, but the nature of this engagement is unclear. Evolving perspectives propose the NAc as a pivotal hub for action selection, integrating cognitive and affective information to heighten the efficiency of both appetitive and aversive motivated behaviors. To unravel the engagement of the NAc during active and passive avoidance, we used calcium imaging fiber photometry to examine NAc GABAergic neuron activity in ad libitum moving mice performing avoidance behaviors. We then probed the functional significance of NAc neurons using optogenetics and genetically targeted or electrolytic lesions. We found that NAc neurons code contraversive orienting movements and avoidance actions. However, direct optogenetic inhibition or lesions of NAc neurons did not impair active or passive avoidance behaviors, challenging the notion of their purported pivotal role in adaptive avoidance. The findings emphasize that while the NAc encodes avoidance movements, it is not required for avoidance behaviors, highlighting the distinction between behavior encoding or representation and mediation or generation.
in eNeuro on 2024-10-10 16:30:22 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Primary health care as the main guarantor of a healthy population in the country and a global challenge in the world: a systematic review [version 2; peer review: 1 approved with reservations, 1 not approved]
Background Primary health care (PHC) is a fundamental aspect of healthcare systems globally, playing a crucial role in maintaining the health of the population. Despite its importance, there are still gaps in the delivery of PHC services. This study aims to analyze the healthcare system and the existing gaps to develop strategies for improving PHC services. Methods This study is a mixed method a combination of documentary analysis and narrative synthesis as an alternative to meta-analysis. For our systematic review, we primarily focused on articles published within the last 10 years. However, we also included some older articles (published between 2003 and 2009) that provided valuable insights into the historical context and evolution of primary healthcare systems. Data of each article reviewed during the review - Study, Article, Study setting, Study design, Study assessment, Study suggestions are presented in Table 1. A total of 38 articles were reviewed. The data sources include peer-reviewed articles and other relevant literature on PHC services. With appropriate keywords. Results The study identifies gaps in PHC services, including issues with access to care, affordability, and quality of care. It provides insights into the challenges faced by PHC systems worldwide, highlighting the need for strategies to address these issues. Conclusions The study contributes to a better understanding of the challenges faced by PHC systems worldwide and provides insights for policymakers and healthcare providers to improve healthcare services. The systematic review, which focuses on PHC, was conducted following the PRISMA guidelines. The PRISMA diagram of study selection was used to illustrate the process of article inclusion and exclusion. Table 1 provides a summary of the key information from the selected articles.in F1000Research on 2024-10-10 15:02:14 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The development of novel score model as a predictor of in-hospital mortality of adult cardiac surgery patients in Indonesia [version 1; peer review: awaiting peer review]
Introduction In recent years, the number of cardiac surgeries has been on the rise. Several predictive models have been developed to assess the risk of mortality for these patients. EuroSCORE II, a widely used model, demonstrates good discrimination and calibration for the European population, but its accuracy may vary in the Indonesian population. The purpose of this study was to develop a scoring model tailored to Indonesian population, which may have better accuracy in assessing in-hospital mortality risk among adult cardiac surgery patients. Method A retrospective study was conducted using medical records of adult cardiac surgery patients from four participating hospitals. Potential risk factors were included as variables and analyzed using bivariate and multivariable logistic regression with the L-backward method. Bootstrapping was applied to enhance the model’s validity. Receiver operating characteristic (ROC) curves were created for each model, and the area under the curve (AUC) was calculated to assess discrimination ability, while the Hosmer-Lemeshow test was used to evaluate calibration. Results We extracted data from 4,875 patients, with a mean age of 50.41 years, and most patients were men (63.1%). The majority of patients were in NYHA class I-II. The in-hospital mortality rate was 6.5%. From 62 potential variables, 13 variables were included in the final model. Our new model demonstrated strong discrimination and calibration (AUC 0.7564; Hosmer-Lemeshow p = 0.9510). Conclusion The newly developed scoring model exhibited good discrimination and calibration, making it a promising tool for predicting in-hospital mortality in adult cardiac surgery patients in Indonesia.in F1000Research on 2024-10-10 14:42:53 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Building resilience of the Ghanaian healthcare system: Lessons from a global health stage: Preparedness for the next pandemic: A scoping review [version 1; peer review: awaiting peer review]
Background The coronavirus disease (COVID-19) pandemic has underscored the need for resilient health systems. However, Ghana does not seem to achieve commensurate results, suggesting potential gaps in critical interventions. This study examines these gaps by drawing on global experiences to guide Ghana's preparedness for future emergencies. Methods A scoping review based on the synthesis of published journal articles and grey literature was used to gather relevant evidence to address the study’s objective. Peer-reviewed literature searches were conducted in databases, including Medline, Scopus, and Health Sources, supplemented by searches on organizational websites to identify grey literature. We adopted the Organization for Economic Co-operation and Development (OECD) framework to explore how health systems responded to the COVID-19 pandemic globally and draw lessons for strengthening Ghana's health system resilience. We analyzed policy responses in three main areas: pandemic preparedness, crisis management, and response and recovery. Results Ten strategies emerged from the study as critical in strengthening health system resilience against future pandemics. These strategies include whole-of-government engagement, financing for preparedness, community engagement and trust, robust surveillance systems, emergency medical care, diverse workforce development, digital health integration, critical health infrastructure, well-planned commodities/products, and social capital. Each strategy plays a vital role in enhancing preparedness, response, and recovery efforts, highlighting the multifaceted approach needed to mitigate the impact of future pandemics on health systems. Conclusions The identified strategies align with the attributes of a resilient healthcare system. By adopting these strategies, Ghana can build a resilient healthcare system that effectively addresses future challenges, guided by global insights and experiences.in F1000Research on 2024-10-10 14:38:04 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Use of the patient-centered outcome Days Alive and Out of Hospital in clinical studies on perioperative care: a scoping review protocol [version 1; peer review: awaiting peer review]
Background Various studies across different settings have validated Days Alive and Out of Hospital (DAOH) as a valuable outcome for clinical research in surgery and other fields. However, there is no clear consensus on the definitions and methods used to handle and report DAOH in perioperative care studies. Objective We aim to identify, describe, and summarize the available research on DAOH to understand how it is being conceptualized and utilized in clinical studies on perioperative care. Methods We will conduct a scoping review to analyze and synthesize the existing studies using DAOH to measure clinical results on perioperative care. We will search MEDLINE, Embase, Web of Science, ClinicalTrials.gov and CENTRAL. Screening, eligibility, inclusion and data extraction processes will be performed by two reviewers, with a third reviewer solving disagreements. We will present our results descriptively. Conclusions We expect to provide a comprehensive overview of how DAOH is conceptualized and utilized in clinical studies on perioperative care, with particular attention to methodological approaches and the role of electronic health-care records (EHRs) among the different regions.in F1000Research on 2024-10-10 14:17:35 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
EEG microstate transition cost correlates with task demands
by Giacomo Barzon, Ettore Ambrosini, Antonino Vallesi, Samir Suweis
The ability to solve complex tasks relies on the adaptive changes occurring in the spatio-temporal organization of brain activity under different conditions. Altered flexibility in these dynamics can lead to impaired cognitive performance, manifesting for instance as difficulties in attention regulation, distraction inhibition, and behavioral adaptation. Such impairments result in decreased efficiency and increased effort in accomplishing goal-directed tasks. Therefore, developing quantitative measures that can directly assess the effort involved in these transitions using neural data is of paramount importance. In this study, we propose a framework to associate cognitive effort during the performance of tasks with electroencephalography (EEG) activation patterns. The methodology relies on the identification of discrete dynamical states (EEG microstates) and optimal transport theory. To validate the effectiveness of this framework, we apply it to a dataset collected during a spatial version of the Stroop task, a cognitive test in which participants respond to one aspect of a stimulus while ignoring another, often conflicting, aspect. The Stroop task is a cognitive test where participants must respond to one aspect of a stimulus while ignoring another, often conflicting, aspect. Our findings reveal an increased cost linked to cognitive effort, thus confirming the framework’s effectiveness in capturing and quantifying cognitive transitions. By utilizing a fully data-driven method, this research opens up fresh perspectives for physiologically describing cognitive effort within the brain.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A diel multi-tissue genome-scale metabolic model of Vitis vinifera
by Marta Sampaio, Miguel Rocha, Oscar Dias
Vitis vinifera, also known as grapevine, is widely cultivated and commercialized, particularly to produce wine. As wine quality is directly linked to fruit quality, studying grapevine metabolism is important to understand the processes underlying grape composition. Genome-scale metabolic models (GSMMs) have been used for the study of plant metabolism and advances have been made, allowing the integration of omics datasets with GSMMs. On the other hand, Machine learning (ML) has been used to analyze and integrate omics data, and while the combination of ML with GSMMs has shown promising results, it is still scarcely used to study plants. Here, the first GSSM of V. vinifera was reconstructed and validated, comprising 7199 genes, 5399 reactions, and 5141 metabolites across 8 compartments. Tissue-specific models for the stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases. The potential of combining ML with GSMMs was explored by using ML to analyze the fluxomics data generated by green and mature grape GSMMs and provide insights regarding the metabolism of grapes at different developmental stages. Therefore, the models developed in this work are useful tools to explore different aspects of grapevine metabolism and understand the factors influencing grape quality.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
De novo sensorimotor learning through reuse of movement components
by George Gabriel, Faisal Mushtaq, J. Ryan Morehead
From tying one’s shoelaces to driving a car, complex skills involving the coordination of multiple muscles are common in everyday life; yet relatively little is known about how these skills are learned. Recent studies have shown that new sensorimotor skills involving re-mapping familiar body movements to unfamiliar outputs cannot be learned by adjusting pre-existing controllers, and that new task-specific controllers must instead be learned “de novo”. To date, however, few studies have investigated de novo learning in scenarios requiring continuous and coordinated control of relatively unpractised body movements. In this study, we used a myoelectric interface to investigate how a novel controller is learned when the task involves an unpractised combination of relatively untrained continuous muscle contractions. Over five sessions on five consecutive days, participants learned to trace a series of trajectories using a computer cursor controlled by the activation of two muscles. The timing of the generated cursor trajectory and its shape relative to the target improved for conditions trained with post-trial visual feedback. Improvements in timing transferred to all untrained conditions, but improvements in shape transferred less robustly to untrained conditions requiring the trained order of muscle activation. All muscle outputs in the final session could already be generated during the first session, suggesting that participants learned the new task by improving the selection of existing motor commands. These results suggest that the novel controllers acquired during de novo learning can, in some circumstances, be constructed from components of existing controllers.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Compression-based inference of network motif sets
by Alexis Bénichou, Jean-Baptiste Masson, Christian L. Vestergaard
Physical and functional constraints on biological networks lead to complex topological patterns across multiple scales in their organization. A particular type of higher-order network feature that has received considerable interest is network motifs, defined as statistically regular subgraphs. These may implement fundamental logical and computational circuits and are referred to as “building blocks of complex networks”. Their well-defined structures and small sizes also enable the testing of their functions in synthetic and natural biological experiments. Here, we develop a framework for motif mining based on lossless network compression using subgraph contractions. This provides an alternative definition of motif significance which allows us to compare different motifs and select the collectively most significant set of motifs as well as other prominent network features in terms of their combined compression of the network. Our approach inherently accounts for multiple testing and correlations between subgraphs and does not rely on a priori specification of an appropriate null model. It thus overcomes common problems in hypothesis testing-based motif analysis and guarantees robust statistical inference. We validate our methodology on numerical data and then apply it on synaptic-resolution biological neural networks, as a medium for comparative connectomics, by evaluating their respective compressibility and characterize their inferred circuit motifs.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Bayesian polynomial neural networks and polynomial neural ordinary differential equations
by Colby Fronk, Jaewoong Yun, Prashant Singh, Linda Petzold
Symbolic regression with polynomial neural networks and polynomial neural ordinary differential equations (ODEs) are two recent and powerful approaches for equation recovery of many science and engineering problems. However, these methods provide point estimates for the model parameters and are currently unable to accommodate noisy data. We address this challenge by developing and validating the following Bayesian inference methods: the Laplace approximation, Markov Chain Monte Carlo (MCMC) sampling methods, and variational inference. We have found the Laplace approximation to be the best method for this class of problems. Our work can be easily extended to the broader class of symbolic neural networks to which the polynomial neural network belongs.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Successful cardiac resynchronization therapy reduces negative septal work in patient-specific models of dyssynchronous heart failure
by Amanda Craine, Adarsh Krishnamurthy, Christopher T. Villongco, Kevin Vincent, David E. Krummen, Sanjiv M. Narayan, Roy C. P. Kerckhoffs, Jeffrey H. Omens, Francisco Contijoch, Andrew D. McCulloch
In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.in PLoS Computational Biology on 2024-10-10 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Structural Basis for Histaminergic Regulation of Neural Circuits in the Mouse Olfactory Bulb
Concluding Schema: Taken together with our previous reports, histaminergic neurons originating from the ventral tuberomammillary nucleus (VTM) project to the olfactory bulb (OB) without much branching prior to the OB. Their axons (orange lines) extended to the granule cell layer (GCL), the internal plexiform layer (IPL), the mitral cell layer (MCL), the external plexiform layer (EPL), the glomerular layer (GL), and the olfactory nerve layer (ONL) in the OB. The maximal density of histaminergic axions is observed in the GL, followed by the ONL and GCL. The glomerulus is enlarged to show a schematic diagram for synaptic transmission. The l-histidine decarboxylase–immunoreactive (HDC-ir) profiles received asymmetrical synapses (red arrows) from olfactory nerves (ON) and indicate synapses (green arrow) containing pleomorphic vesicles with postsynaptic densities to nonolfactory nerve elements (non-ON), thus forming serial synapses. It also receives asymmetric transmission (red arrow) from a profile that appears to be mitral/tufted (M/T) cell.
ABSTRACT
Odor information is modulated by centrifugal inputs from other brain regions to the olfactory bulb (OB). Neurons containing monoamines, such as serotonin, acetylcholine, and noradrenaline, are well known as centrifugal inputs; however, the role of histamine, which is also present in the OB, is not well understood. In this study, we examined the histaminergic neurons projecting from the hypothalamus to the OB. We used an antibody against histidine decarboxylase (HDC), a synthesizing enzyme of histamine, to identify histaminergic neurons and assess their localization within the OB and the ultrastructure of their fibers and synapses using multiple immunostaining laser microscopy, ultra-high voltage electron microscopy (EM), and EM to confirm their relationships with other neurons. To further identify the origin nucleus of the histaminergic neurons projecting to the OB, we injected the retrograde tracer FluoroGold and analyzed the pathway to the OB anterogradely. HDC-immunoreactive (-ir) fibers were abundant in the olfactory nerve (ON) layer compared to other monoamines. HDC-ir neurons received asymmetrical synapses from ONs and formed synapses containing pleomorphic vesicles with variable postsynaptic densities to non-ON elements, thus forming serial synapses. We also confirmed that histaminergic neurons project from the rostral ventral tuberomammillary nucleus to the granule cell layer of the OB and, for the first time, successfully visualized their axons from the hypothalamus to the OB. These findings indicate that histamine may regulate odor discrimination in the OB, suggesting a regulatory relationship between hypothalamic function and olfaction. We thus elucidate morphological mechanisms with tuberomammillary nucleus–derived histaminergic neurons involved in olfactory information.
in Journal of Comparative Neurology on 2024-10-10 10:55:08 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neurochemical Characterization of Dopaminoceptive Cells in Song Control Nuclei of Canaries and Their Activation During Song Production: A Multiplex Fluorescent In Situ Hybridization Study
Expression of dopamine receptors (Drd1, Drd2, Drd3—green) was quantified via RNAScope in HVC, Area X, and the periaqueductal gray (PAG) of testosterone treated canaries, along with colocalization of VGlut2 (orange), Gad2 (red), and Egr1 (pink). Illustrated are nuclei studied, dopaminergic projections of PAG, and an example HVC section.
ABSTRACT
Highly sensitive in situ hybridization procedures (RNAScope) were used to quantify the expression of three dopamine receptors (Drd1, Drd2, and Drd3) in two song control nuclei (HVC and the Area X of the basal ganglia) that are known to receive dopaminergic inputs and in the periaqueductal gray (PAG) of male and female canaries. Both sexes were treated with testosterone to ensure they would sing actively. We also determined the excitatory versus inhibitory phenotype of the cells expressing these receptors as well as their activation following a period of song production. The three receptor types were identified in each brain area, with the exception of Drd3 in Area X. The density of cells expressing each receptor varied as a function of receptor type and brain area. Surprisingly few sex differences were detected; they do not seem to explain the sex differences in testosterone-induced song. Overall, the density of Drd-positive cells was much lower in PAG than in the two song control nuclei. In HVC, the majority of cells expressing the three receptor subtypes were VGlut2-positive, whereas colocalization with Vglut2 occurred in few cells in Area X and in an intermediate proportion of cells in PAG. The number of inhibitory cells expressing dopamine receptors was limited. Most dopaminoceptive cells in Area X did not express either excitatory or inhibitory markers. Finally, cellular activation during singing behavior, as measured by the expression of Egr1, was observed in cells expressing each of the three dopamine receptor subtypes, except Drd3 in the PAG.
in Journal of Comparative Neurology on 2024-10-10 10:54:30 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Multiple Aneurysms and Cerebral Infarction in a Patient with Sneddon Syndrome
in Annals of Neurology on 2024-10-10 10:34:35 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Heightened Reticulospinal Excitability after Severe Corticospinal Damage in Chronic Stroke
Objective
After severe corticospinal tract damage poststroke in humans, some recovery of strength and movement proximally is evident. It is possible that alternate motor pathways, such as the reticulospinal tract, may be upregulated to compensate for the loss of corticospinal tract input. We investigated the extent of reticulospinal tract excitability modulation and its inter-dependence on the severity of corticospinal tract damage after stroke in humans.
Methods
We used a novel startle conditioned transcranial magnetic stimulation paradigm to elicit ipsilateral motor evoked potentials, an index of reticulospinal tract excitability, in 22 chronic stroke participants with mild to severe corticospinal tract damage and 14 neurotypical age-matched controls.
Results
We found that ipsilateral motor evoked potential presence was higher in the paretic arm of people with severe corticospinal tract damage compared to their non-paretic arm, people with mild corticospinal tract damage, and age-matched controls. Interestingly, ipsilateral motor evoked potential presence was correlated with motor impairment across the entire stroke cohort, whereby individuals with worse impairment exhibited more frequent ipsilateral motor evoked potentials (ie, higher reticulospinal tract excitability).
Interpretation
Following severe corticospinal tract damage, upregulated reticulospinal tract activity may compensate for a loss of corticospinal tract input, providing some proximal recovery of isolated and within-synergy movements, but deficits in performing out of synergy movements and finger fractionation remain. Interventions aimed at modulating the reticulospinal tract could be beneficial or detrimental to ameliorating motor impairment depending on the degree of reliance on this pathway for residual motor output. ANN NEUROL 2024
in Annals of Neurology on 2024-10-10 10:28:47 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Reply to “Letter on Multiple Acyl‐Coenzyme A Dehydrogenase Deficiency Is Associated with Sertraline Use”
in Annals of Neurology on 2024-10-10 10:28:07 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Role of Artificial intelligence model in prediction of low back pain using T2 weighted MRI of Lumbar spine [version 2; peer review: 1 approved, 1 approved with reservations]
Background Low back pain (LBP), the primary cause of disability, is the most common musculoskeletal disorder globally and the primary cause of disability. Magnetic resonance imaging (MRI) studies are inconclusive and less sensitive for identifying and classifying patients with LBP. Hence, this study aimed to investigate the role of artificial intelligence (AI) models in the prediction of LBP using T2 weighted MRI image of the lumbar spine. Methods This was a prospective case-control study. A total of 200 MRI patients (100 cases and controls each) referred for lumbar spine and whole spine screening were included. The scans were performed using 3.0 Tesla MRI (United Imaging Healthcare). T2 weighted images of the lumbar spine were segmented to extract radiomic features. Machine learning (ML) models, such as random forest, decision tree, logistic regression, K-nearest neighbors, adaboost, and deep learning methods (DL), such as ResNet and GoogleNet, were used, and performance measures were calculated. Results Our study showed that Random forest and AdaBoost are the most reliable ML models for predicting LBP. Random forest showed high performance with area under curve (AUC) values from 0.83 to 0.88 across all lumbar vertebrae and L2-L3, L3-L4, and L4-L5 intervertebral discs (IVDs), with AUCs of 0.88 the highest at L5-S1 IVD (0.92). Adaboost demonstrated high performance at the L2-L5 vertebrae with AUC values of 0.82 to 0.90, with the highest AUC (0.97) at the L5-S1 IVD. Among the DL models, GoogleNet outperformed the other models at 30 epochs with an accuracy of 0.85, followed by ResNet 18 (30 epochs) with an accuracy of 0.84. Conclusion The study demonstrated that ML and DL models can effectively predict LBP from MRI T2 weighted image of the lumbar spine. ML and DL models could also enhance the diagnostic accuracy of LBP, potentially leading to better patient management and outcomes.in F1000Research on 2024-10-10 10:17:52 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Bilaterally Symmetrical Globus Pallidus Infarction
in Annals of Neurology on 2024-10-10 10:04:11 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Re-conceptualization of the learning environment as a dynamic system [version 1; peer review: awaiting peer review]
In Japanese language education, the term "learning environment" is used in various contexts. This paper investigates the term "learning environment" in previous studies and notes that traditional learning environments have been characterized as "morphological characteristics learning environments" focusing on static learners. However, since learning environments involve a dynamic, reciprocal relationship where learners and their surroundings interact and evolve, the paper advocates for a re-conceptualization of "experiential-ecological learning environments" that captures this dynamic nature. Furthermore, to enrich the experiential-ecological learning environment for learners, the presence of learning environment engineers and the meaningful valuing of environmental enrichments is essential. Lastly, the paper emphasizes that by combining various individual learning experiences, it is possible to create a sustainable and richer learning environment.in F1000Research on 2024-10-10 07:54:40 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Why biodiversity matters in agriculture and food systems
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-10 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The third era of genomics is at risk of being dismantled across the global south
Science, Volume 386, Issue 6718, October 2024.
in Science on 2024-10-10 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The life of “ideas worth spreading”
Science, Volume 386, Issue 6718, Page 155-155, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Denizens of the dark
Science, Volume 386, Issue 6718, Page 154-154, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Direct optical measurement of intramolecular distances with angstrom precision
Science, Volume 386, Issue 6718, Page 180-187, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Evidence of a European seed dispersal crisis
Science, Volume 386, Issue 6718, Page 206-211, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Polar and quasicrystal vortex observed in twisted-bilayer molybdenum disulfide
Science, Volume 386, Issue 6718, Page 198-205, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Catalytic asymmetric fragmentation of cyclopropanes
Science, Volume 386, Issue 6718, Page 225-230, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Predicting pathogen mutual invasibility and co-circulation
Science, Volume 386, Issue 6718, Page 175-179, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Long-term stability in perovskite solar cells through atomic layer deposition of tin oxide
Science, Volume 386, Issue 6718, Page 187-192, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs
Science, Volume 386, Issue 6718, Page 167-175, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Unexpected westward range shifts in European forest plants link to nitrogen deposition
Science, Volume 386, Issue 6718, Page 193-198, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Science, Volume 386, Issue 6718, Page 217-224, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Ecological speciation in Darwin’s finches: Ghosts of finches future
Science, Volume 386, Issue 6718, Page 211-217, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The Poland experiment
Science, Volume 386, Issue 6718, Page 238-238, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
In Other Journals
Science, Volume 386, Issue 6718, Page 160-161, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Graphene, beyond lab benches
Science, Volume 386, Issue 6718, Page 144-146, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Tiny comets under the sea
Science, Volume 386, Issue 6718, Page 149-150, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Unwrapping stemness to revive T cells
Science, Volume 386, Issue 6718, Page 148-149, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Genomic patterns in the schizophrenia brain
Science, Volume 386, Issue 6718, Page 146-148, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Dangers of aging water infrastructure
Science, Volume 386, Issue 6718, Page 158-158, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Legal rhino horn trade: A thorny proposition
Science, Volume 386, Issue 6718, Page 157-158, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Protect white rhinos by legalizing horn trade
Science, Volume 386, Issue 6718, Page 157-157, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Coming of age
Science, Volume 386, Issue 6718, Page 138-143, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
News at a glance
Science, Volume 386, Issue 6718, Page 130-131, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
How racial bias can taint tenure decisions
Science, Volume 386, Issue 6718, Page 132-133, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Fermilab gets a not-quite-new boss to tackle its troubles
Science, Volume 386, Issue 6718, Page 133-134, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Duo honored for tiny RNAs key to development and disease
Science, Volume 386, Issue 6718, Page 134-134, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Physics award honors pioneers in artificial intelligence
Science, Volume 386, Issue 6718, Page 135-135, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Seed disperser declines threaten Europe’s plants
Science, Volume 386, Issue 6718, Page 136-136, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
El Niño fingered as likely culprit in record 2023 temperatures
Science, Volume 386, Issue 6718, Page 137-137, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Strong stuff
Science, Volume 386, Issue 6718, Page 143-143, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science in a shifting policy system
Science, Volume 386, Issue 6718, Page 125-125, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
New Products
Science, Volume 386, Issue 6718, Page 231-231, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Considerations for governing open foundation models
Science, Volume 386, Issue 6718, Page 151-153, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
In Science Journals
Science, Volume 386, Issue 6718, Page 159-161, October 2024.
in Science on 2024-10-10 05:59:01 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neural circuits for goal-directed navigation across species
Across species, navigation is crucial for finding both resources and shelter. In vertebrates, the hippocampus supports memory-guided goal-directed navigation, whereas in arthropods the central complex supports similar functions. A growing literature is revealing similarities and differences in the organization and function of these brain regions. We review current knowledge about how each structure supports goal-directed navigation by building internal representations of the position or orientation of an animal in space, and of the location or direction of potential goals. We describe input pathways to each structure – medial and lateral entorhinal cortex in vertebrates, and columnar and tangential neurons in insects – that primarily encode spatial and non-spatial information, respectively. Finally, we highlight similarities and differences in spatial encoding across clades and suggest experimental approaches to compare coding principles and behavioral capabilities across species. Such a comparative approach can provide new insights into the neural basis of spatial navigation and neural computation.in Trends in Neurosciences: In press on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Heightened lateral habenula activity during stress produces brainwide and behavioral substrates of susceptibility
Zhukovskaya et al. show that during social defeat, stress-susceptible mice have higher initial activity in LHb. Closed-loop LHb activation during defeat produces lasting behavioral and neural substrates of susceptibility. These results highlight the importance of activity levels in the LHb during the stress experience in determining stress outcomes.in Neuron: In press on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neuronal exosomes transport an miRISC cargo to preserve stem cell integrity during energy stress
Wong et al. show that the serotonergic neurons of C. elegans secrete exosomes at the onset of the dauer stage. These exosomes contain miRNAs that are preloaded onto Argonaute proteins, which translocate to the germline. After their internalization, the miRNAs silence germline mRNA targets to preserve germ cell integrity.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions
Chen et al. sorted diverse human antibody libraries against various multiple polyreactivity reagents, revealing that heavy-chain variable regions primarily mediate non-specificity. In addition, a machine learning model was developed to predict human antibody polyreactivity, revealing key features relevant to antibody recognition and drug design.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Visualizing the spatial organization of monocytes, interstitial macrophages, and tissue-specific macrophages in situ
Petit et al. show that the different mononuclear phagocyte subsets in non-lymphoid organs are spatially organized according to distinct sub-territories and depend on different molecular regulators. This spatial mapping provides a better understanding of the diversity of the mononuclear phagocyte system across different tissues.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Persistent bone marrow hemozoin accumulation confers a survival advantage against bacterial infection via cell-intrinsic Myd88 signaling
Zhu et al. report that hemozoin deposition in the bone marrow following Plasmodium infection induces a sustained myelopoiesis bias through a MyD88-dependent mechanism. This reprogramming results in monocytes producing increased reactive oxygen species, while the myelopoiesis bias enhances cytokine production, supporting emergency myelopoiesis and, ultimately, boosting antibacterial capacity.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients
Li et al. show that the absence of GPR40 enhances B cell activation, GC formation, and antibody production, exacerbating symptoms in a collagen-induced arthritis (CIA) model in mice. Mechanistically, GPR40 interacts with Gαq protein to regulate BCR signaling. GPR40 expression is reduced in B cells from patients with rheumatoid arthritis (RA), correlating with disease severity, highlighting GPR40 as a potential RA therapeutic target.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation
Hu et al. describe the upregulation of mitochondrial MOF in heart failure and report its disruptive activity in mitochondria respiration and cardiac function through the hyperacetylation of ATP5B. These findings underscore mtMOF’s critical role in cardiac energy metabolism and heart failure, highlighting the significance of enzyme-catalyzed acetylation in mitochondria.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Gut Bacteroides ovatus ameliorates renal fibrosis by promoting the production of HDCA through upregulation of Clostridium scindens
Si et al. describe that Bacteroides ovatus increases the production of hyodeoxycholic acid by upregulating Clostridium scindens. Hyodeoxycholic acid promotes the secretion of GLP-1, which activates the renal GLP-1 receptor, ameliorating chronic kidney disease. Neohesperidin, as a prebiotic, regulates the abundance of B. ovatus, contributing to the improvement of CKD.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
SRF promotes long-range chromatin loop formation and stem cell pluripotency
Tsaytler et al. discovered co-localization of the serum response factor (SRF) with CTCF and the cohesin subunit RAD21 at most of its binding sites. SRF depletion revealed a new role of SRF in TAD insulation and enhancer loop formation as well as the control of pluripotency factors in ESCs.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy
Osborne et al. use the 5xFAD mouse model to show that cerebral amyloid angiopathy impairs stroke recovery by disrupting the interaction between blood-brain barrier endothelial cells and hippocampal NPCs. Mechanistically, they demonstrate that reactivating the PI3K/CREB pathway stimulates adult neurogenesis, suggesting potential therapeutic strategies to enhance tissue recovery post stroke.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The flow of reward information through neuronal ensembles in the accumbens
Arroyo et al. show that NAcSh neuronal ensembles are distinct modules, each processing specific aspects of reward-guided behavior. These ensembles adapt during learning, forming different functional connections based on reward outcomes. The NAcSh network has a heavy-tailed distribution and central hubs that facilitate reward information flow.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Dopamine transients encode reward prediction errors independent of learning rates
Mah et al. find that rats use an uncertainty-based dynamic learning rate to adjust response vigor in a task with hidden states, which, they show, approximates normative Bayesian changepoint detection. However, despite strong behavioral effects, dopamine release in the nucleus accumbens does not reflect dynamic learning rates.in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation
(Cell Reports 43, 114180; May 28, 2024)in Cell Reports: Current Issue on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Being a PhD student in Morocco today
Early-career researchers in the Global South have to overcome obstacles that are not found in high-income countries, but in Morocco at least, the future is looking brighter than the past.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis
Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Astrogliosis and neuroinflammation underlie scoliosis upon cilia dysfunction
Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene. Here, we dissected the mechanisms of scoliosis onset in a zebrafish mutant for the rpgrip1l gene encoding a ciliary transition zone protein. rpgrip1l mutant fish developed scoliosis with near-total penetrance but asynchronous onset in juveniles. Taking advantage of this asynchrony, we found that curvature onset was preceded by ventricle dilations and was concomitant to the perturbation of Reissner fiber polymerization and to the loss of multiciliated tufts around the subcommissural organ. Rescue experiments showed that Rpgrip1l was exclusively required in foxj1a-expressing cells to prevent axis curvature. Genetic interactions investigations ruled out Urp1/2 levels as a main driver of scoliosis in rpgrip1 mutants. Transcriptomic and proteomic studies identified neuroinflammation associated with increased Annexin levels as a potential mechanism of scoliosis development in rpgrip1l juveniles. Investigating the cell types associated with annexin2 over-expression, we uncovered astrogliosis, arising in glial cells surrounding the diencephalic and rhombencephalic ventricles just before scoliosis onset and increasing with time in severity. Anti-inflammatory drug treatment reduced scoliosis penetrance and severity and this correlated with reduced astrogliosis and macrophage/microglia enrichment around the diencephalic ventricle. Mutation of the cep290 gene encoding another transition zone protein also associated astrogliosis with scoliosis. Thus, we propose astrogliosis induced by perturbed ventricular homeostasis and associated with immune cell activation as a novel pathogenic mechanism of zebrafish scoliosis caused by cilia dysfunction.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Sensory-memory interactions via modular structure explain errors in visual working memory
Errors in stimulus estimation reveal how stimulus representation changes during cognitive processes. Repulsive bias and minimum variance observed near cardinal axes are well-known error patterns typically associated with visual orientation perception. Recent experiments suggest that these errors continuously evolve during working memory, posing a challenge that neither static sensory models nor traditional memory models can address. Here, we demonstrate that these evolving errors, maintaining characteristic shapes, require network interaction between two distinct modules. Each module fulfills efficient sensory encoding and memory maintenance, which cannot be achieved simultaneously in a single-module network. The sensory module exhibits heterogeneous tuning with strong inhibitory modulation reflecting natural orientation statistics. While the memory module, operating alone, supports homogeneous representation via continuous attractor dynamics, the fully connected network forms discrete attractors with moderate drift speed and nonuniform diffusion processes. Together, our work underscores the significance of sensory-memory interaction in continuously shaping stimulus representation during working memory.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Topological stress triggers persistent DNA lesions in ribosomal DNA with ensuing formation of PML-nucleolar compartment
PML, a multifunctional protein, is crucial for forming PML-nuclear bodies involved in stress responses. Under specific conditions, PML associates with nucleolar caps formed after RNA polymerase I (RNAPI) inhibition, leading to PML-nucleolar associations (PNAs). This study investigates PNAs-inducing stimuli by exposing cells to various genotoxic stresses. We found that the most potent inducers of PNAs introduced topological stress and inhibited RNAPI. Doxorubicin, the most effective compound, induced double-strand breaks (DSBs) in the rDNA locus. PNAs co-localized with damaged rDNA, segregating it from active nucleoli. Cleaving the rDNA locus with I-PpoI confirmed rDNA damage as a genuine stimulus for PNAs. Inhibition of ATM, ATR kinases, and RAD51 reduced I-PpoI-induced PNAs, highlighting the importance of ATM/ATR-dependent nucleolar cap formation and homologous recombination (HR) in their triggering. I-PpoI-induced PNAs co-localized with rDNA DSBs positive for RPA32-pS33 but deficient in RAD51, indicating resected DNA unable to complete HR repair. Our findings suggest that PNAs form in response to persistent rDNA damage within the nucleolar cap, highlighting the interplay between PML/PNAs and rDNA alterations due to topological stress, RNAPI inhibition, and rDNA DSBs destined for HR. Cells with persistent PNAs undergo senescence, suggesting PNAs help avoid rDNA instability, with implications for tumorigenesis and aging.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Benchmarking reveals superiority of deep learning variant callers on bacterial nanopore sequence data
Variant calling is fundamental in bacterial genomics, underpinning the identification of disease transmission clusters, the construction of phylogenetic trees, and antimicrobial resistance detection. This study presents a comprehensive benchmarking of variant calling accuracy in bacterial genomes using Oxford Nanopore Technologies (ONT) sequencing data. We evaluated three ONT basecalling models and both simplex (single-strand) and duplex (dual-strand) read types across 14 diverse bacterial species. Our findings reveal that deep learning-based variant callers, particularly Clair3 and DeepVariant, significantly outperform traditional methods and even exceed the accuracy of Illumina sequencing, especially when applied to ONT’s super-high accuracy model. ONT’s superior performance is attributed to its ability to overcome Illumina’s errors, which often arise from difficulties in aligning reads in repetitive and variant-dense genomic regions. Moreover, the use of high-performing variant callers with ONT’s super-high accuracy data mitigates ONT’s traditional errors in homopolymers. We also investigated the impact of read depth on variant calling, demonstrating that 10× depth of ONT super-accuracy data can achieve precision and recall comparable to, or better than, full-depth Illumina sequencing. These results underscore the potential of ONT sequencing, combined with advanced variant calling algorithms, to replace traditional short-read sequencing methods in bacterial genomics, particularly in resource-limited settings.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor
The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells’ biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. In summary, our findings revealed resting NK cells exhibited a clinical relevance with CCLM, which may be exploited for novel strategies to improve therapeutic outcomes for patients with CCLM.in eLife on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Brain Sciences, Vol. 14, Pages 1014: Pre-Stimulus Activity of Left and Right TPJ in Linguistic Predictive Processing: A MEG Study
Brain Sciences, Vol. 14, Pages 1014: Pre-Stimulus Activity of Left and Right TPJ in Linguistic Predictive Processing: A MEG Study
Brain Sciences doi: 10.3390/brainsci14101014
Authors: Sara Lago Sara Zago Valentina Bambini Giorgio Arcara
Background. The left and right temporoparietal junctions (TPJs) are two brain areas involved in several brain networks, largely studied for their diverse roles, from attentional orientation to theory of mind and, recently, predictive processing. In predictive processing, one crucial concept is prior precision, that is, the reliability of the predictions of incoming stimuli. This has been linked with modulations of alpha power as measured with electrophysiological techniques, but TPJs have seldom been studied in this framework. Methods. The present article investigates, using magnetoencephalography, whether spontaneous oscillations in pre-stimulus alpha power in the left and right TPJs can modulate brain responses during a linguistic task that requires predictive processing in literal and non-literal sentences. Results. Overall, results show that pre-stimulus alpha power in the rTPJ was associated with post-stimulus responses only in the left superior temporal gyrus, while lTPJ pre-stimulus alpha power was associated with post-stimulus activity in Broca&rsquo;s area, left middle temporal gyrus, and left superior temporal gyrus. Conclusions. We conclude that both the right and left TPJs have a role in linguistic prediction, involving a network of core language regions, with differences across brain areas and linguistic conditions that can be parsimoniously explained in the context of predictive processing.
in Brain Sciences on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Brain Sciences, Vol. 14, Pages 1013: EEG Evidence of Acute Stress Enhancing Inhibition Control by Increasing Attention
Brain Sciences, Vol. 14, Pages 1013: EEG Evidence of Acute Stress Enhancing Inhibition Control by Increasing Attention
Brain Sciences doi: 10.3390/brainsci14101013
Authors: Bingxin Yan Yifan Wang Yuxuan Yang Di Wu Kewei Sun Wei Xiao
Objective: Research about the impact of acute stress on inhibitory control remains a contentious topic, with no consensus reached thus far. This study aims to investigate the effects of acute stress on an individual&rsquo;s inhibitory control abilities and to elucidate the underlying neural mechanisms by analyzing resting state electroencephalogram (EEG) data. Methods: We recruited 32 male college students through participant recruitment information to undergo within-subject experiments under stress and non-stress conditions. Physiological indicators (cortisol and heart rate), self-report questionnaires, and behavioral data from the Stroop task were collected before, during, and after the experiment. Additionally, a five-minute eyes closed resting state EEG data collection was conducted during the Stroop task before. Results: (1) Acute stress led to a reduction in the conflict effect during the participants&rsquo; Stroop task in individuals. (2) Stress resulted in an increase in the power of the beta in the resting state EEG. (3) Acute stress caused an increase in the duration of class D and an increase in the transition probabilities from classes C and B to class D in the microstates of the resting state EEG. (4) Acute stress leads to an increase in beta power values in individuals&rsquo; resting state EEGs, which is significantly negatively correlated with the reduction of the conflict effect in the Stroop task under stress. Conclusions: Acute stress can enhance individuals&rsquo; attentional level, thereby promoting inhibitory control performance.
in Brain Sciences on 2024-10-10 00:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
This Week in The Journal
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Neuritin Controls Axonal Branching in Serotonin Neurons: A Possible Mediator Involved in the Regulation of Depressive and Anxiety Behaviors via FGF Signaling
Abnormal neuronal morphological features, such as dendrite branching, axonal branching, and spine density, are thought to contribute to the symptoms of depression and anxiety. However, the role and molecular mechanisms of aberrant neuronal morphology in the regulation of mood disorders remain poorly characterized. Here, we show that neuritin, an activity-dependent protein, regulates the axonal morphology of serotonin neurons. Male neuritin knock-out (KO) mice harbored impaired axonal branches of serotonin neurons in the medial prefrontal cortex and basolateral region of the amygdala (BLA), and male neuritin KO mice exhibited depressive and anxiety-like behaviors. We also observed that the expression of neuritin was decreased by unpredictable chronic stress in the male mouse brain and that decreased expression of neuritin was associated with reduced axonal branching of serotonin neurons in the brain and with depressive and anxiety behaviors in mice. Furthermore, the stress-mediated impairments in axonal branching and depressive behaviors were reversed by the overexpression of neuritin in the BLA. The ability of neuritin to increase axonal branching in serotonin neurons involves fibroblast growth factor (FGF) signaling, and neuritin contributes to FGF-2-mediated axonal branching regulation in vitro. Finally, the oral administration of an FGF inhibitor reduced the axonal branching of serotonin neurons in the brain and caused depressive and anxiety behaviors in male mice. Our results support the involvement of neuritin in models of stress-induced depression and suggest that neuronal morphological plasticity may play a role in controlling animal behavior.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death
Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca2+-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca2+ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca2+ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca2+-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
{gamma}1 GABAA Receptors in Spinal Nociceptive Circuits
GABAergic neurons and GABAA receptors (GABAARs) are critical elements of almost all neuronal circuits. Most GABAARs of the CNS are heteropentameric ion channels composed of two α, two β, and one subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABAARs. Most GABAAR classifications rely on the heterogeneity of the α subunit (α1–α6) included in the receptor complex. Heterogeneity of the subunits (1–3), which mediate synaptic clustering of GABAARs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because 2 subunits greatly outnumber the other subunits in most brain regions. Here, we have investigated a potential role of non-2 GABAARs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides 2 subunits, 1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global 2 subunit deletion, which is lethal, spinal cord-specific loss of 2 subunits was well tolerated. GABAAR clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of 1 subunits that support the synaptic clustering of GABAARs in this site. They further suggest that 1 containing GABAARs contribute to the spinal control of nociceptive information flow.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Striatal Serotonin Release Signals Reward Value
Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have reward-related components. To date, research has focused on understanding these effects by measuring and manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior; however, they leave open many questions about the timing and location of serotonin's actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR activation-based sensor for serotonin (GRAB-5-HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without corelease confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
The Role of the Hippocampus in Consolidating Motor Learning during Wakefulness
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A Virtual In Vivo Dissection and Analysis of Socioaffective Symptoms Related to Cerebellum-Midbrain Reward Circuitry in Humans
Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared with other lobules. We discovered a mediolateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socioaffective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socioaffective regulation.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Symposium: What Does the Microbiome Tell Us about Prevention and Treatment of AD/ADRD?
Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Recent Visual Experience Reshapes V4 Neuronal Activity and Improves Perceptual Performance
Recent visual experience heavily influences our visual perception, but how neuronal activity is reshaped to alter and improve perceptual discrimination remains unknown. We recorded from populations of neurons in visual cortical area V4 while two male rhesus macaque monkeys performed a natural image change detection task under different experience conditions. We found that maximizing the recent experience with a particular image led to an improvement in the ability to detect a change in that image. This improvement was associated with decreased neural responses to the image, consistent with neuronal changes previously seen in studies of adaptation and expectation. We found that the magnitude of behavioral improvement was correlated with the magnitude of response suppression. Furthermore, this suppression of activity led to an increase in signal separation, providing evidence that a reduction in activity can improve stimulus encoding. Within populations of neurons, greater recent experience was associated with decreased trial-to-trial shared variability, indicating that a reduction in variability is a key means by which experience influences perception. Taken together, the results of our study contribute to an understanding of how recent visual experience can shape our perception and behavior through modulating activity patterns in the mid-level visual cortex.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Role of the STING->IRF3 Pathway in Ambient GABA Homeostasis and Cognitive Function
Targeting altered expression and/or activity of GABA (-aminobutyric acid) transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain, which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABAA inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon-independent manner. Stimulation of the STING->GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GAT expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A Systematic Structure-Function Characterization of a Human Mutation in Neurexin-3{alpha} Reveals an Extracellular Modulatory Sequence That Stabilizes Neuroligin-1 Binding to Enhance the Postsynaptic Properties of Excitatory Synapses
α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3αA687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cardiac-Sympathetic Contractility and Neural Alpha-Band Power: Cross-Modal Collaboration during Approach-Avoidance Conflict
As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence
During adolescence, cannabis experimentation is common, and its association with interindividual variations in brain maturation well studied. Cellular and molecular underpinnings of these system-level relationships are, however, unclear. We thus conducted a three-step study. First, we exposed adolescent male mice to -9-tetrahydrocannabinol (THC) or a synthetic cannabinoid WIN 55,212-2 (WIN) and assessed differentially expressed genes (DEGs), spine numbers, and dendritic complexity in their frontal cortex. Second, in human (male) adolescents, we examined group differences in cortical thickness in 34 brain regions, using magnetic resonance imaging, between those who experimented with cannabis before age 16 (n = 140) and those who did not (n = 327). Finally, we correlated spatially these group differences with gene expression of human homologs of mouse-identified DEGs. The spatial expression of 13 THC-related human homologs of DEGs correlated with cannabis-related variations in cortical thickness, and virtual histology revealed coexpression patterns of these 13 genes with cell-specific markers of astrocytes, microglia, and a type of pyramidal cells enriched in dendrite-regulating genes. Similarly, the spatial expression of 18 WIN-related human homologs of DEGs correlated with group differences in cortical thickness and showed coexpression patterns with the same three cell types. Gene ontology analysis indicated that 37 THC-related human homologs are enriched in neuron projection development, while 33 WIN-related homologs are enriched in processes associated with learning and memory. In mice, we observed spine loss and lower dendritic complexity in pyramidal cells of THC-exposed animals (vs controls). Experimentation with cannabis during adolescence may influence cortical thickness by impacting glutamatergic synapses and dendritic arborization.
in Journal of Neuroscience on 2024-10-09 16:30:20 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Signal Detection Theoretic Estimates of the Murine Absolute Visual Threshold Are Independent of Decision Bias
Decision bias influences estimates of the absolute visual threshold. However, most psychophysical estimates of the murine absolute visual threshold have not taken bias into account. Here we developed a one-alternative forced choice (1AFC) assay to assess the decision bias of mice at the absolute visual threshold via the theory of signal detection and compared our approach with the more conventional high-threshold theoretic approach. In the 1AFC assay, mice of both sexes were trained to signal whether they detected a flash stimulus. We directly measured both hit and false alarm rates, which were used to estimate d'. Using the theory of signal detection, we obtained absolute thresholds by interpolating the intensity where d' = 1 from d'-psychometric functions. This gave bias-independent estimates of the absolute visual threshold which ranged over sixfold, averaging ~1 R* in 1,000 rods (n = 7 mice). To obtain high-threshold theoretic estimates of the absolute visual threshold from the same mice, we estimated threshold intensities from the frequency of seeing curves, corrected for guessing. This gave us thresholds that were strongly correlated with decision bias, ranging over 13-fold and averaged ~1 R* in 2,500 rods. We conclude that the theory of signal detection uses false alarms to overcome decision bias and narrow the range of threshold estimates in mice, providing a powerful tool for understanding detection behavior near absolute visual threshold.
in eNeuro on 2024-10-09 16:30:14 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
A Novel Mouse Home Cage Lickometer System Reveals Sex- and Housing-Based Influences on Alcohol Drinking
Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress or novelty-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology.
in eNeuro on 2024-10-09 16:30:14 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 1 approved, 1 approved with reservations]
Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature.in F1000Research on 2024-10-09 15:15:33 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Economic factors influencing the empowerment of Peruvian women [version 1; peer review: awaiting peer review]
Objective To determine whether economic factors are crucial in empowering women, guiding them towards growth and development opportunities, achieving empowerment, and contributing to two sustainable development goals of the 2030 development agenda: ending poverty and achieving gender equality. Methodology The research was foundational, with a phenomenological and hermeneutic design. The applied technique was in-depth interviews with 12 women who had started a business within the last five years in a region of Peru. Results It is evident that economic factors are decisive in business experiences and decisions, highlighting the necessity of having contingency funds to prevent operational impacts. Through entrepreneurship, women achieved economic independence, enabling them to support their families and impacting their empowerment. It concludes that to promote economic opportunity equality, addressing financing needs, encouraging economic independence, strengthening family empowerment, improving customer management, and facilitating access to government funds are essential. Conclusions The narrative of the participants provides a solid foundation for designing specific policies and support programs that boost the economic empowerment of women entrepreneurs and encourage their active participation in the business sphere.in F1000Research on 2024-10-09 14:16:12 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Uncovering etiologic genes through whole exome sequencing in pediatric epilepsy: A case series from Thailand [version 1; peer review: awaiting peer review]
Introduction Developmental and epileptic encephalopathy (DEE) is characterized by seizures that are difficult to control for a long time and affect development in children who are previously normal or delayed. Therefore, children with DEE should be diagnosed promptly because certain types of the disease respond well to specific medications. In developing countries with limited universal coverage for whole exome sequencing (WES), identifying key clinical features in this patient group will help us make more accurate selections for investigations. The purpose of this study was to determine the prevalence of WES and its common clinical features in children with epileptic encephalopathy. Methods Ten volunteers aged 0-15 years were diagnosed with epilepsy with two or more symptoms of drug-resistant epilepsy, developmental delays, and abnormal nervous system/or dysmorphic features, and their electroencephalogram (EEG) showed abnormal background or specific patterns of epileptiform discharges. These were subjected to WES for the standard > 400 genes in the epilepsy panel. Results The established diagnosis was 4/10. Two known pathogenic variants, SCN2A and PCDH19. Two novel pathological variants, CHD2 and SCN1A. These are drug-resistant epilepsy, which is initially difficult to control and cannot stop antiseizure medications. Out of the 2/4 had moderate to severe intellectual disability. 3/4 had generalized epileptiform discharge activities. Conclusions This study showed a similar detection rate to that of a previous WES study. All the patients had difficult-to-treat epilepsy. For those who have not found abnormalities with the same clinical symptoms, further examinations using other methods should be conducted.in F1000Research on 2024-10-09 14:12:36 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Unifying approaches from statistical genetics and phylogenetics for mapping phenotypes in structured populations
by Joshua G. Schraiber, Michael D. Edge, Matt Pennell
In both statistical genetics and phylogenetics, a major goal is to identify correlations between genetic loci or other aspects of the phenotype or environment and a focal trait. In these 2 fields, there are sophisticated but disparate statistical traditions aimed at these tasks. The disconnect between their respective approaches is becoming untenable as questions in medicine, conservation biology, and evolutionary biology increasingly rely on integrating data from within and among species, and once-clear conceptual divisions are becoming increasingly blurred. To help bridge this divide, we lay out a general model describing the covariance between the genetic contributions to the quantitative phenotypes of different individuals. Taking this approach shows that standard models in both statistical genetics (e.g., genome-wide association studies; GWAS) and phylogenetic comparative biology (e.g., phylogenetic regression) can be interpreted as special cases of this more general quantitative-genetic model. The fact that these models share the same core architecture means that we can build a unified understanding of the strengths and limitations of different methods for controlling for genetic structure when testing for associations. We develop intuition for why and when spurious correlations may occur analytically and conduct population-genetic and phylogenetic simulations of quantitative traits. The structural similarity of problems in statistical genetics and phylogenetics enables us to take methodological advances from one field and apply them in the other. We demonstrate by showing how a standard GWAS technique—including both the genetic relatedness matrix (GRM) as well as its leading eigenvectors, corresponding to the principal components of the genotype matrix, in a regression model—can mitigate spurious correlations in phylogenetic analyses. As a case study, we re-examine an analysis testing for coevolution of expression levels between genes across a fungal phylogeny and show that including eigenvectors of the covariance matrix as covariates decreases the false positive rate while simultaneously increasing the true positive rate. More generally, this work provides a foundation for more integrative approaches for understanding the genetic architecture of phenotypes and how evolutionary processes shape it.in PLoS Biology on 2024-10-09 14:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Reply to “Comprehensive Analysis of Sex Differences in Amyotrophic Lateral Sclerosis Prognosis and Disease Progression”
in Annals of Neurology on 2024-10-09 09:48:28 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Relapse‐Associated and Relapse‐Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras
Objective
The introduction of disease-modifying therapies for multiple sclerosis (MS) has led to a deceleration of disease course over the years. Although decreased relapse rate constitutes a factor, the role of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) in MS course deceleration is still unclear.
Methods
We retrospectively examined long-term Expanded Disability Status Scale (EDSS) progression in patients referred to the MS Center of Montichiari (Italy) and diagnosed with relapsing–remitting MS from 1980 to 2022. To isolate PIRA, we deducted all EDSS changes associated with relapses from overall EDSS change. We compared the relative contribution of PIRA and RAW to EDSS progression in patients diagnosed in different periods using mixed-effects models.
Results
A total of 1,405 patients were included in the study, of whom 231 were diagnosed in 1980–1996 (pre-treatment era), 577 in 1997–2008 (injectable disease-modifying therapy era), and 597 after 2008 (oral drugs, monoclonal antibodies, and anti-CD20 era). Across ages, both PIRA and RAW were reduced in patients diagnosed in more recent periods as compared with earlier periods. The average contribution of PIRA to overall EDSS progression was already predominant in patients diagnosed in 1980–1996 (78%) and in 1997–2008 (76%), but it was significantly increased (p = 0.0009) in patients diagnosed in later years (87%).
Interpretation
The deceleration of MS course observed throughout the years is determined not only by fewer RAW events, but also by a reduction in PIRA. However, the shift toward a mostly relapse-independent progression highlights the importance of evaluating new therapies based on their effect on PIRA. ANN NEUROL 2024
in Annals of Neurology on 2024-10-09 09:38:55 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Computational Study Protocol: Leveraging Synthetic Data to Validate a Benchmark Study for Differential Abundance Tests for 16S Microbiome Sequencing Data [version 1; peer review: awaiting peer review]
Background The utility of synthetic data in benchmark studies depends on its ability to closely mimic real-world conditions and to reproduce results obtained from experimental data. Here, we evaluate the performance of differential abundance tests for 16S metagenomic data. Building on the benchmark study by Nearing et al. (1), who assessed 14 differential abundance tests using 38 experimental datasets in a case-control design, we validate their findings by generating synthetic datasets that mimics the experimental data. We will employ statistical tests to rigorously assess the similarity between synthetic and experimental data and to validate the conclusions on the performance of these tests drawn by Nearing et al. (1). This protocol adheres to the SPIRIT guidelines and is, to our knowledge, the first of its kind in computational benchmark studies. Methods We replicate Nearing et al.’s (1) methodology, incorporating synthetic data simulated using two distinct tools, mirroring each of the 38 experimental datasets. Equivalence tests will be conducted on 43 data characteristics comparing synthetic and experimental data, complemented by principal component analysis for overall similarity assessment. The 14 differential abundance tests will be applied to both synthetic and experimental datasets, evaluating the consistency of significant feature identification and the number of significant features per tool. Correlation analysis and multiple regression will explore how differences between synthetic and experimental data characteristics may affect the results. Conclusions Synthetic data enables the validation of findings through controlled experiments. We assess how well synthetic data replicates experimental data, validate previous findings and delineate the strengths and limitations of synthetic data in benchmark studies. Moreover, to our knowledge this is the first computational benchmark study to systematically incorporate synthetic data for validating differential abundance methods while strictly adhering to a pre-specified study protocol following SPIRIT guidelines, contributing significantly to transparency, reproducibility, and unbiased research.in F1000Research on 2024-10-09 09:21:47 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Epigallocatechin-3-gallate (EGCG) reduced expression of Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) in visceral pleural tissue cultures of patients with empyema [version 2; peer review: 1 approved
Abstract* Background Increased expression of signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) has been thought to influence the fibrosis process in many tissues. However, increased expression of these two factors has never been assessed in pleural fibrosis. Pleural fibrosis is a disease that usually results from various infectious processes, such as empyema. Fibrosis formation is recently known to be prevented by Epigallocatechin-3-gallate (EGCG), which is the most potent active substance found in Gambir (Uncaria gambir Roxb) leaves. Thus, further research is needed to determine the potential of EGCG to inhibit the process of pleural fibrosis caused by empyema. Methods An in vitro experimental study with post test-only controlled group was conducted on the pleural tissue of all patients who underwent decortication surgery due to empyema at Dr. M. Djamil Hospital, Padang, Indonesia between March 1st and April 30, 2024. Case samples were obtained by consecutive sampling, and three patients who met the inclusion criteria were obtained. Pleural tissue in each patient was then divided into several groups based on the treatment, namely the control group, 50 μg EGCG administration group, and 100 μg EGCG administration group. We used to determine SCUBE3 and TGF-β1 genes expression. Data were tested using ANOVA and Least Significant Difference (LSD) tests. Results There were significant differences in the SCUBE3 and TGF-β1 genes expression of 50 μg and 100 μg EGCG administration groups and the control groups in the 2 × 2 cm sample preparation (p=0.002) (p=0.014, respectively). Significant differences in TGF-β1 expression were also found between the groups treated with EGCG 50 μg and 100 μg and the control group in the 1 × 1 cm preparation (p=0.019). Conclusion EGCG can potentially decrease SCUBE3 and TGF-β1 expression in patients with pleural empyema.in F1000Research on 2024-10-09 09:14:33 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Mega corruptions in mega projects: Debating the dynamics of dam construction in Ethiopia [version 1; peer review: awaiting peer review]
Background This study critically examines the dynamics of corruption within Ethiopia’s dam construction projects, focusing on the Grand Ethiopian Renaissance Dam (GERD the Gilgel Gibe series, and Genale Dawa. The research highlights how weak management practices, insufficient oversight, and centralized decision-making, resulting in contribute to inflated costs, project delays, and compromised construction quality. A comprehensive understanding of these issues is crucial for addressing the challenges that impede Ethiopia’s infrastructure development. Methods A qualitative research approach was employed, integrating both primary and secondary data sources. The study utilized four theoretical frameworks—Principal-Agent Theory, Rent-Seeking Theory, Institutional Theory, and Neo-Patrimonialism—to analyze the structural and behavioral factors enabling corruption in Ethiopia’s dam construction projects. Results The study found that corruption is largely driven by weak management practices, insufficient oversight, and centralized decision-making. These factors contribute to inflated project costs, significant delays, and compromised construction quality. The lack of transparency and inadequate monitoring exacerbate these issues, leading to inefficient resource use and undermining the projects’ intended benefits. Economic impacts include increased public debt and strained financial resources. Socially, corruption erodes public trust and adversely affects the communities involved. The findings also highlight how information asymmetry and misaligned incentives contribute to corruption, with weak governance structures and informal networks further exacerbating the problem. These issues lead to cost overruns, increased debt, and diminished public confidence, which negatively impacts development outcomes. Conclusions While corruption in Ethiopia’s dam construction projects poses significant challenges, it is not insurmountable. Strengthening legal and regulatory frameworks, enhancing institutional capacity, promoting community participation, and leveraging international cooperation are crucial for mitigating these risks. Recommendations include implementing e-procurement systems, establishing independent oversight bodies, and promoting transparency to ensure these mega projects achieve their intended economic and social benefits.in F1000Research on 2024-10-09 08:54:56 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
China’s BRI in Central Asia & Its Impact: An Appraisal of the 10 Years [version 1; peer review: awaiting peer review]
The year 2023 marked the ten-year anniversary of Chinese President Xi Jinping inaugurating the ambitious Belt and Road Initiative (BRI) during his state visit to Kazakhstan. This article discusses China’s approach towards Central Asian countries under the BRI and their responses. While China has evidently profited from expanding connectivity along the ancient silk road and meeting its strategic interests, it is essential to understand whether Central Asian states have equally benefited from this initiative. Furthermore, the concern of debt-trap diplomacy has been prevalent in low-income countries where BRI has been operational. In this context, the article seeks to locate Central Asia in BRI, evaluating its impact on the region to determine if the BRI is a win-win for both the parties involved as touted by China. This article argues that despite differing interests and concerns about potential debt-traps, the BRI has been largely beneficial for both China and Central Asia given that BRI investments and projects remain crucial for the growth and development of these states and the region.in F1000Research on 2024-10-09 08:49:37 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 3; peer review: 3 approved with reserva
Background Aggregatibacter actinomycetemcomitans and Enterococcus faecalis are pathogenic bacteria of the oral cavity that cause various diseases such as periodontitis and endodontics. These bacteria are easily resistant to antibiotics. Photodynamic inactivation (PDI) is a method of inactivating microorganisms that utilizes light to activate a photosensitizer agent (PS) that produces reactive oxygen species causing cell lysis. Methods This study used the PDI method with a 405 nm diode laser at various energy density with the addition PS curcumin or chlorophyll Alfalfa, as much as 1.6 mg/ml on A. actinomycetemcomitans and E. faecalis bacteria. Results The study on E. faecalis bacteria showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of E. faecalis bacteria death 36.7% without PS, 69.30% with the addition of chlorophyll Medicago sativa L and 89.42% with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of bacterial death 35.81% without PS, 64.39% with the addition of chlorophyll Medicago sativa L and 89.82% with the addition of curcumin. PS was critical to the success of the PDI. Conclusions The addition of PS curcumin increased the effectiveness of reducing bacteria E. faecalis and A. actinomycetemcomitans compared to chlorophyll Medicago sativa L.in F1000Research on 2024-10-09 08:47:26 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Morphological and Autofluorescence Dataset for ‘Touch’ Epidermal Cell Populations Collected with Imaging Flow Cytometry [version 1; peer review: awaiting peer review]
Background New methods for processing ‘touch’ or trace biological samples is an ongoing priority for forensic caseworking laboratories. These samples often contain materials from multiple individuals in varying quantities and/or degrees of degradation. Rapid characterization of cellular material before DNA profiling can allow laboratories to screen samples for the presence of multiple contributors or the amount of biological material present. Methods This dataset contains autofluorescence and morphological profiles of epidermal cell populations analyzed using Imaging Flow Cytometry. The epidermal samples were aged for varying amounts of time prior to analysis. Multiple samples from the same individual were also collected to assess profile variations within and across the contributors. Conclusions This data set may be used to investigate variability in epidermal cell populations from different individuals and potential forensic signatures contained within the non-genetic components that comprise touch biological evidence.in F1000Research on 2024-10-09 08:46:23 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Cicada minimum age tree: Cryptic speciation and exponentially increasing base substitution rates in recent geologic time [version 4; peer review: 3 approved with reservations, 1 not approved]
We developed a new time-calibrated tree incorporating primarily endemic along with some cryptic Ryukyu islands cicada data, following the recent publication of global cicada data by Marshall et al. (2018), Łukasik et al. (2018), Simon et al. (2019), Price et al. (2019), and Hill et al. (2021). A total of 352 specimens were analyzed using BEAST v1. X software with a relaxed clock model. Fossil calibrations as old as Triassic were adopted largely following Johnson et al. (2018) and Moulds (2018), and a Quaternary geological event calibration was adopted following Osozawa et al. (2012, 2021b) and input into BEAST v1. X. Our timetree suggests that Tettigarctidae had a cicada basal lineage as old as 200.63 Ma, with Derotettiginae the next oldest lineage at 99.2 Ma. Tibicininae is a sister of the remaining subfamilies of Tettigomyiinae, Cicadettinae, and Cicadidae, and their species level differentiation and radiation began at 40.57 Ma. The Cicadinae clade consists of specific tribes with paraphyletic relationship, and the vicariance and adaptive radiation generated many cryptic species in each tribe. We estimated base substitution rate as a function of age, and the result strongly indicates an exponential increase of base substitution rate in recent geologic time. The consequent increase in cicada biodiversity, including generation of cryptic species in the Ryukyu Islands and surroundings, may have been driven by the generation and spreading of C4 grasses and coeval Quaternary climate change.in F1000Research on 2024-10-09 08:07:33 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-09 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
US federal resource allocations are inconsistent with concentrations of energy poverty
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-09 07:00:00 UTC.
-
- Wallabag.it! - Save to Instapaper - Save to Pocket -
Nearly linear orbital molecules on a pyrochlore lattice
Science Advances, Volume 10, Issue 41, October 2024.
in Science Advances on 2024-10-09 07:00:00 UTC.
Feed list
- Frontiers in Computational Neuroscience
- Frontiers in Ageing Neuroscience
- Frontiers in Neuroscience: Brain Imaging Methods
- Frontiers in Evolutionary Neuroscience
- Frontiers in Human Neuroscience
- Frontiers in Molecular Neuroscience
- Frontiers in Neuroscience: Neural Technology
- Frontiers in Neuroscience: Neurodegeneration
- Frontiers in Neurogenetics
- Frontiers in Neuroengineering
- Frontiers in Systems Neuroscience
- Frontiers in Synaptic Neuroscience
- Frontiers in Cellular Neuroscience
- Frontiers in Integrative Neuroscience
- Frontiers in Neural Circuits
- Frontiers in Neuroanatomy
- Frontiers in Neuroscience: Neurogenesis
- Frontiers in Neuroinformatics
- Trends in Neurosciences: In press
- Neuron: Current Issue
- Neuron: In press
- Cell Reports: Current Issue
- Cell Reports: In press
- PLoS Computational Biology
- PLoS Biology
- Nature
- Nature Neuroscience
- Nature Reviews
- Nature Photomics
- Nature Methods
- Nature Communications
- Nature Physics
- Nature scientific data
- Nature communications biology
- Annual Reviews of Neuroscience
- eLife
- Annals of Neurology
- Journal of Comparative Neurology
- Journal of Neuroscience Research
- Journal of Neuroscience
- BMC Neuroscience
- PNAS
- Neural Computation
- Network Neuroscience
- bioRxiv: Neuroscience
- arXiv: Quantitative Biology: Neurons and Cognition
- arXiv: Computer Science: Neural and Evolutionary Computing
- Current Opinion in Neurobiology
- Neural Networks
- Cerebral Cortex
- eNeuro
- Journal of Neurophysiology
- Science
- Science Advances
- Hippocampus
- ReScience C
- Physical Review E: Biological physics
- The Journal of Mathematical Neuroscience
- Behavioural and Brain Functions
- Brain Sciences
- F1000Research
- The Neuroscientist