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Sievert et al. visualize the dynamics of μS and μM PAS usage during plasmablast differentiation. Graded μS PAS usage occurs in cells that do or do not express Blimp-1; the latter function as cell intermediates of Blimp-1-expressing counterparts, which may have implications for derivatization of the secretory pathway.
in Cell Reports: Current Issue on 2025-02-08 00:00:00 UTC.
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Opioids can influence neuronal activity by regulating transmitter release. Here, Alexander and Bender demonstrate that delta opioid receptors engage different mechanisms to regulate release from parvalbumin- and somatostatin-expressing interneurons in mouse prefrontal circuits, resulting in differential temporal filtering of inhibitory transmission depending on presynaptic cell identity.
in Cell Reports: Current Issue on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56860-4
Enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains a challenge. Here, the authors report an iron-catalysed stereoselective NH imidation of sulfoxide, which is integrated with photocatalytic racemisation of sulfoxide, enabling a dynamic kinetic resolution strategy for direct and asymmetric synthesis of NH-sulfoximines.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56785-y
All genomes are replicated in a temporal order, though the determinants of such timing are poorly characterized. Here, the authors show that the unusual chromosome size-dependent DNA replication timing in Leishmania is influenced by RNA-DNA hybrids that are recognised by the endonuclease RNase H1.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56740-x
This study reveals that prion protein (PrP) promotes copper toxicity in Wilson disease by facilitating copper endocytosis. The authors demonstrate that suppressing PrP reduces copper overload and liver damage, offering a potential therapeutic strategy for this fatal inherited disorder.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56783-0
Single-cell replication timing (scRT) studies in cancer are challenging due to genomic heterogeneity. Here, the authors develop MnM, a machine learning tool that can provide heterogeneity-resolved scRT profiles, and apply it to a large single-cell dataset that includes tumours, cell lines, and patient-derived xenografts.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56107-2
Here, the authors show that genetic risk for hypertensive disorders of pregnancy increases cardiovascular risk, and present evidence suggesting that maintaining a healthy lifestyle and ideal metabolic status significantly reduces this risk.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56788-9
The automated synthesis of plasmonic nanoparticles with on-demand properties is a challenging task. Here the authors integrate a fluidic reactor, real-time characterization, and machine learning in a self-driven lab for the photochemical synthesis of nanoparticles with targeted properties.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56710-3
Textbook theory asserts that dislocation hardening inherently sacrifices ductility. Here, the authors report that high-density dislocations with segregation-modified configurations produced by additive manufacturing increase strength without compromising ductility.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Nature Communications, Published online: 08 February 2025; doi:10.1038/s41467-025-56743-8
Here, the authors use gnotobiotic mice to show that three core species of the human infant gut mycobiome (Rhodotorula mucilaginosa, Malassezia restricta and Candida albicans) exert distinct modulatory effects on the gut microbiome and immune landscape in white adipose tissue, with R. mucilaginosa and M. restricta increasing adiposity and exacerbating metabolic disease, while C. albicans resulted in leanness and resistance to diet-induced obesity.
in Nature Communications on 2025-02-08 00:00:00 UTC.
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Scientific Data, Published online: 08 February 2025; doi:10.1038/s41597-025-04577-w
Chromosome-level genome sequencing and assembly of the parasitoid wasp Leptopilina myrica
in Nature scientific data on 2025-02-08 00:00:00 UTC.
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Scientific Data, Published online: 08 February 2025; doi:10.1038/s41597-025-04558-z
An ontology-based rare disease common data model harmonising international registries, FHIR, and Phenopackets
in Nature scientific data on 2025-02-08 00:00:00 UTC.
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Communications Biology, Published online: 08 February 2025; doi:10.1038/s42003-025-07630-x
The study describes the development of FRET- and BRET-based receptor conformations sensors for the opioid receptor family. These sensors further revealed strongly agonist-dependent activation kinetics for the µ opioid receptor.
in Nature communications biology on 2025-02-08 00:00:00 UTC.
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Magnetic Resonance Imaging (MRI) offers many ways to non-invasively estimate the properties of white matter (WM) in the brain. In addition to the various metrics derived from diffusion-weighted MRI, one can estimate total WM volume from T1-weighted MRI, WM hyper-intensities from T2-weighted MRI, myelination from the T1:T2 ratio, or from the magnetisation-transfer ratio (MTR). Here we utilise the presence of all of these MR contrasts in a population based life-span cohort of 650 healthy adults [CamCAN cohort] to identify the latent factors underlying the covariance of 11 commonly-used WM metrics. Four factors were needed to explain 89% of the variance, which we interpreted in terms of 1) fibre density / myelination, 2) free-water / tissue damage, 3) fibre-crossing complexity and 4) microstructural complexity. These factors showed distinct effects of age and sex. To test the validity of these factors, we related them to measures of cardiovascular health and cognitive performance. Specifically, we ran path analyses 1) linking cardio-vascular measures to the WM factors, given the idea that WM health is related to cardiovascular health, and 2) linking the WM factors to cognitive measure, given the idea that WM health is important for cognition. Even after adjusting for age, we found that a vascular factor related to pulse pressure predicted the WM factor capturing free-water / tissue damage, and that several WM factors made unique predictions for fluid intelligence and processing speed. Our results show that there is both complementary and redundant information across common MR measures of WM, and their underlying latent factors may be useful for pinpointing the differential causes and contributions of white matter health in healthy aging.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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It will contribute to the development of sustainable artificial intelligence to elucidate the mechanism of neural modulation by which the brain of a living organism enable stable information processing in response to constantly changing external environments and internal states. As one of such cortical modulation, the present study focused on the effect of vagus nerve stimulation (VNS) therapy on information representation of the auditory cortex. By quantifying sound representation using machine learning, we investigated whether VNS alters cortical information representation in a layer-specific and frequency band-specific manner. A microelectrode array meticulously mapped the band-specific power and phase-locking value of sustained activities in every layer of the rat auditory cortex. Sparse logistic regression was used to decode the test frequency from these neural characteristics. The comparison of decoding accuracy before and after the application of VNS indicated that sound representation of the high-gamma band activity was impaired in the deeper layers, i.e., layers 5 and 6, while it was slightly improved in the superficial layers, i.e., layers 2, 3, and 4. Moreover, there was an improvement of sound representation in theta band activity in the deeper layers, demonstrating the layer-specific and frequency band-specific effect of VNS. Given that the cortical laminar structure and oscillatory activity in multiple frequency bands helps the auditory cortex to act as a hub for feed-forward and feed-back pathways in various information processing, the current findings support the possibility that VNS provide complex effects on brain function by altering the balance of cortical activity between layers and frequency bands.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Alzheimer disease (AD) has a complex etiology arising from largely unknown interactions between genetic and environmental factors. Even in populations with highly penetrant, disease-causing familial AD mutations, there is wide variation in disease onset and progression, suggesting that clinical symptoms are modified by genetics and environment. Identification of such modifiers is critical, as mechanisms that promote resilience to deleterious AD mutations, unhealthy diet, or aging represent promising therapeutic targets for AD and other causes of cognitive decline; global resilience factors that protect against multiple hits are among the highest priority for discovery. Both genetic and environmental protective factors in AD have been identified; however, interacting gene-environment (GxE) factors are incredibly difficult to study in human populations given complex genomes, poor self-reporting, data from underrepresented groups, and incompletely documented exposomes. Here, we used a population of mouse strains that model the polygenic nature of human AD to characterize individuals that display cognitive resilience to high-risk genetic and dietary perturbations to define and quantitate roles for genetics, sex, age, diet, and complex interactions that are nearly impossible to elucidate from humans or inbred AD mice. We found that some strains showed improved AD-related outcomes when fed a high-fat high-sugar (HFHS) diet, suggesting the need for personalized recommendations for dietary interventions in AD. Cognitive resilience is polygenetic; however, we found a locus on Chr 10 that was suggestively associated with cognitive resilience to AD in females, and this association was strengthened by HFHS diet, directly pointing to an interaction between specific genetic and environmental factors in AD risk and resilience. In conclusion, this study is the first of its kind to explore characteristics of resilience and GxE interactions in a genetically diverse mouse model. We present a subset of strains that exemplify global cognitive resilience to be leveraged for deep mechanistic studies aimed toward development of resilience-based and personalized therapeutic interventions.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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AMPA-type glutamate receptors (AMPARs) underlie most of the excitatory synaptic transmission in the brain and are crucial for implementing long-term synaptic plasticity. AMPARs are multi-protein complexes composed of two types of subunits: pore-forming subunits GluA1-4 that assemble in the endoplasmic reticulum and form the glutamate-gated ion channel, and auxiliary subunits that modulate receptor biophysical properties and mediate their forward trafficking to the plasma membrane. Here, using a combination of theoretical and experimental approaches, we elucidate the kinetics of essential trafficking steps and the protein sources necessary to explain the experimentally observed distribution of AMPARs and the response of different AMPAR subtypes to LTP induction. Our data indicate that the mRNA coding for one of the most abundant AMPAR auxiliary subunits, CNIH-2, is abundant in dendrites. Consistent with this mRNA distribution, CNIH-2 is locally synthesized. In contrast, the pore-forming subunits GluA1 and GluA2 are mostly synthesized in the cell body. CNIH-2 synthesis increases after the (chemical) induction of long-term potentiation. Strikingly, the translation of CNIH-2 is required for the plasma membrane insertion of GluA2-containing receptors and not GluA1-homomeric AMPARs. Using the selective trafficking of GluA2-containing AMPARs by CNIH-2, our computational model can explain the distinct temporal profiles in response to plasticity induction of two major subtypes of AMPARs, the slow-response of the calcium impermeable (GluA2-containing) and fast kinetics of the calcium-permeable (GluA2-lacking) AMPARs.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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A primary goal of systems neuroscience is to discover how ensembles of neurons transform inputs into goal-directed behavior, a process known as neural computation. A powerful framework for understanding neural computation uses neural dynamics - the rules that describe the temporal evolution of neural activity - to explain how goal-directed input-output transformations occur. As dynamical rules are not directly observable, we need computational models that can infer neural dynamics from recorded neural activity. We typically validate such models using synthetic datasets with known ground-truth dynamics, but unfortunately existing synthetic datasets don not reflect fundamental features of neural computation and are thus poor proxies for neural systems. Further, the field lacks validated metrics for quantifying the accuracy of the dynamics inferred by models. The Computation-through-Dynamics Benchmark (CtDB) fills these critical gaps by providing: 1) synthetic datasets that reflect computational properties of biological neural circuits, 2) interpretable metrics for quantifying model performance, and 3) a standardized pipeline for training and evaluating models with or without known external inputs. In this manuscript, we demonstrate how CtDB can help guide the development, tuning, and troubleshooting of neural dynamics models. In summary, CtDB provides a critical platform for model developers to better understand and characterize neural computation through the lens of dynamics.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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The natively unfolded tau protein is extremely soluble, which poses challenges when modeling neurofibrillary tangle (NFT) pathology in Alzheimers disease (AD). To overcome this hurdle, we combined P301L and S320F mutations (PL-SF) to generate a rapid and reliable platform to expedite the discovery of factors that modulate tau aggregation. Using this model, we evaluated heat-shock proteins (Hsp), traditionally linked to tau pathology, but whose role in AD remains enigmatic and controversial. In primary neurons, expression of Hsp70, but not Hsc70 or Hsp90, exacerbated tau aggregation. Conversely, lowering of Hsp70 by shRNA or a chaperone-deficient tau mutant (PL-SF-4delta) reduced tau phosphorylation and abrogated tau aggregation, highlighting Hsp70 as a key driver of tau aggregation. Functionally, mature aggregate-bearing neurons showed deficits in neuronal firing and network communication, while chaperone-binding deficient tau variants displayed reduced tau pathology and restored network properties. This study provides a powerful cell intrinsic model for accelerated tau aggregation, which can be harnessed to identify regulators of tau aggregation as promising therapeutic targets.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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The ability of animals to interact with their environment hinges on the brain's capacity to distinguish between patterns of sensory information and accurately attribute them to specific sensory organs. The mechanisms by which neuronal circuits discriminate and encode the source of sensory signals remain elusive. To address this, we utilized as a model the posterior lateral line system of larval zebrafish, which is used to detect water currents. This system comprises a series of mechanosensory organs called neuromasts, which are innervated by neurons from the posterior lateral line ganglion. By combining single-neuromast optogenetic stimulation with whole-brain calcium imaging, we developed a novel approach to investigate how inputs from neuromasts are processed. Upon stimulating individual neuromasts, we observed that neurons in the brain of the zebrafish show diverse selectivity properties despite a lack of topographic organization in second-order circuits. We further demonstrated that complex combinations of neuromast stimulation are represented by sparse ensembles of neurons within the medial octavolateralis nucleus (MON) and found that neuromast input can be integrated nonlinearly. Our approach offers an innovative method for spatiotemporally interrogating the zebrafish lateral line system and presents a valuable model for studying whole-brain sensory encoding.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Targeting specific cell types is essential for understanding their functional roles in the brain. Although genetic approaches enable cell-type-specific targeting in animals, their application to higher mammalian species, such as nonhuman primates, remains challenging. Here, we developed a nontransgenic method using bridge proteins to direct viral vectors to cells endogenously expressing -opioid receptors (MORs), a G protein-coupled receptor. The bridge protein comprises the avian viral receptor TVB, the MOR ligand {beta}-endorphin ({beta}ed), and an interdomain linker. EnvB-enveloped viruses bind to the TVB component, followed by the interaction of {beta}ed with MORs, triggering viral infection in MOR-expressing cells. We optimized the secretion signals, domain configurations, and interdomain linkers of the bridge proteins to maximize viral targeting efficiency and specificity. Alternative configurations incorporating different ligands and viral receptors also induced viral infection in MOR-expressing cells. The optimized {beta}ed-f2-TVB bridge protein with EnvB-pseudotyped lentiviruses induced infection in MOR-expressing cells in the striatum of mice and monkeys. An intersectional approach combining {beta}ed-f2-TVB with a neuron-specific promoter refined cell-type specificity. This study establishes the foundation for the rational bridge protein design and the feasibility of targeting G protein-coupled receptors beyond tyrosine kinase receptors, thereby expanding targetable cell types in the brain and throughout the body.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain oscillations, and in relation to subjective experience. We find that DMT shifts the dynamics of brain oscillations away from criticality in alpha and adjacent frequency bands. In this context, entropy is increased while complexity is reduced. We find that the criticality shifts observed in alpha and theta bands correlate with the intensity ratings of ego-dissolution, a hallmark of psychedelic experience. Finally, using a recently developed metric, the functional excitatory-inhibitory ratio, we find that the DMT-induced criticality shift in brain oscillations is towards subcritical regimes. These findings have major implications for the understanding of psychedelic mechanisms of action in the human brain and for the neurological basis of altered states of consciousness.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Cortical implants are a proven clinical neurotechnology with the potential to transform our understanding of cognitive processes. These processes rely on complex neuronal networks that are difficult to selectively probe or stimulate. Optogenetics offers cell-type specificity, but achieving the density and coverage required for chronic, high-resolution modulation remains a challenge. Here we present a 100-element LED array (200 m pixel pitch, 2 x 2 mm2 footprint) coupled into a miniaturised, flexible system suitable for chronic implantation and optogenetic stimulation of the surface of the mouse cortex. The LEDs can remain stable for over 300 hours continuous operation time in-vivo, allowing for months-long chronic experiments. Simultaneous electrophysiology recordings confirmed robust neuronal responses corresponding to low LED drive currents (<5 mA), minimising thermal effects and supporting future wireless operation. The spatial resolution of neuronal responses was consistent with a simulated model of light scattering in the cortical layers, enabling device optimisation. Behavioural experiments with chronically implanted mice demonstrated robust learning during discrimination tasks using spatially distinct optogenetic stimulation patterns.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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When does compulsive-like drug seeking emerge? Despite decades of research, and critical advances in our understanding of brain processes leading to addiction, this question remains widely unanswered. So far, behavioral models assessing compulsive-like cocaine seeking following an extended access to cocaine failed to capture the development of its compulsive seeking. In fact, compulsive-like animals immediately displayed pathological seeking when facing its negative consequences of drug seeking, usually materialized by an unescapable mild electric shock on the paws. Here, we designed a new task, "Punished Seeking during Extended access" (PSE), by inserting punished seeking trials within the sessions of extended access to cocaine. We show that compulsive-like cocaine seeking progressively emerges after several PSE sessions, once cocaine intake has been escalated. We thus provide the addiction community a pertinent model to explore brain mechanisms sustaining the emergence of compulsive-like cocaine seeking.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Although migraine attacks are considered to arise in the brain, the exact mechanisms by which the brain can generate migraine pain remain unclear. Visual cortex hyperexcitability has been observed consistently across different migraine subtypes. During cortical hyperexcitability events, aberrant neurotransmitter release drives heightened G-coupled receptor signaling in cortical astrocytes, which in turn release gliotransmitters and other factors with algesic properties. This study investigated whether heightened activation of cortical astrocytes Gq-coupled signaling is sufficient to drive peripheral meningeal nociceptive responses linked to the generation of migraine headaches. Using a rat model, we employed an AAV-based chemogenetic approach that allows selective activation of visual cortex astrocyte Gq-GPCR signaling. We combined this chemogenetic approach with in vivo single-unit recording of trigeminal meningeal nociceptors to assess changes in their ongoing activity and mechanosensitivity. We further used behavioral testing of migraine-like behaviors and pharmacological targeting of calcitonin gene-related peptide (CGRP), using a monoclonal antibody (anti-CGRP mAb) to further assess the relevance of cortical astrocyte activation to migraine. We discovered that heightened activation of Gq-coupled signaling in visual cortex astrocytes drives persistent discharge and increased mechanosensitivity of trigeminal nociceptors innervating the meninges overlying the visual cortex. Cortical astrocytic activation also generated cephalic mechanical pain hypersensitivity, reduced exploratory behavior, and anxiety-like behaviors linked to migraine headaches. Targeting calcitonin gene-related peptide signaling, implicated in migraine pathophysiology, using a monoclonal antibody effectively suppressed astrocyte-mediated meningeal nociceptor discharge and alleviated migraine-related behaviors. Our findings reveal a previously unappreciated role for augmented visual cortex astrocyte signaling as a triggering factor sufficient to generate meningeal nociception and migraine pain and greatly expand our understanding of migraine pathophysiology.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Previous studies on animal models suggested that visual areas involved in motion processing could undergo important cortical reorganizations following retinal damages. This could have major implications for patients suffering from macular degeneration (MD), the leading cause of vision loss in older adults. Here, we performed fMRI recordings in a group of maculopathy patients (including individuals suffering from age-related macular degeneration or from Stargardt's Disease) and a control group to characterize the motion processing cortical network in MD patients and determine whether this network undergoes significant large-scale reorganisations following the onset of the scotoma. We used an experimental protocol based on random-dot kinematograms (RDKs) classically employed to characterize motion-selective areas in the brain. To ensure that the visual information processed by the two groups was equivalent, the visual field in each control participant was masked using an artificial scotoma directly derived from clinical measurements in their paired patient. We found that in MD patients, translational motion elicited significant and robust activations in a restricted cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6 and a portion of primary visual areas (V1, V2 and V3) connected to peripheral vision. Importantly, the same patterns of responses were also observed in control participants. Moreover, the extent and strength of activation within these motion-selective areas did not differ significantly between the two groups. Altogether, these results suggest that in humans, the motion-selective network does not undergo significant large-scale cortical reorganizations following the onset of MD.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Circadian behaviors need to be properly phased with the day/night cycle to be beneficial. We previously showed that the microRNA miR-124 regulates circadian behavior phase in Drosophila. Here, we report that miR-124 expression during larval development is required for proper phasing of both morning and evening peaks of activity in adults. Loss of miR-124 results in significant miswiring within the circadian neural network and severely alters neural activity rhythms in the ventral Lateral Neurons (s-LNvs) and the posterior Dorsal Neurons 1 (DN1ps), which control the timing of morning and evening activity. Silencing the s-LNvs in miR-124 mutant flies restores the phase of evening activity, while activating the DN1ps rescues the phases of both morning and evening activities. Our findings thus reveal the pivotal role of miR-124 in sculpting the circadian neural network during development and its long-lasting impact on circuit activity and adult circadian behavior.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Rationale: Xylazine, a sedative typically used in veterinary medicine, has been increasingly detected as an adulterant in the unregulated opioid supply and present in opioid overdose deaths. Therefore, xylazine-adulterated fentanyl is a growing public health concern. People who use drugs have reported that xylazine changes and prolongs the effects of fentanyl. Objectives: We used standard operant drug discrimination procedures to better understand how xylazine impacts the discriminative stimulus/interoceptive effects of fentanyl. Methods: Male and female Long-Evans rats (n=23) were trained to discriminate fentanyl (0.032 mg/kg intraperitoneal) such that one lever was reinforced with sucrose on days when fentanyl was administered, and the other lever was reinforced when vehicle was administered. Once rats met testing criteria, we tested a dose range of fentanyl to confirm discriminative stimulus control, then we tested if xylazine alone produced fentanyl-like effects and if the addition of xylazine to fentanyl impacted fentanyl interoceptive effects. Results: Stimulus control was confirmed, as rats showed increased percent responses on the fentanyl-appropriate lever as well as decreased response rates for increasing doses of fentanyl. Xylazine alone did not substitute for the stimulus effects of fentanyl but produced similar response rate reductions as fentanyl alone. Xylazine co-administered with fentanyl potentiated the stimulus effects of lower doses of fentanyl in both males and females and potentiated response rate reductions. Conclusions: These results indicate that xylazine enhances the interoceptive effects of fentanyl, which may inform clinical research about xylazine-adulterated fentanyl.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Huntington's disease (HD) is a devastating movement disorder without a current cure. Although the monogenic basis of HD is well-defined, the complex downstream effects that underlie behavioral symptoms are poorly understood. These effects include cortical dysfunctions, yet the role of specific cortical neuronal subtypes in HD symptoms remain largely unexplored. Here, we used longitudinal in vivo two-photon calcium imaging to examine the activity of two cortical inhibitory neuron (IN) subtypes and excitatory corticostriatal projection neurons (CSPNs) in the motor cortex of R6/2 HD mouse model throughout disease progression. We found that motor deficits in R6/2 mice were accompanied by neuron type-specific abnormalities in movement-related activity, including hypoactivity of vasoactive intestinal peptide (VIP)-INs and CSPNs. Optogenetic activation of VIP-INs in R6/2 mice restored healthy levels of activity in VIP-INs and their downstream CSPNs and ameliorated motor deficits in R6/2 mice. Our findings highlight cortical INs as a potential therapeutic target for HD and possibly other neurological diseases.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Synaptic connections between neurons determine the flow of information in the brain. Changes in synaptic weight, along with synapse formation and pruning, reshape the functional connectivity of neural circuits - key mechanisms underlying learning and memory. However, the relationship between functional strength and the structural dynamics of individual glutamatergic synapses in the living mammalian brain remains poorly understood. Specifically, how spine morphology and stability relate to functional adaptations is unclear. Here, we repeatedly recorded excitatory postsynaptic calcium transients in single postsynaptic spines of CA1 neurons in response to optogenetic stimulation of presynaptic CA3 cells in awake, head-fixed mice for over 2 weeks. We found that functional connectivity predicted both the structural stability and clustering of synaptic inputs. Spines with large responses exhibited larger volume and higher stability compared to non-responding spines. Over time, responses were highly variable at individual synapses, but stable at the dendritic level, suggesting that dendritic branches receive stable input despite large fluctuations at individual synapses.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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A critical phase of mammalian brain development takes place after birth. Neurons of the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during the first postnatal month, while properties of immature neurons, such as the capacity for robust axon outgrowth, are lost. The genetic and epigenetic programs controlling prenatal development are well studied, but our understanding of the transcriptional mechanisms that regulate postnatal neuronal maturation is comparatively lacking. By integrating chromatin accessibility and gene expression data from two subtypes of neocortical pyramidal neurons in the neonatal and maturing brain, we predicted a role for the Kruppel-Like Factor (KLF) family of Transcription Factors in the developmental regulation of neonatally expressed genes. Using a multiplexed CRISPR Interference (CRISPRi) knockdown strategy, we found that a shift in expression from KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) during early postnatal development functions as a transcriptional switch to first activate, then repress a set of shared targets with cytoskeletal functions including Tubb2b and Dpysl3. We demonstrate that this switch is buffered by redundancy between KLF paralogs, which our multiplexed CRISPRi strategy is equipped to overcome and study. Our results indicate that competition between activators and repressors within the KLF family regulates a conserved component of the postnatal maturation program that may underlie the loss of intrinsic axon growth in maturing neurons. This could facilitate the transition from axon growth to synaptic refinement required to stabilize mature circuits.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Tauopathies are neurodegenerative diseases that are pathologically characterized by accumulation of misfolded microtubule-associated protein tau aggregates in the brain. Deubiquitination, particularly by OTULIN, a unique deubiquitinase targeting methionine-1 (M1) linkages from linear ubiquitin chain assembly complex (LUBAC)), is reportedly associated with the accumulation of neurotoxic proteins in several neurodegenerative diseases, likely including tauopathies. To investigate the potential roles of OTULIN in tauopathies, we analyzed the OTULIN interactome in hippocampal tissues from PS19 transgenic (Tg) mice and their non-transgenic (nTg) littermate controls using affinity purification-mass spectrometry (AP-MS). We identified 705 and 800 proteins enriched in Tg and nTg samples, respectively, with a protein false discovery rate (FDR) of <1%. Of these, 189 and 205 proteins were classified as probable OTULIN interactors in Tg and nTg groups, respectively, based on Significance Analysis of INTeractome (SAINT) score of [≥]0.80 and FDR of [≤] 5%. A total of 84 proteins were identified as OTULIN interactors in the PS19 Tg group, while 100 proteins were associated with OTULIN in the nTg controls. Functional enrichment analyses revealed that OTULIN-interacting proteins in the nTg group were enriched in pathways related to spliceosome, complement and coagulation cascades, and ribosome, whereas those in the Tg group were associated with immune response and autophagy. These findings suggest that OTULIN-interacting proteins may play a critical role in the pathogenesis of tauopathy in this mouse model.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Neurons maintain their morphology over prolonged periods of adult life with limited regeneration after injury. C. elegans DIP-2 is a conserved regulator of lipid metabolism that affects axon maintenance and regeneration after injury. Here, we investigated genetic interactions of dip-2 with mutants in genes involved in lipid biosynthesis and identified roles of phospholipids in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in the de novo phospholipid synthesis (Kennedy) pathway. Loss of function mutants of cept-2 or ept-1 show reduced axon regrowth and failure to maintain axon morphology. We demonstrate that CEPT-2 is cell-autonomously required to prevent age-related axonal defects. Interestingly, loss of function in dip-2 led to suppression of the axon regrowth phenotype observed in either cept-2 or ept-2 mutants, suggesting that DIP-2 acts to counterbalance phospholipid synthesis. Our findings reveal the genetic regulation of lipid metabolism to be critical for axon maintenance under injury and during aging.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Perceptual alternation in human binocular rivalry is more likely to occur during certain respiratory phases. In this paper, we show that the respiration dependence of perceptual alternations can be reproduced by a randomly connected recurrent neural network coupled with respiration relevant information via a neuromodulator of norepinephrine (NA). We considered two models of NA modulations; NA increases or decreases the nonlinearity of the activation function of neurons, and we found that the shape of the likelihood function of perceptual alternation depends only on respiratory phase, regardless of whether NA increases or decreases neural nonlinearity. Our results suggest that periodic neuromodulation facilitates the switching of competing neural states in specific phases and that this effect is independent of the excitatory or inhibitory effect of NA.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Mounting evidence suggests that transcranial alternating current stimulation (tACS) can enhance response inhibition, a cognitive process crucial for sustained effort and decision-making. However, most prior studies have focused on within-session effects, with limited investigation into the effects of repeated applications, which are crucial for clinical applications. We examined the effects of repeated bifocal tACS targeting the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA), regions implicated in response inhibition, on inhibitory control. We also explored changes to functional connectivity and whether this stimulation improved simulated driving performance. Thirty young adults (18-35 years) were assigned to either a sham or tACS group (20 Hz, 20 minutes), undergoing five stimulation sessions over two weeks. Resting-state electroencephalography (EEG) was used to assess functional connectivity between the preSMA and rIFG during the first and fifth bifocal tACS sessions and at a 7-day follow-up. Response inhibition was measured using a stop signal task (SST) administered throughout the sessions. Participants completed two simulated driving tasks (braking, general driving) before the first and after the final tACS intervention. Results revealed a significant improvement in functional connectivity in the tACS group across sessions, although no changes were observed in response inhibition and the braking task. Notably, general driving performance improved, with participants demonstrating closer adherence to the speed limit and greater spare attentional capacity. These findings highlight the potential of repeated bifocal tACS to enhance functional connectivity and related cognitive and motor processes, suggesting promising clinical applications for addressing issues related to cortical connectivity.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Alpha synuclein (aSyn) is an abundant protein that, in the brain, is concentrated in neuronal presynaptic boutons and associates with synaptic vesicles. aSyn is strongly linked with Parkinson's disease (PD) due to its accumulation in pathognomonic inclusions in neuronal cells, including in glutamatergic neurons. While increased expression of wild-type (WT) aSyn due to multiplications of the SNCA gene, or the expression of mutant forms of aSyn, can cause familial forms of PD, it is still unclear whether increased levels of aSyn alone are sufficient to impair synaptic function. Previous studies have used experimental systems that do not allow systematic characterisation of presynaptic physiology. To address this gap in research, we used lentiviral vectors to overexpress human aSyn (haSyn) in continental and autaptic glutamatergic neurons from rodent hippocampus and systematically analysed their presynaptic function. Virally-transduced neurons exhibited levels of expression of haSyn that mimic those associated with triplications of the SNCA gene in PD patients (2-fold increase in total aSyn), as determined using quantitative immunofluorescence imaging and immunoblots. Neuronal toxicity, neuronal morphology, and SNAP-25, a presynaptic protein, were not altered in continental cultures. Finally, a systematic characterization of autaptic neurons expressing haSyn exhibited no significant difference in any parameter of synaptic function, including basal properties of evoked and spontaneous neurotransmitter release, and synaptic plasticity compared to neurons infected with a control virus. These results indicate that rodent glutamatergic neurons are resilient to aSyn overexpression. In conclusion, our findings suggest neurotoxicity associated with aSyn overexpression is not universal, and that a deeper understanding of aSyn biology and pathobiology is necessary.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Two subtypes of serotonin (5-HT) within the serotonin 2 class, the 5-HT2C receptor and the 5-HT2A receptor, are involved in the regulation of spinal motor function. The 5-HT2C receptor has been implicated in various aspects of volitional movement, such as locomotion, gait, coordination, and muscle contraction, as well as in involuntary motor behavior like spasms, which affect many individuals with spinal cord injury. Despite their known involvement in motor function, little is known about their physiological roles and the changes that occur after spinal cord injury. In this study, we have investigated the volitional and involuntary motor behavior of male and female uninjured and spinal cord injured knock-out mice that lack the functional 5-HT2C receptor by comparing these genetically manipulated mice to typical-functioning sex-matched wildtype mice. Behavioral assessments revealed differences in volitional muscle strength and coordination, as well as hyperreflexia, between the groups observed. Additionally, ex vivo sacral cord preparation data suggest that 5-HT2C receptor knock-out mice exhibit less spasm-like activity than wildtype mice, corroborating our results from behavioral testing in which the flexor withdrawal reflex of the hindlimbs was assessed. To investigate potential compensatory changes in 5-HT2C receptor and 5-HT2A receptor expression following spinal cord injury, western blot analysis was performed on lumbar and sacral spinal cord tissue from wildtype and 5-HT2C receptor knock-out mice before and after injury. Sex, genotype, and injury status significantly influenced 5-HT2C receptor and 5-HT2A receptor relative expression and distribution of these receptors in both spinal cord regions. Through a comprehensive approach combining behavioral assessments, electrophysiological experiments, and whole-tissue protein analysis, our findings provide strong evidence that the 5-HT2C receptor plays a critical role in both volitional motor function and involuntary motor behavior. Additionally, we identified significant differences in the regional distribution and relative expression of the 5-HT2C receptor and 5-HT2A receptor based on sex, genotype, and injury status.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Rab4 GTPase, essential for endosomal sorting and trafficking, is implicated in synaptic atrophy and dementia. To uncover the underlying mechanism, we studied the correlation between Rab4 vesicle transport in axons and episodic remodeling of synapses in the central nervous system (CNS) of Drosophila larvae. We found that synapse-bound traffic and presynaptic enrichment of Rab4 vesicles increase during the programmed, transient contraction of synapses in the ventral neuropil region at a specific larval stage. This coincides with the episodic activation of insulin and Vps34-mediated signaling, which elevates phosphatidylinositol-3-phosphate levels on Rab4 vesicles. The presence of this phospholipid on Rab4-associated vesicles recruit a PX-domain-containing motor protein, Klp98A, accelerating synapse-directed traffic. This, in turn, increases presynaptic enrichment of Rab4 during the developmentally programmed synapse contraction phase. Our findings elucidate the molecular mechanism that regulates developmental synaptic plasticity in the CNS via insulin signaling and directed axonal transport of endosomes.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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The "Other-Race Effect" (ORE) refers to the enhanced memory individuals have for faces within their own racial group compared to other races. This effect is attributed to limited exposure to different races and social-motivational factors affecting face processing. While past research has explored this effect through neuroimaging methods, the precise neural mechanisms that underlie the ORE remain a subject of ongoing investigation. Previous studies have largely adopted a modular perspective, concentrating on the differential activation of face-processing regions when comparing same-race and other-race facial recognition behaviors. However, given the multifaceted nature of the ORE, an exclusive focus on specialized regions may miss the pivotal role played by non-face-preferential brain areas in modulating this phenomenon. In the present study, we take a broader data-driven perspective using graph-theoretical techniques to investigate whole-brain network disparities in same- and other-race facial recognition. Our findings reveal a substantial impact of race on functional connectivity during face memorization. While other-race face recognition benefitted from higher local efficiency during encoding, reduced local efficiency was advantageous for memorization of same-race faces. Notably, successful other-race recognition was disproportionately supported by locally efficient processing in regions among the ventral and dorsal attention networks.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Interleukin-6 dysregulation has been implicated in the pathological progression of Alzheimer's disease (AD), a leading cause of dementia in the ageing population. Here we show that chronic neuroinflammation elicited by transgenic expression of IL-6 and systemic IL-6 deficiency influences the phenotype of the Tg2576 mouse model of AD, modulating mortality, body weight, behavioral and cognitive traits, amyloidosis, and neuroinflammation. While the conventional understanding of AD pathophysiology emphasizes the central role of Amyloid beta; peptides and amyloid plaques in the development and progression the disease, the absence of amyloidosis in the brain in a specific subset of Tg2576 mice challenges this notion. This suggests that several Tg2576-related traits may manifest independently of Amyloid beta, pointing to a potential contribution of alternative APP-related factors or pathways to the phenotypic alterations observed in Tg2576 mice. Together, our findings underscore the complexity of AD pathogenesis and emphasize the multifaceted nature of IL-6 in both physiological and neurodegenerative processes, particularly in the context of AD.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Local connectivity analyses in fMRI such as the Vogt-Bailey Index, investigate the prevalence of co-fluctuations in the time-series of adjacent voxels. While there have been in silico assessments of the VB Index, this technique has not yet been assessed in vivo. This study has two aims: first, to assess the VB Index using a task paradigm with well established a priori expectations on the brain region predominantly responsible for executing this task to determine whether the VB Index highlights this area. Second, we investigate if, and how, the spatial resolution of the sequence protocols employed, with their inherent effects on the signal-to-noise ratio, affect the resultant VB maps. A cohort of 10 research volunteers underwent fMRI acquisitions utilising a block design finger tapping experiment. Each volunteer was scanned with three sequence protocols, with all parameters equivalent except for the volume of the voxels. The resulting parametric maps derived using the VB Index were compared with those obtained from the conventional General Linear Model approach. Particular emphasis was placed on the identification of the hand portion of the motor homunculus. Across sequence protocols, the VB Index consistently identified elevated local connectivity in, qualitatively, the same portion of the motor cortex as that yielded by the General Linear Model based on the task paradigm. However, the VB Index also detected elevated local connectivity outside the motor cortex while the General Linear Model results were mostly restricted to the motor cortex. The consistently high VB Index, across sequence protocols, in the cortical region associated with an fMRI task paradigm, despite the approach's agnosticism to that task, provides support for the biological relevance of such local connectivity measures.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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The small GTPase CDC42 promotes axon growth through actin filament polymerization and this growth is driven by axonal localization of the mRNA encoding the prenylated CDC42 isoform (Prenyl-Cdc42). Here, we show that axonal Prenyl-Cdc42 mRNA transport and translation are decreased by growth-inhibiting stimulation and increased by growth-promoting stimulation. In contrast, axonal RhoA mRNA transport and translation are increased by growth inhibition but unaffected by growth promotion. Localized increase in KHSRP in response to growth inhibitory stimulation, through elevation of intracellular Ca2+, promotes decay of axonal Prenyl-Cdc42 mRNA. Distinct 3'UTR motifs regulate transport and stability of axonal Prenyl-Cdc42 mRNA. KHSRP protein binds to a Prenyl-Cdc42 mRNA motif within nt 801-875 and the mRNA is remarkably increased in axons of Khsrp-/- mice. Selective depletion of Prenyl-Cdc42 mRNA from axons reverses the accelerated axon regeneration seen in Khsrp-/- mice.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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To compute motor plans or intentions, the nervous system must translate target locations into body-centered coordinates. Visual stimuli, however, are sensed in retinotopic coordinates, which shift with eye movements. Furthermore, sensorimotor delays necessitate predictive processing. How does the brain compute timely gaze-invariant target locations? The dorsal visual pathway encodes spatial intentions, yet the underlying dynamic mechanisms remain elusive. Using multilevel analysis, we characterized intention coding in area V6A of the Posterior Parietal Cortex during delayed reaching tasks under diverse gaze-target conditions. We revealed a consistent population-level intention coding in V6A as eye positions changed. Next, we identified differential single-cell encoding of gaze and reaching targets in retinotopic, gaze-posture, and body-centered coordinates and elucidated the dynamical spatial normalization. Finally, we demonstrated context-dependent predictive spatial encoding in V6A, advancing our understanding of the temporal evolution of predictive visuomotor transformations during motor planning.
in bioRxiv: Neuroscience on 2025-02-08 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 168: The Application of Entropy in Motor Imagery Paradigms of Brain–Computer Interfaces
Brain Sciences doi: 10.3390/brainsci15020168
Authors:
Chengzhen Wu
Bo Yao
Xin Zhang
Ting Li
Jinhai Wang
Jiangbo Pu
Background: In motor imagery brain&ndash;computer interface (MI-BCI) research, electroencephalogram (EEG) signals are complex and nonlinear. This complexity and nonlinearity render signal processing and classification challenging when employing traditional linear methods. Information entropy, with its intrinsic nonlinear characteristics, effectively captures the dynamic behavior of EEG signals, thereby addressing the limitations of traditional methods in capturing linear features. However, the multitude of entropy types leads to unclear application scenarios, with a lack of systematic descriptions. Methods: This study conducted a review of 63 high-quality research articles focused on the application of entropy in MI-BCI, published between 2019 and 2023. It summarizes the names, functions, and application scopes of 13 commonly used entropy measures. Results: The findings indicate that sample entropy (16.3%), Shannon entropy (13%), fuzzy entropy (12%), permutation entropy (9.8%), and approximate entropy (7.6%) are the most frequently utilized entropy features in MI-BCI. The majority of studies employ a single entropy feature (79.7%), with dual entropy (9.4%) and triple entropy (4.7%) being the most prevalent combinations in multiple entropy applications. The incorporation of entropy features can significantly enhance pattern classification accuracy (by 8&ndash;10%). Most studies (67%) utilize public datasets for classification verification, while a minority design and conduct experiments (28%), and only 5% combine both methods. Conclusions: Future research should delve into the effects of various entropy features on specific problems to clarify their application scenarios. As research methodologies continue to evolve and advance, entropy features are poised to play a significant role in a wide array of fields and contexts.
in Brain Sciences on 2025-02-08 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 167: Gut–Brain Axis and Brain Microbiome Interactions from a Medical Perspective
Brain Sciences doi: 10.3390/brainsci15020167
Authors:
Borros Arneth
Background: The gut microbiome directly impacts brain health and activity, meaning the two are closely associated. This relationship suggests a link between microbial imbalances and diseases such as Alzheimer&rsquo;s, although multiple other contributing factors, such as genetics, also play a part. Additionally, recent studies discovered that cerebrospinal fluid has some microbial deoxyribonucleic acid (DNA), which can be interpreted to mean a microbiome exists in the brain too. The vagus nerve and the central nervous and immune systems are responsible for the connection between the brain and gut microbiome. Aims and Objectives: The main aim of this systematic review is to analyze existing research on the gut&ndash;brain axis and the brain microbiome to fill the current knowledge gap. Materials and Methods: A search was conducted on the PubMed database based on a set of predefined MeSH terms. Results: After the search, 2716 articles meeting the MeSH parameters were found in PubMed. This list was then downloaded and analyzed according to the inclusion/exclusion criteria, and 63 relevant papers were selected. Discussion: Bacteria in the gut microbiome produce some substances that are considered neuroactive. These compounds can directly or indirectly affect brain function through the gut&ndash;brain axis. However, various knowledge gaps on the mechanisms involved in this connection need to be addressed first.
in Brain Sciences on 2025-02-08 00:00:00 UTC.
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Background Chronic non-specific neck pain is one of the most prevalent musculoskeletal disorders affecting work and lifestyle. Physiotherapy techniques, such as stretching and strength training, have beneficial effects on neck pain. Telerehabilitation exercise programmes could readily address the growing concern of patient adherence to home-based exercise programmes, while being time- and cost-effective. This study aimed to determine the effectiveness of telerehabilitation exercise intervention in females with chronic non-specific neck pain by measuring the pain score, disability index, cervical range of motion (CROM), cervical muscle endurance, and patient adherence. Methods In this pilot randomized controlled trial, 31 females (mean age 22.7 ± 2.1 years) were given a 6-week home-based exercise programme based on their assigned group: telerehabilitation (TR) – online software or conventional (CG) – exercise manual. Baseline measurements were collected using the Visual Analog Scale for Pain (VAS Pain), Neck Disability Index (NDI) questionnaire, CROM using the CROM instrument, and cervical muscle endurance through the Craniocervical Flexion Test (CCFT), and repeated after six weeks, in addition to adherence. SPSS version 26.0 was used for all statistical analyses. Results Based on mixed model ANOVA measures (0 week and 6 weeks), within-group comparisons for both groups showed statistical significance in favour of the exercise programme, for all variables (p<0.05). Telerehabilitation group showed significantly more increase in cervical rotation ROM R (0.006) and L (0.03) post-exercise programme, and longer duration of treatment session (0.02) as compared to conventional group. Between-group comparisons showed no significant differences for all other variables. Conclusions Based on our findings, both groups showed significant improvement in neck pain, disability, cervical ROM, and cervical muscle endurance; however, no group was found superior to the other in this regard. While both groups showed good adherence to the frequency of sessions, telerehabilitation exhibited better adherence to the duration of the exercise sessions.
in F1000Research on 2025-02-07 16:54:40 UTC.
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Ongoing digitalization and data-driven developments in materials science and engineering (MSE) emphasize the growing importance of reusing research data and enabling machine accessibility, which requires robust data management and consistent semantic data representation. Ontologies have emerged as powerful tools for establishing interoperable and reusable data structures from inconsistent data structures. Despite advancements in semantic data representation for specific applications, integrating application ontologies with primary data repositories, such as electronic lab notebooks (ELNs), to feed world data remains an open task. As a use case in the MSE domain, this work presents a system based on semantic technologies from the point of view of engineers, developed with the help of information scientists, and unraveled on a small scale. The development of an application ontology (AO) was elaborated for flame spray pyrolysis (FSP) processes with the implementation of a data pipeline. The proposed FSP application ontology emerges from experimental in-house best-practice procedures and is adapted to the mid-level Project Material Digital core ontology (PMDco) to allow interoperability within the MSE domain. The pipeline retrieves manually acquired experimental data from an ELN, translates it into a machine-actionable format, and converts it into a Resource Description Framework (RDF) format to support semantic interoperability. The latter was stored in a triple store with a SPARQL interface, enabling findable and accessible datasets that are searchable and traceable. By creating semantically linked data structures in line with FAIR principles, this approach allows traceable and findable experimental results between stakeholders through both human-readable and machine-actionable formats. Seamless integration of the modular microservices of the data pipeline within established lab practices minimizes disruption while maintaining the software framework. The present work demonstrates the practical implementation of a FAIR data pipeline within a laboratory setting, paving the way for future data-centric science.
in F1000Research on 2025-02-07 16:52:49 UTC.
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Background Although observational studies demonstrate that higher levels of vascular risk factors are associated with an increased risk of dementia, these associations might be explained by confounding or other biases. Mendelian randomization (MR) uses genetic instruments to test causal relationships in observational data. We sought to determine if genetically predicted modifiable risk factors (type 2 diabetes mellitus, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, and circulating glucose) are associated with dementia by meta-analysing published MR studies. Secondary objectives were to identify heterogeneity in effect estimates across primary MR studies and to compare meta-analysis results with observational studies. Methods MR studies were identified by systematic search of Web of Science, OVID and Scopus. We selected primary MR studies investigating the modifiable risk factors of interest. Only one study from each cohort per risk factor was included. A quality assessment tool was developed to primarily assess the three assumptions of MR for each MR study. Data were extracted on study characteristics, exposure and outcome, effect estimates per unit increase, and measures of variation. Effect estimates were pooled to generate an overall estimate, I2 and Cochrane Q values using fixed-effect model. Results We screened 5211 studies and included 12 primary MR studies after applying inclusion and exclusion criteria. Higher genetically predicted body mass index was associated with a higher odds of dementia (OR 1.03 [1.01, 1.05] per 5 kg/m2 increase, one study, p=0.00285). Fewer hypothesized vascular risk factors were supported by estimates from MR studies than estimates from meta-analyses of observational studies. Conclusion Genetically predicted body mass index was associated with an increase in risk of dementia.
in F1000Research on 2025-02-07 16:50:35 UTC.
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Background The aim of this study was to observe and analyze vascular function in ‘prolonged sitting’, followed by a yoga asana routine and pranayama intervention. Participants in this study include those who work from desks in offices. The study required the participants to attend on three separate days at random, and they had to finish a computerized test on each day. On the first day, participants were required to complete a computer test while sitting still for four hours (with the exception of washroom breaks). The next day, they underwent a computerized test along with a pranayama intervention. Finally, on the last day, they underwent a computerized test along with a yoga asana intervention. At the start of the study and after two and four hours, we measured the diameter and velocity of the common carotid artery (CCA) and superficial femoral artery (SFA). Methods The study was a within-subjects prospective single-center trial conducted in the Department of Radio-Diagnosis and Imaging, Kasturba Medical Hospital, Manipal, India, between September 2022 and January 2023. Participants were asked to do one of the following ‘activities’ over successive weeks: Week 1 – Prolonged sitting; Week 2 – Pranayama intervention; and Week 3 – Yoga asana intervention during prolonged sitting. The baseline and follow-up variables of pulse velocity, endothelial thickness, and shear rate were assessed for normality through a Shapiro-Wilk Test. Results Our sample included 11 participants with moderate physical activity, five with high physical activity and one with low physical activity. Yoga asana intervention comprised participants sitting continuously for four hours, with a yoga asana intervention being provided every hour, lasting for 10 minutes. Conclusions Yoga asana improves vascular functions in prolonged sitting conditions. This routine can promote the concept of interrupted sitting and ways to reduce it with efficient yoga asana practice without changing the work culture and provide better physical relief. Trial registration Clinical Trials Registry – India ( CTRI/2022/09/045628), date of registration: 19/09/2022(CTRI/2022/9/045628)https://ctri.nic.in/Clinicaltrials/main1.php?EncHid=16349.27799,
in F1000Research on 2025-02-07 16:48:19 UTC.
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by Brinkley Raynor Bellotti, Elvis W. Díaz, Micaela De la Puente-León, Maria T. Rieders, Sergio E. Recuenco, Michael Z. Levy, Ricardo Castillo-Neyra
Background From smallpox to poliomyelitis, halting contagion transmission through simultaneous mass vaccination is ubiquitous and often perceived as the only possible solution. But implementing mass vaccination campaigns in large populations within a short period poses many challenges. For example, in Arequipa, Peru, sweeping mass vaccination campaigns conducted yearly over a single weekend have failed to achieve the required ‘herd immunity’ to halt canine rabies transmission. Contrary to the global paradigm of a simultaneous campaign, the 2022 Arequipa rabies campaign was implemented at the sub-district level (patches), with dates of the campaign staggered across 6 months.
Methods We constructed a stochastic, metapopulation model to examine how the timing of pulsed vaccination campaigns across patches can affect metapopulation dynamics. We explore general metapopulation dynamics for pulsed vaccinations as well as parameterizing the model for canine rabies in Arequipa, Peru. We simulated how the timing of the planned vaccination campaign, staggered over 6 months versus a single yearly pulse, affected the prospects for regional rabies elimination.
Results Metapopulation dynamics can affect the efficacy of pulsed vaccination campaigns. In the case of Arequipa, Peru, the planned staggered mass dog vaccination campaign has the potential for local elimination with the tradeoffs of increased time to elimination and increased outbreak size due to metapopulation dynamics.
Conclusions Heterogeneities caused by control strategies enactment at sub-population scales should be accounted for when modeling transmission dynamics. In Arequipa, Peru, although metapopulation dynamics may allow for re-introduction of canine rabies in previously vaccinated patches when mass dog vaccination campaigns are staggered temporally over 6 months, continuous mass vaccination reaching recommended vaccination coverage levels is sufficient to eliminate canine rabies.
in PLoS Computational Biology on 2025-02-07 14:00:00 UTC.
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by Eliezyer Fermino de Oliveira, Pranjal Garg, Jens Hjerling-Leffler, Renata Batista-Brito, Lucas Sjulson
High-dimensional data have become ubiquitous in the biological sciences, and it is often desirable to compare two datasets collected under different experimental conditions to extract low-dimensional patterns enriched in one condition. However, traditional dimensionality reduction techniques cannot accomplish this because they operate on only one dataset. Contrastive principal component analysis (cPCA) has been proposed to address this problem, but it has seen little adoption because it requires tuning a hyperparameter resulting in multiple solutions, with no way of knowing which is correct. Moreover, cPCA uses foreground and background conditions that are treated differently, making it ill-suited to compare two experimental conditions symmetrically. Here we describe the development of generalized contrastive PCA (gcPCA), a flexible hyperparameter-free approach that solves these problems. We first provide analyses explaining why cPCA requires a hyperparameter and how gcPCA avoids this requirement. We then describe an open-source gcPCA toolbox containing Python and MATLAB implementations of several variants of gcPCA tailored for different scenarios. Finally, we demonstrate the utility of gcPCA in analyzing diverse high-dimensional biological data, revealing unsupervised detection of hippocampal replay in neurophysiological recordings and heterogeneity of type II diabetes in single-cell RNA sequencing data. As a fast, robust, and easy-to-use comparison method, gcPCA provides a valuable resource facilitating the analysis of diverse high-dimensional datasets to gain new insights into complex biological phenomena.
in PLoS Computational Biology on 2025-02-07 14:00:00 UTC.
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by Richard J. Wang, Yadira Peña-García, Muthuswamy Raveendran, R. Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D. Yoder, Joe H. Simmons, Jeffrey Rogers, Matthew W. Hahn
Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality—without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to the pattern found across mammals, we find a much larger effect of maternal age than paternal age on mutation rates in the aye-aye. In addition, older aye-aye mothers transmit substantially more mutations than older fathers. We carry out both computational and experimental validation of our results, contrasting them with results from baboons and other primates using the same methodologies. Further, we analyze a set of DNA repair and replication genes to identify candidate mutations that may be responsible for the change in mutation bias observed in aye-ayes. Our results demonstrate that mutation bias is not an immutable trait, but rather one that can evolve between closely related species. Further work on aye-ayes (and possibly other lemuriform primates) should help to explain the molecular basis for sex-biased mutation.
in PLoS Biology on 2025-02-07 14:00:00 UTC.
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by Ivan Jarić, Pavel Pipek, Ana Novoa
Common altmetrics indices are limited and biased in the social media that they cover. In this Perspective, we highlight how and why altmetrics should broaden its scope to provide more reliable metrics for scientific content and communication.
Common altmetrics indices are limited and biased in the social media that they cover. This Perspective highlights how and why altmetrics should broaden its scope to provide more reliable metrics for scientific content and communication.
in PLoS Biology on 2025-02-07 14:00:00 UTC.
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Objective
To investigate the role of neuroinflammation in the substantia nigra pars compacta (SNc) across different parkinsonian disorders—Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA)—by examining SNc dopaminergic neuron counts, neuroinflammatory T cells, and microglial activity.
Methods
Postmortem neuropathological samples were collected from 79 individuals (PD, n = 38; PSP, n = 15; MSA, n = 14; controls, n = 12). The density of SNc tyrosine hydroxylase (TH)-positive neurons, T cells (CD3+, CD4+, and CD8+), and Iba1 expression (Iba1-positive microglia/macrophages) were examined in the SNc and crus cerebri. Demographic and clinical data were gathered from patient histories.
Results
PSP patients had 89 to 212% more nigral CD3+, CD4+, and CD8+ T cells compared to MSA patients (p < 0.04), 125 to 178% more CD3+ and CD4+ T cells than healthy controls (p < 0.002), and 95% more CD4+ T cells than PD patients (p = 0.001). Iba1 expression in the SNc was higher in PD patients than in MSA patients (p = 0.004), with no significant differences observed across other conditions. There was a negative association between disease duration and SNc CD3+ T cell density (p = 0.002), and a positive correlation between nigral dopaminergic neuron density and CD3+ density, CD8+ density, and Iba1 expression in PD patients.
Interpretation
The study reveals distinctive neuroinflammatory patterns in the SNc, with T cell-mediated inflammation prominent in PSP and microglia-mediated inflammation in PD. PSP and MSA show greater SNc dopaminergic neuron loss compared to PD. Increased neuroinflammatory response is seen in earlier disease stages, diminishing with greater neuron loss, which may inform disease progression understanding and therapeutic strategies. ANN NEUROL 2025
in Annals of Neurology on 2025-02-07 12:09:13 UTC.
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Background Machine learning and AI promise to revolutionize the way we leverage medical imaging data for improving care but require large datasets to train computational models that can be implemented in clinical practice. However, processing large and complex medical imaging datasets remains an open challenge. Methods To address this issue, we developed Med-ImageTools, a new Python open-source software package to automate data curation and processing while allowing researchers to share their data processing configurations more easily, lowering the barrier for other researchers to reproduce published works. Use cases We have demonstrated the efficiency of Med-ImageTools across three different datasets, resulting in significantly reduced processing times. Conclusions The AutoPipeline feature will improve the accessibility of raw clinical datasets on public archives, such as the Cancer Imaging Archive (TCIA), the largest public repository of cancer imaging, allowing machine learning researchers to process analysis-ready formats without requiring deep domain knowledge.
in F1000Research on 2025-02-07 08:19:24 UTC.
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Science, Volume 387, Issue 6734, February 2025.
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Science, Volume 387, Issue 6734, February 2025.
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Science, Volume 387, Issue 6734, February 2025.
in Science on 2025-02-07 08:00:00 UTC.
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Science, Volume 387, Issue 6734, February 2025.
in Science on 2025-02-07 08:00:00 UTC.
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Science, Volume 387, Issue 6734, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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Science Advances, Volume 11, Issue 6, February 2025.
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An et al. use an integrated metabolomic and transcriptomic approach in rats with liver-selective suppression of ChREBP to unveil metabolic functions of the transcription factor in multiple pathways, including nucleotide and CoA metabolism and amino acid and monocarboxylic acid transport.
in Cell Reports: Current Issue on 2025-02-07 00:00:00 UTC.
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Ravenhill et al. employ subcellular proteomics to quantify the movement of >9,000 proteins during infection with the model RNA virus Sendai. In addition to known controls, CRTC2 and CRTC3 translocate to the nucleus, triggering a transcriptional program that includes profibrogenic cytokine IL-11 and antiviral factor NR4A2.
in Cell Reports: Current Issue on 2025-02-07 00:00:00 UTC.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00391-x
Andrew Robinson reviews five of the best science picks.
in Nature on 2025-02-07 00:00:00 UTC.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00326-6
The apes can tailor their communications to account for a human partner’s level of knowledge.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00317-7
In episode 2 of What's in a name we look how choosing names can help, or hinder, attempts to communicate important messages.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00374-y
The mass-archiving effort is in response to the US Centers for Disease Control and Prevention removing some of its web pages.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00372-0
The American Society for Microbiology deleted terms such as equity from its website, sparking protests from members.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00396-6
The Howard Hughes Medical Institute, a huge funder of biomedical research, has cut a $60-million initiative to boost diversity in science education.
in Nature on 2025-02-07 00:00:00 UTC.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00406-7
The company’s AlphaGeometry2 reaches the level of gold-medal students in the International Mathematical Olympiad.
in Nature on 2025-02-07 00:00:00 UTC.
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Nature, Published online: 07 February 2025; doi:10.1038/d41586-025-00392-w
Researchers who investigate highly-politicized topics can face harassment, others for their race, gender identity or disability. Two scientists share their stories.
in Nature on 2025-02-07 00:00:00 UTC.
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Nature Photonics, Published online: 07 February 2025; doi:10.1038/s41566-025-01621-4
A miniaturized diffractive neural network is fabricated on the distal facet of a multimode fibre, allowing all-optical image transportation through the fibre. With a compact footprint of 150 μm × 150 μm, the system allows the transportation of images with a minimum feature size of 4.90 μm and shows transfer learning capabilities when transporting images of biological cells projected by spatial light modulators.
in Nature Photomics on 2025-02-07 00:00:00 UTC.
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Nature Physics, Published online: 07 February 2025; doi:10.1038/s41567-025-02816-w
Author Correction: Free-electron quantum optics
in Nature Physics on 2025-02-07 00:00:00 UTC.
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Nature Physics, Published online: 07 February 2025; doi:10.1038/s41567-024-02762-z
A unified description of the dynamics of structurally disordered materials is challenging. Simulations of model systems now show that percolation theory provides a framework unifying the two most prominent relaxation processes in supercooled liquids and glasses.
in Nature Physics on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04422-0
A Comprehensive Dataset on Microbiome Dynamics in Rheumatoid Arthritis from a Large-Scale Cohort Study
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04572-1
An EEG dataset for interictal epileptiform discharge with spatial distribution information
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04547-2
A single-nucleus RNA sequencing atlas of the postnatal retina of the shark Scyliorhinus canicula
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04552-5
Reach&Grasp: a multimodal dataset of the whole upper-limb during simple and complex movements
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04491-1
BenthicNet: A global compilation of seafloor images for deep learning applications
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Scientific Data, Published online: 07 February 2025; doi:10.1038/s41597-025-04548-1
An Integrated Database for Exploring Alternative Promoters in Animals
in Nature scientific data on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07620-z
Author Correction: Structure and function of a β-1,2-galactosidase from Bacteroides xylanisolvens, an intestinal bacterium
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07632-9
USP14 regulates PERIOD (PER) protein stability post-translationally in Drosophila via interaction with SLIMB, a protein involved in PER degradation, and Lys1117 and Lys1118 are key ubiquitination sites critical for maintaining PER stability.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07607-w
Inducible protein overexpression in stably transfected cells enables the acquisition of atomically resolved NMR spectra of proteins in human cells during specific cell cycle phases and in 3D human tissue models.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07475-4
Multiomics sheds light on the gene expression signature of the spinal cord during the ageing process-resistance to ferroptosis via the upregulation of Fth1.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07619-6
Functional characterization of PfFBXO1, utilizing cell biology, genetics, and biochemistry, demonstrates essential roles for this protein in formation of the inner membrane complex in asexual merozoites and sexual-stage gametocytes.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07593-z
SeqCas9, a Cas9 variant from the Streptococcus family, recognizes a simple NNG PAM with high activity and enhanced specificity, highlighting its potential as an efficient and precise tool for gene editing applications.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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Communications Biology, Published online: 07 February 2025; doi:10.1038/s42003-025-07575-1
Meta-analysis of mouse tauopathy data sheds light on the cell types that may be involved in conferring selected regional vulnerability to pathology.
in Nature communications biology on 2025-02-07 00:00:00 UTC.
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in eLife on 2025-02-07 00:00:00 UTC.
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Discovering new strategies to combat the multidrug-resistant bacteria constitutes a major medical challenge of our time. Previously, artesunate (AS) has been reported to exert antibacterial enhancement activity in combination with β-lactam antibiotics via inhibition of the efflux pump AcrB. However, combination of AS and colistin (COL) revealed a weak synergistic effect against a limited number of strains, and few studies have further explored its possible mechanism of synergistic action. In this article, we found that AS and EDTA could strikingly enhance the antibacterial effects of COL against mcr-1- and mcr-1+ Salmonella strains either in vitro or in vivo, when used in triple combination. The excellent bacteriostatic effect was primarily related to the increased cell membrane damage, accumulation of toxic compounds and inhibition of MCR-1. The potential binding sites of AS to MCR-1 (THR283, SER284, and TYR287) were critical for its inhibition of MCR-1 activity. Additionally, we also demonstrated that the CheA of chemosensory system and virulence-related protein SpvD were critical for the bacteriostatic synergistic effects of the triple combination. Selectively targeting CheA, SpvD, or MCR using the natural compound AS could be further investigated as an attractive strategy for the treatment of Salmonella infection. Collectively, our work opens new avenues toward the potentiation of COL and reveals an alternative drug combination strategy to overcome COL-resistant bacterial infections.
in eLife on 2025-02-07 00:00:00 UTC.
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Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL-6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.
in eLife on 2025-02-07 00:00:00 UTC.
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Recent studies showed an unexpected complexity of extracellular vesicle (EV) biogenesis pathways. We previously found evidence that human colorectal cancer cells in vivo release large multivesicular body-like structures en bloc. Here, we tested whether this large EV type is unique to colorectal cancer cells. We found that all cell types we studied (including different cell lines and cells in their original tissue environment) released multivesicular large EVs (MV-lEVs). We also demonstrated that upon spontaneous rupture of the limiting membrane of the MV-lEVs, their intraluminal vesicles (ILVs) escaped to the extracellular environment by a ‘torn bag mechanism’. We proved that the MV-lEVs were released by ectocytosis of amphisomes (hence, we termed them amphiectosomes). Both ILVs of amphiectosomes and small EVs separated from conditioned media were either exclusively CD63 or LC3B positive. According to our model, upon fusion of multivesicular bodies with autophagosomes, fragments of the autophagosomal inner membrane curl up to form LC3B positive ILVs of amphisomes, while CD63 positive small EVs are of multivesicular body origin. Our data suggest a novel common release mechanism for small EVs, distinct from the exocytosis of multivesicular bodies or amphisomes, as well as the small ectosome release pathway.
in eLife on 2025-02-07 00:00:00 UTC.
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Abstract
Neuroinflammation has been identified as an important pathological component of cognitive impairment, and translocator protein imaging has become a valuable tool for assessing its patterns. We aimed to obtain the exact distribution of neuroinflammation in cognitive impairment and its underlying mechanisms with amyloid-beta. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, two investigators searched literature databases for studies that measured translocator protein binding levels. This measurement was performed between healthy controls and subjects with mild cognitive impairment or Alzheimer’s disease via voxel-based positron emission tomography image analysis at the whole-brain level. This meta-analysis was performed with the anisotropic effect-size based algorithm. Neuroinflammation in patients with mild cognitive impairment was mainly concentrated in the left middle temporal gyrus and left amygdala. In Alzheimer’s disease patients, the brain regions involved were the left inferior temporal gyrus, left calcarine fissure/surrounding cortex, left parahippocampal gyrus, right lingual gyrus, and right middle temporal gyrus. In addition, neuroinflammation in patients with cognitive impairment was highly correlated with amyloid-beta deposition in the cortex. This study deepens our understanding of the patterns of neuroinflammation in patients with cognitive impairment and its interaction with amyloid-beta, providing potential insights for therapeutic approaches targeting neuroinflammation in Alzheimer’s disease.
in Cerebral Cortex on 2025-02-07 00:00:00 UTC.
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Abstract
Creativity is a multifaceted cognitive process that can be driven by either malevolent or benevolent intentions, leading to divergent social outcomes. There is still uncertainty about the similarities and differences in the underlying neural activities of creativity associated with malevolent and benevolent intentions. This study investigates how intentions shape creative ideation using functional magnetic resonance imaging during malevolent and benevolent creative tasks. Key findings include: (i) overlapping activation in the middle frontal gyrus and superior frontal gyrus across tasks, indicating a shared neural basis for creative thinking; (ii) distinct activation patterns, with the malevolent creative task showing greater activation and reduced functional connectivity in regions such as the right rolandic operculum and supramarginal gyrus compared to the benevolent creative task; (iii) similar neural activity patterns in regions like the middle frontal gyrus and lingual gyrus between the malevolent creative task and benevolent creative task may indicate overlapping cognitive processes. (iv) Correlations between task-specific neural activity and behavioral performance, including malevolence negatively correlating with functional connectivity in the rolandic operculum and middle cingulate cortex during the malevolent creative task, and benevolence correlating with functional connectivity in the parahippocampal gyrus and insula during the benevolent creative task. This study indicated distinct and shared neural correlates linked to malevolent and benevolent creativity.
in Cerebral Cortex on 2025-02-07 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 166: Prevalence and Clinical Correlates of Cerebrovascular Alterations in Fabry Disease: A Cross-Sectional Study
Brain Sciences doi: 10.3390/brainsci15020166
Authors:
Daniele Di Natale
Salvatore Rossi
Gianmarco Dalla Zanna
Antonio Funcis
Tommaso Filippo Nicoletti
Ludovico Luca Sicignano
Elena Verrecchia
Angela Romano
Maria Gabriella Vita
Naike Caraglia
Francesca Graziani
Federica Re
Gisella Guerrera
Luca Battistini
Gabriella Silvestri
Background/Objectives: Fabry disease (FD) is an inborn error of the glycosphingolipid metabolism with variable kidney, heart, and central nervous system (CNS) involvement. CNS-related FD manifestations include early ischemic stroke and white matter lesions (WMLs) related to cerebral small-vessel disease (CSVD), possibly resulting in cognitive impairment. We studied 40 adult FD patients (17 male) to assess: (i) prevalence of cerebrovascular and cognitive manifestations in FD and their correlation with heart and renal involvement; and (ii) the potential value of serum neurofilament light chain (NfL) levels as an indicator of WMLs in FD. Methods: Patients underwent detailed diagnostic assessment related to FD, also including Mainz Severity Score Index (MSSI), neuropsychological tests, brain MRI to assess WMLs by the modified Fazekas score (mFS), and NfL determination by single-molecule array (SiMoA) (n = 22 FD patients vs. 15 healthy controls). Results: Overall, 4 FD patients had a history of ischemic stroke and 13/32 patients (40.6%) had an mFS &ge; 1. Almost two-thirds of FD patients (27/39, 69.2%) showed impairment on at least one cognitive test. On univariate analysis, only a reduction in estimated glomerular filtration rate was associated with an increased likelihood of having WMLs on brain MRI. Serum NfL levels were higher in FD patients vs. controls, with a trend toward significance (p = 0.08). Conclusions: Mild-to-moderate CSVD is a characteristic brain &ldquo;signature&rdquo; in FD patients. Both cardiac and renal involvement correlate with WML load, but only renal involvement appears to be predictive of CNS damage. Brain microvascular damage is associated with mild cognitive impairment in FD, and serum NfL might represent a potential biomarker of CSVD in FD.
in Brain Sciences on 2025-02-07 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 165: Balneotherapy as a Complementary Intervention for Stress and Cortisol Reduction: Findings from a Randomized Controlled Trial
Brain Sciences doi: 10.3390/brainsci15020165
Authors:
Lolita Rapolienė
Dovydas Rapolis
Aelita Bredelytė
Giedrė Taletavičienė
Antonella Fioravanti
Arvydas Martinkėnas
Background: In our modern era, stress has become a pervasive challenge, affecting individuals across all ages and backgrounds. Acute or chronic stress and elevated cortisol levels are known to impair neurological function and hinder rehabilitation outcomes. Therefore, effective treatment methods that reduce stress, enhance mental health, and promote overall well-being are urgently needed. The aim of this study was to evaluate the seasonal impact of balneotherapy on distress, as measured by the General Symptoms Distress Scale (GSDS), and well-being, as assessed using the Arizona Integrative Outcomes Scale (AIOS), and the effect of winter balneotherapy on salivary cortisol levels. Methods: In 2023, a multicenter, single-blind, parallel-group, randomized controlled trial was carried out across six medical spa centers in Lithuania. Participants with a stress intensity greater than 3 points on the Visual Analogue Scale (VAS) underwent combined natural resource-based therapies over a 1- to 2-week treatment period. Outcomes were assessed using the General Symptom Distress and Arizona Integrative Outcomes scales, along with salivary cortisol measurements after winter intervention. Results: The results demonstrated a significant reduction in distress intensity by 1&ndash;3.5 points (VAS), with winter interventions showing greater efficacy compared to summer. Participants also experienced an increase in well-being by up to 3 points (VAS), improved stress management by up to 1.9 points (VAS), and a reduction in salivary cortisol levels by 0.9 units following winter-based treatments. Some gender differences emerged in specific groups. Conclusions: Our study provides robust evidence for the stress-reducing effects of balneotherapy, particularly highlighting the enhanced efficacy of winter interventions. These findings are especially relevant for neurological rehabilitation, where stress reduction and improved autonomic regulation can support neuroplasticity, recovery processes, and overall quality of life. This research offers valuable insights for developing holistic, seasonally optimized strategies to aid stress management and promote neurological health.
in Brain Sciences on 2025-02-07 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 164: Effect of N-Acetyl Cysteine as an Adjuvant Treatment in Alzheimer’s Disease
Brain Sciences doi: 10.3390/brainsci15020164
Authors:
Sarah Monserrat Lomelí Martínez
Fermín Paul Pacheco Moisés
Oscar Kurt Bitzer-Quintero
Javier Ramírez-Jirano
Daniela L. C. Delgado-Lara
Irán Cortés Trujillo
Juan Heriberto Torres Jasso
Joel Salazar-Flores
Erandis Dheni Torres-Sánchez
Oxidative stress levels are exacerbated in Alzheimer&rsquo;s disease (AD). This phenomenon feeds back into the overactivation of oxidase enzymes, mitochondrial dysfunction, and the formation of advanced glycation end-products (AGEs), with the stimulation of their receptors (RAGE). These factors stimulate A&beta; peptide aggregation and tau hyperphosphorylation through multiple pathways, which are addressed in this paper. The aim of this study was to evaluate the regulatory effect of N-acetyl cysteine (NAC) on oxidant/antioxidant balance as an adjuvant treatment in patients with AD. The results obtained showed that NAC supplementation produced improved cognitive performance, decreased levels of oxidative stress markers, lowered activities of oxidase enzymes, increased antioxidant responses, and attenuated inflammatory and apoptotic markers. Moreover, NAC reversed mitochondrial dysfunction, lowered AGEs-RAGE formation, attenuated A&beta; peptide oligomerization, and reduced phosphorylation of tau, thereby halting the formation of neurofibrillary tangles and the progression of AD.
in Brain Sciences on 2025-02-07 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 163: Clinical and Epidemiological Characteristics of Patients with Functional Stroke Mimics: A Case–Control Study from Southern Portugal
Brain Sciences doi: 10.3390/brainsci15020163
Authors:
Miguel Domingos
Vítor Hugo Silva
Sara Schuh
Helena Correia
Pedro Palma
João Pedroso Pedro
Bruno Vila Nova
Ana Marreiros
Ana Catarina Félix
Hipólito Nzwalo
Background: Patients with functional neurological disorder presenting as stroke mimics or functional stroke mimics (FSMs) pose significant diagnostic challenges. In the acute phase, especially when patients are present within the therapeutic window for acute reperfusion treatments, a misdiagnosis of FSM can lead to unnecessary and costly interventions. Despite its clinical importance, the literature on the risk factors for FSM is limited. This study aims to compare the clinical and epidemiological characteristics of patients with FSM to those with confirmed acute ischemic stroke (AIS). Methods: This case&ndash;control study involved temporal matching between consecutive series of patients with FSM and controls with AIS from a single tertiary university hospital in southern Portugal. Results: A total of 188 patients were included: 64 cases (FSM) and 188 controls (AIS). The rate of stroke code activation and use of ambulance between was comparable between the two groups. The group of patients with FSM was younger (53.2 years vs. 69.5 years, p &lt; 0.001) and had a higher proportion of females (52.4% vs. 47.6%, p = 0.001). There was no difference in terms of clinical severity at presentation. The proportion of specific signs, such as transcortical aphasia (3.1% vs. 20.9%, p = 0.014), gait abnormalities (15.6% vs. 33.9%, p = 0.004), and cranial nerve abnormalities (31.2% vs. 43.5%, p = 0.042), was lower in the FSM group compared to the AIS group. The proportion of patients on antithrombotic therapy (90.9% vs. 9.1%, p = 0.007) and antihypertensive drugs (78.5%, vs. 21.5%, p &lt; 0.001) prior to the event was significantly higher in the AIS group. Likewise, the prevalence of cerebrovascular risk factors such as diabetes mellitus (14.3% vs. 85.7%, p = 0.005), arterial hypertension (23.8% vs. 76.2%, p = 0.001), and smoking (43.7% vs. 56.3%, p = 0.005) was lower in the FSM group compared to the AIS group. No statistically significant differences were observed in cholesterol levels or the prevalence of dyslipidemia between the two groups. Psychiatric comorbidities, including generalized anxiety disorder (71.4% vs. 28.6%, p = 0.05) and major depressive disorder (61.9% vs. 28.1%, p = 0.01), were more prevalent in the FSM group. Conclusions: Patients with FSM display different clinical and epidemiological profiles, with a higher likelihood of being younger, female, having prior psychiatric conditions, and lacking traditional cerebrovascular risk factors.
in Brain Sciences on 2025-02-07 00:00:00 UTC.
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Brain Sciences, Vol. 15, Pages 162: Emergent Aspects of the Integration of Sensory and Motor Functions
Brain Sciences doi: 10.3390/brainsci15020162
Authors:
Tiziana M. Florio
This article delves into the intricate mechanisms underlying sensory integration in the executive control of movement, encompassing ideomotor activity, predictive capabilities, and motor control systems. It examines the interplay between motor and sensory functions, highlighting the role of the cortical and subcortical regions of the central nervous system in enhancing environmental interaction. The acquisition of motor skills, procedural memory, and the representation of actions in the brain are discussed emphasizing the significance of mental imagery and training in motor function. The development of this aspect of sensorimotor integration control can help to advance our understanding of the interactions between executive motor control, cortical mechanisms, and consciousness. Bridging theoretical insights with practical applications, it sets the stage for future innovations in clinical rehabilitation, assistive technology, and education. The ongoing exploration of these domains promises to uncover new pathways for enhancing human capability and well-being.
in Brain Sciences on 2025-02-07 00:00:00 UTC.
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The use of supervised machine learning to approximate poses in video recordings allows for rapid and efficient analysis of complex behavioral profiles. Currently, there are limited protocols for automated analysis of operant self-administration behavior. We provide a methodology to (1) obtain videos of training sessions via Raspberry Pi microcomputers or GoPro cameras, (2) obtain pose estimation data using the supervised machine learning software packages DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA) with a local high-performance computer cluster, (3) compare standard Med-PC lever response versus quadrant time data generated from pose estimation regions of interest, and (4) generate predictive behavioral classifiers. Overall, we demonstrate proof of concept to use pose estimation outputs from DLC to both generate quadrant time results and obtain behavioral classifiers from SimBA during operant training phases.
in eNeuro on 2025-02-06 17:30:14 UTC.
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A common impairment in aging is age-related hearing loss (presbycusis), which manifests as impaired spectrotemporal processing. Presbycusis can be caused by a dysfunction of the peripheral and central auditory system, and these dysfunctions might differ between the sexes. To date, the circuit mechanisms in the central nervous system responsible for age-related auditory dysfunction remain mostly unknown. In the auditory cortex (ACtx), aging is accompanied by alteration in normal inhibitory (GABA) neurotransmission and changes in excitatory (NMDA and AMPA) synapses, but which circuits are affected has been unclear. Here we investigated how auditory cortical microcircuits change with age and if sex-dependent differences existed. We performed laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings from layer (L) 2/3 cells in the primary auditory cortex (A1) in young adult (2–3 months) and aged (older than 18 months) male and female CBA/CaJ mice which have normal peripheral hearing. We found that L2/3 cells in aged male animals display functional hypoconnectivity of inhibitory circuits originating from L2/3 and L4. Compared with cells from young adult mice, cells from aged male mice have weaker excitatory connections from L2/3. We also observed an increased diversity of excitatory and inhibitory inputs. These results suggest a sex-specific reduction and diversification in excitatory and inhibitory intralaminar cortical circuits in aged mice compared with young adult animals. We speculate that these unbalanced changes in cortical circuits contribute to the functional manifestations of age-related hearing loss in both males and females.
in eNeuro on 2025-02-06 17:30:14 UTC.
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Abstract Background Nigella sativa L., known as black cumin, is thought to possess anti-inflammatory properties that may help alleviate related conditions. This study examined the effects of black cumin extract on levels of Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α), both inflammatory markers. Methods The experimental design included a control group used solely for post-testing. Five groups of Wistar rats were studied: a negative control group (N), a dyslipidemia group as a positive control (P), a dyslipidemia group given black cumin (P1), a dyslipidemia group treated with atorvastatin (P2), and a dyslipidemia group receiving both atorvastatin and black cumin (P3).IL-1β and TNF-α levels were measured using ELISA, and statistical analysis was conducted using ANOVA followed by the Duncan test. Results After treatment, the average IL-1β levels were 38.26 pg/mL (N), 102.16 pg/mL (P), 57.05 pg/mL (P1), 29.16 pg/mL (P2), and 54.06 pg/mL (P3). The Duncan test indicated no significant differences in IL-1β levels among groups N, P2, and P3 (p>0.05), while group P exhibited the highest IL-1β levels, significantly different from the others. For TNF-α, average levels post-treatment were 30.42 pg/mL (N), 22.02 pg/mL (P), 27.25 pg/mL (P1), 16.33 pg/mL (P2), and 13.29 pg/mL (P3). The Duncan test showed that group P3 had the lowest TNF-α levels, which were not significantly different from P2 (p>0.05) but significantly different from groups P, P1, and N (p<0.05). Conclusions In conclusion, black cumin extract effectively reduces IL-1β levels in high-fat diet rat models, while the combination of atorvastatin and black cumin extract yields the most significant reduction in TNF-α levels.
in F1000Research on 2025-02-06 16:24:44 UTC.
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Background Migration is a social determinant of health, and migrants often face health inequalities compared to host populations. Migrants are underrepresented in health research in many European countries, including Belgium, which is concerning. The World Health Organization (WHO) developed a comprehensive framework aimed at guiding research on migration and health within the WHO European Region. This initiative supports evidence-based policymaking among European member states by providing a foundational structure for examining various strategies and methodologies. The framework serves as a catalyst for discussion and critical analysis, contributing to the formulation of a global research agenda on migration and health under WHO’s leadership. Additionally, it outlines key research priorities and offers strategic recommendations to enhance the understanding and response to health issues related to migration. One of these recommendations calls on researchers to “maximise the use of existing data from research and routinely collected data in health information systems”. Objective The overarching aim of our Datahub initiative is to map available sources of datasets about access to and use of medicines among migrant populations, and test if and under which conditions they can be used in research, by taking the case of Flanders, Belgium. Methods This initiative will involve conducting a focused review to map datasets used for reporting access to and use of medicines among migrants, followed by a qualitative study with key informants; a structured analysis of ethical and legal challenges to be addressed when using the datasets we identified for research; and content description and evaluation of the different identified datasets. Results We assert that the results of our initiative will help presenting the diverse sources of data about medicines access or use among migrant populations. They will be also used to provide recommendations about enhancing the possibilities of retrieving, and using data, including recommendations for (legal, ethical, methodological) risk mitigation for retrieving and using these data.
in F1000Research on 2025-02-06 16:15:21 UTC.
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Background Hormonal changes in pregnancy and their induced effect on periodontal health are well documented. The present study is aimed at the potential repercussions of multiple pregnancies on periodontal health. Materials and methods Our study utilized data from key sections of the NHANES. All the pertaining and relevant data for the study is collected. Our exposure variable was the number of pregnancies, and the outcome variable was periodontal disease. The number of pregnancies is classified as one, two, three, four, or more. Age, gender, race/ethnicity, education, poverty/income ratio, marital status, and other variables. Multiple logistic regression models were employed to assess the impact of multiple pregnancies on periodontal disease. Result The crude and multiple logistic regression analyses revealed that none of the variables were significantly associated with the prevalence of periodontitis. In univariate analysis, patients with one or two pregnancies had higher odds of experiencing periodontitis (OR 1.154, 95% CI 0.748-1.779), (OR 1.464, 95% CI 0.864-2.483) respectively. However, these associations did not reach statistical significance. Conclusion Within the limitation of the study, there is no significant relationship between parity and the prevalence of periodontitis, the longitudinal study may be warranted to delve deeper into any potential associations.
in F1000Research on 2025-02-06 16:13:50 UTC.
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Abstract Background Polyetheretherketone (PEEK) is widely used in the biomedical field due to its outstanding biological and mechanical properties. Originally employed as a temporary abutment in implantology, recent research has expanded its indications for more definitive applications, such as frameworks and dental post and core. This shift requires a thorough assessment of PEEK’s adhesion and mechanical characteristics. However, PEEK’s inert properties and intricate chemistry create difficulties in surface treatment, resulting in reduced surface energy and inadequate adhesion. Various physical and chemical modification techniques, including acid etching (e.g., 98% sulfuric acid), sandblasting with alumina oxide (Al₂O₃), plasma treatment, laser irradiation, silanization, and air abrasion with silica-coated particles, have been proposed to enhance PEEK’s bonding performance. Despite its numerous clinical trials, standardized protocols remain lacking. This systematic review aims to assess the impact of surface treatments on the bonding performance of PEEK posts. Methods A detailed search of the literature will be conducted across several databases including PubMed, Scopus and clinical trial registries. Additional databases such as Cochrane Central, EMBASE, Web of Science and EBSCO will also be included. The search strategy will target controlled randomized studies and non-randomized clinical trials evaluating the impact of surface treatments on PEEK post adhesion strength. The Newcastle-Ottawa Scale (NOS) will be used to assess bias in non-randomized studies, while the Cochrane Risk of Bias (ROB II) tool will be employed for evaluating randomized controlled trials. Data extraction will focus on study design, treatment methods, outcomes and results. This systematic review protocol will adhere to the guidelines for systematic reviews outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Discussion The discussion will explore the implications of findings on clinical practice, highlighting the importance of enhancing PEEK’s bioactivity and surface energy to improve bonding efficacy in dental procedures. Moreover, it will suggest areas for future research to advance dental materials science, aiming to optimize the utilization of PEEK in dental applications Systematic review registration PROSPERO: CRD42024529783 (Registered on 08/04/2024).
in F1000Research on 2025-02-06 16:11:55 UTC.
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Background Recent studies have established that Medicinal Marijuana (MM) is beneficial in the treatment of spasms, sleep, and pain in adult patients with varying medical diagnoses and symptoms. However, MM has rarely been used for the treatment of Cerebral Palsy (CP) complications in adults. The aim of this literature review was to explore MM interventions globally, with a focus on identifying the best practice with MM for the treatment of complications of CP. Methods A literature search was performed using keywords and synonyms related to MM treatment and CP complications. Inclusions and exclusions were scoped to scholarly peer reviewed academic literature published 2019 to 2021 located in the Deakin Library collection. A screening process confirmed criteria adherence and identified additional papers in referencing. The papers were appraised and evaluated to ensure selections do not have perceived or actual bias. Results From 409 publications, 27 papers were selected for review because they investigated the benefits of MM treatment for patients with sleep, pain, and spasm complications. There was no literature found on the use of MM for adults with CP. Discussion Recent research has demonstrated that with an informed understanding of MM treatment adult patients with varying medical diagnoses and symptoms can use MM to manage sleep disruption and improve relaxation. Therefore, there are potential benefits for the use of MM in treating spasticity, pain, sleep and improvement of quality of life, and social and emotional wellbeing in adult patients with CP. No funding was sort or provided for this review and the results are specific to adults with CP, so they are not to be generalized to other populations.
in F1000Research on 2025-02-06 16:09:40 UTC.
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Elizabethkingia meningoseptica is an uncommon nosocomial pathogen that causes meningitis, pneumonia, and sepsis in neonates and in immunocompromised individuals. It exhibits resistance to many commonly employed first-line antibiotics used to treat gram-negative pathogens. Herein, we present three cases of late-onset sepsis with multi-drug resistant (MDR) Elizabethkingia meningoseptica in high-risk neonates. Case 1 was a one-day-old preterm low-birth-weight infant who presented with respiratory distress syndrome and septic shock. The patient was intubated and administered empirical broad-spectrum antibiotics and antifungal agents. Blood culture grew Candida krusei, hence Amphotericin B was initiated. Repeat blood culture on day 27 showed gram-negative bacilli, identified as Elizabethkingia meningoseptica by MALDI-TOF . Antibiotic susceptibility testing (AST) revealed resistance to Piperacillin/Tazobactam, but sensitivity to Vancomycin, Levofloxacin, and Minocycline. IV Vancomycin was administered, which resulted in clinical improvement and negative blood culture results. Case 2 was an eleven-day-old preterm, low-birth-weight baby who presented with fever. Initial investigations revealed normal complete blood counts (CBC) parameters and elevated CRP levels. Blood and CSF cultures isolated Elizabethkingia meningoseptica with a similar AST pattern. Intravenous Ciprofloxacin was initiated with clinical improvement and negative follow-up blood cultures. Case 3 was a one-day-old preterm baby, appropriate-to-gestational age, presenting with respiratory distress syndrome. The infant was intubated and started on inotropic support and intravenous antibiotics. Blood cultures on day 4 showed Elizabethkingia meningoseptica and Vancomycin was started. Follow-up cultures on days 6 and 14 grew Acinetobacter baumannii. A combination of Levofloxacin and Colistin was added, and blood cultures were negative after seven days, with clinical improvement. Elizabethkingia meningoseptica is a significant cause of hospital-acquired infections, especially in Neonatal Intensive Care Unit (NICU), leading to outbreaks. Clinicians must have a high degree of suspicion of E. meningoseptica for gram-negative bacilli causing sepsis and meningitis in high-risk patients. Recent technological advances have enabled accurate speciation to guide therapy and reduce morbidity and mortality rates.
in F1000Research on 2025-02-06 16:07:51 UTC.
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Bacillus velezensis is a bacterium widely recognized for its biocontrol properties and ability to promote plant growth. This study presents the whole-genome sequence of B. velezensis B26, a newly identified strain isolated from chicken carcass soil in Udupi, India. The bacterium showed strong activity against fungal pathogens and exhibited diverse enzymatic activities. The whole-genome sequencing was executed using Illumina technologies. Assembly revealed that strain B26 possesses a genome of 3,946,698-bp with a G+C content of 46.3%. Genome annotation identified 3776 protein-coding genes, 1 rRNA gene, 50 tRNA genes, 5 ncRNA genes, and 59 pseudogenes. Functional analysis of the B. velezensis B26 genome revealed 216 genes involved in carbohydrate metabolism, 3 genes in potassium metabolism, 148 genes linked for cofactors, vitamins, prosthetic groups and pigments, 10 genes involved in phosphorus metabolism, 24 genes associated with iron acquisition and metabolism, 20 genes for nitrogen metabolism, 6 genes involved in sulfur metabolism, 6 genes in secondary metabolism, 12 genes associated with metabolism of aromatic compounds, 43 genes involved in stress response and 36 genes associated with virulence, disease and defence. The raw sequence data generated in this work have been deposited in the NCBI database and the genome sequence is available under the accession number JAYKOV000000000. These genomic data provide insight into the biocontrol ability and plant-growth promoting capabilities of B. velezensis B26.
in F1000Research on 2025-02-06 16:02:24 UTC.
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Background Multiplayer Virtual Reality-Based Simulations (MPVR-based simulations) with immersive 3D environments have become an important tool in interprofessional education (IPE). However, instruments to measure interprofessional socialization in MPVR-based education are limited. The Interprofessional Socialization and Valuing Scale (ISVS) is a useful tool for evaluating interprofessional socialization. This pilot study aimed to adapt and validate the ISVS-24 for use in interprofessional MPVR-based simulations settings. Methods Seventy-two participants, including anesthesiology residents (at novice, junior, and senior levels), general physicians, and nurses, were recruited voluntarily. The ISVS-24 was cross-culturally adapted and reviewed by experts for content validity in the MPVR simulation context. Participants completed the adapted ISVS after undergoing an interprofessional MPVR-based simulation. Structural validity was assessed using factorial analysis through principal component analysis. Content validity was measured using the mean content validity index (CVI). Consistency validity was evaluated with Pearson correlation coefficients (PCC), and reliability was assessed using Cronbach’s alpha. Results The Kaiser-Meyer-Olkin test indicated sampling adequacy (0.885), and Bartlett’s sphericity test was significant (χ2(42) = 472.725, p < 0.05). A three-section structure was confirmed. The mean CVI was 0.815, with 21 valid items (Aiken’s V ≥ 0.5). Among the 72 respondents, 40 were female (55.6%) and 32 were male (44.4%); 26 were anesthesiology residents (36.1%), 23 were general physicians (31.9%), and 23 were nurses (31.9%). The overall Cronbach’s alpha was 0.959. PCC for all items exceeded the r table value (> 0.232) with p < 0.05, showing significant item relationships. Conclusions The adapted version of ISVS for MPVR simulation-based education has good validity and reliability to assess interprofessional socialization in an MPVR-based simulation setting.
in F1000Research on 2025-02-06 15:58:51 UTC.
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Objective Toluene is the most abundant lipophilic aromatic compound in our environment. Exposure to toluene through inhalation is toxic to the cardiovascular system due to the formation of reactive oxygen species (ROS) that trigger oxidative stress. This study aims to examine the response of coronary arteries to toluene inhalation exposure based on the expression of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), vascular cell adhesion molecule-1 (VCAM-1) in coronary arteries, and levels of CYP2E1 with oxidized low-density lipoprotein (Ox-LDL) in the serum. Methods This was a true experimental study on Wistar rats with a post-test control group design. In total, 36 Wistar rats were divided into five experimental (X1–X5) and one control group. The experimental groups were exposed to 1.6, 3.2, 6.4, 12.8, and 25.6 mL of toluene, respectively. All groups, except control, received inhalation exposure for 14 d (6 h/d). Results In Wistar rats, toluene exposure significantly reduced the expression of SOD and CAT enzymes while it increased the expression of MDA and VCAM-1 in the coronary artery. Serum levels of CYP2E1 and Ox-LDL were unaffected. Conclusion Acute inhalation exposure to toluene significantly decreased SOD and CAT expression with increased MDA and VCAM-1 expression in coronary arteries. Other findings suggest that decreased CAT expression leads to increased VCAM-1 expression in the coronary artery.
in F1000Research on 2025-02-06 15:56:38 UTC.
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In 2009 a review of the state of child and adolescent physical and mental health care in the United States, appeared hopeful with the possibility of addressing the unmet health needs of our nation’s children in schools (Manning, 2009). Major legislation and sweeping strides for addressing the affordability of health care in the United States with The Affordable Care Act (ACA) which was codified into law and signed by President Obama, opening the possibility that the unmet physical and mental health needs of America’s youth may be reduced through the availability and affordability of health insurance for everyone (Patient Protection and Affordable Care Act, 2010). Over the past 15 years, the health and mental health of children and adolescents in the United States have undergone notable changes, reflecting both progress and persistent challenges. While public health initiatives and policy advancements have improved access to care and contributed to reductions in asthma prevalence and teen pregnancy rates, other areas continue to demonstrate systemic challenges. The rising incidence of obesity, Type 2 diabetes, depression, suicidality and ADHD highlight the ongoing need for comprehensive health interventions at the public health level. Additionally, disparities in healthcare access, particularly among rural and low-income populations, remain significant barriers to the overall well-being of children and youth. The shortage of primary care providers, gaps in insurance coverage and the increasing burden on school-based health clinics further complicate care accessibility. This paper examines the evolving trends in child and adolescent health, emphasizing the critical role of policy, environmental changes and healthcare innovations in shaping outcomes. After almost 15 years of this call to action and implementation of the ACA we have made strides towards healthy outcomes for children and youth, evidencing that transformative, systemic change is not only possible, but necessary to ensure the well-being of future generations.
in F1000Research on 2025-02-06 15:07:29 UTC.
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by Rodrigo Osuna-Orozco, Edward Castillo, Kameron Decker Harris, Samantha R. Santacruz
Large-scale recordings of neural activity over broad anatomical areas with high spatial and temporal resolution are increasingly common in modern experimental neuroscience. Recently, recurrent switching dynamical systems have been used to tackle the scale and complexity of these data. However, an important challenge remains in providing insights into the existence and structure of recurrent linear dynamics in neural time series data. Here we test a scalable approach to time-varying autoregression with low-rank tensors to recover the recurrent dynamics in stochastic neural mass models with multiple stable attractors. We demonstrate that the parsimonious representation of time-varying system matrices in terms of temporal modes can recover the attractor structure of simple systems via clustering. We then consider simulations based on a human brain connectivity matrix in high and low global connection strength regimes, and reveal the hierarchical clustering structure of the dynamics. Finally, we explain the impact of the forecast time delay on the estimation of the underlying rank and temporal variability of the time series dynamics. This study illustrates that prediction error minimization is not sufficient to recover meaningful dynamic structure and that it is crucial to account for the three key timescales arising from dynamics, noise processes, and attractor switching.
in PLoS Computational Biology on 2025-02-06 14:00:00 UTC.
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by Dennis Khodasevich, Nina Holland, Lars van der Laan, Andres Cardenas
Background DNA methylation (DNAm) provides a window to characterize the impacts of environmental exposures and the biological aging process. Epigenetic clocks are often trained on DNAm using penalized regression of CpG sites, but recent evidence suggests potential benefits of training epigenetic predictors on principal components.
Methodology/findings We developed a pipeline to simultaneously train three epigenetic predictors; a traditional CpG Clock, a PCA Clock, and a SuperLearner PCA Clock (SL PCA). We gathered publicly available DNAm datasets to generate i) a novel childhood epigenetic clock, ii) a reconstructed Hannum adult blood clock, and iii) as a proof of concept, a predictor of polybrominated biphenyl exposure using the three developmental methodologies. We used correlation coefficients and median absolute error to assess fit between predicted and observed measures, as well as agreement between duplicates. The SL PCA clocks improved fit with observed phenotypes relative to the PCA clocks or CpG clocks across several datasets. We found evidence for higher agreement between duplicate samples run on alternate DNAm arrays when using SL PCA clocks relative to traditional methods. Analyses examining associations between relevant exposures and epigenetic age acceleration (EAA) produced more precise effect estimates when using predictions derived from SL PCA clocks.
Conclusions We introduce a novel method for the development of DNAm-based predictors that combines the improved reliability conferred by training on principal components with advanced ensemble-based machine learning. Coupling SuperLearner with PCA in the predictor development process may be especially relevant for studies with longitudinal designs utilizing multiple array types, as well as for the development of predictors of more complex phenotypic traits.
in PLoS Computational Biology on 2025-02-06 14:00:00 UTC.
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by Lucas D. Serdar, Jacob R. Egol, Brad Lackford, Brian D. Bennett, Guang Hu, Debra L. Silver
RNA abundance is controlled by rates of synthesis and degradation. Although mis-regulation of RNA turnover is linked to neurodevelopmental disorders, how it contributes to cortical development is largely unknown. Here, we discover the landscape of RNA stability regulation in the cerebral cortex and demonstrate that intact RNA decay machinery is essential for corticogenesis in vivo. We use SLAM-seq to measure RNA half-lives transcriptome-wide across multiple stages of cortical development. Leveraging these data, we discover cis-acting features associated with RNA stability and probe the relationship between RNA half-life and developmental expression changes. Notably, RNAs that are up-regulated across development tend to be more stable, while down-regulated RNAs are less stable. Using compound mouse genetics, we discover CNOT3, a core component of the CCR4-NOT deadenylase complex linked to neurodevelopmental disease, is essential for cortical development. Conditional knockout of Cnot3 in neural progenitors and their progeny in the developing mouse cortex leads to severe microcephaly due to altered cell fate and p53-dependent apoptosis. Finally, we define the molecular targets of CNOT3, revealing it controls expression of poorly expressed, non-optimal mRNAs in the cortex, including cell cycle-related transcripts. Collectively, our findings demonstrate that fine-tuned control of RNA turnover is crucial for brain development.
in PLoS Biology on 2025-02-06 14:00:00 UTC.
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by Eléa A. Renaud, Ambre J. M. Maupin, Laurence Berry, Julie Bals, Yann Bordat, Vincent Demolombe, Valérie Rofidal, Florence Vignols, Sébastien Besteiro
Several key cellular functions depend on proteins harboring an iron–sulfur (Fe-S) cofactor. As these Fe-S proteins localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are Fe-S cluster synthesis pathways localizing to the cytosol, but also present in the mitochondrion and in the chloroplast, 2 organelles of endosymbiotic origin. Toxoplasma gondii is a plastid-bearing parasitic protist responsible for a pathology affecting humans and other warm-blooded vertebrates. We have characterized the Toxoplasma homolog of HCF101, originally identified in plants as a protein transferring Fe-S clusters to photosystem I subunits in the chloroplast. Contrarily to plants, we have shown that HCF101 does not localize to the plastid in parasites, but instead is an important component of the cytosolic Fe-S assembly (CIA) pathway which is vital for Toxoplasma. While the CIA pathway is widely conserved in eukaryotes, it is the first time the involvement of HCF101 in this pan-eukaryotic machinery is established. Moreover, as this protein is essential for parasite viability and absent from its mammalian hosts, it constitutes a novel and promising potential drug target.
in PLoS Biology on 2025-02-06 14:00:00 UTC.
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by Ya Wang, Chun Hin Chow, Yu Zhang, Mengjia Huang, Randa Higazy, Neeraja Ramakrishnan, Lili Chen, Xuhui Chen, Yixiang Deng, Sheng Wang, Cuntai Zhang, Cong Ma, Shuzo Sugita, Shangbang Gao
The balance between synaptic excitation and inhibition (E/I) is essential for coordinating motor behavior, yet the differential roles of exocytosis regulators in this balance are less understood. In this study, we investigated the roles of 2 conserved exocytosis regulators, complexin/CPX-1 and CAPS/UNC-31, in excitatory versus inhibitory synapses at Caenorhabditis elegans neuromuscular junctions. cpx-1 null mutants exhibited a marked increase in spontaneous release specifically at excitatory synapses, alongside an unequal reduction in excitatory and inhibitory evoked release. A clamping-specific knockin mutant, cpx-1(Δ12), which preserved evoked release, also showed a biased enhancement in excitatory spontaneous release. Conversely, the unc-31 null mutation, while maintaining normal spontaneous release, displayed a more pronounced reduction in evoked release at excitatory synapses. Notably, we found that CPX-1’s clamping function is dependent on UNC-31 and is sensitive to external Ca2+. Pull-down experiments confirmed that CAPS/UNC-31 does not directly interact with complexin, implying an indirect regulatory mechanism. Moreover, complexin regulates activity-dependent synaptic plasticity, which is also UNC-31 dependent. The unexpected role of CAPS/UNC-31 in the absence of CPX-1 clamping function may underpin the synaptic E/I balance and coordinated behavioral outputs in different species.
in PLoS Biology on 2025-02-06 14:00:00 UTC.
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by Julie Y. Chen, Kyle M. Loh
An important question is whether the placenta is a source of, or merely a niche for, blood-forming hematopoietic stem cells. A recent PLOS Biology study suggests that the placenta does not directly give rise to hematopoietic stem cells.
in PLoS Biology on 2025-02-06 14:00:00 UTC.
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Analysis of the porcine cingulate sulcus was conducted using immunohistochemical techniques. Results showed a higher neuronal density within the depths of the cingulate sulcus (fundus), as well as decreased distance between neuronal cell bodies within the different cortical layers of the fundus.
ABSTRACT
Cortical folding (gyrification) is a unique process by which the brain can expand and increase surface area while confined by the boundaries of the inner wall of the skull. Although there is still much debate about the exact mechanisms concerning the genetic and cellular factors involved in this process, gyrification results in a heterogenous organization of neuronal layering and cell types not seen in the smooth, lissencephalic brain of rodents. In this article, we describe differences in neuronal density and supporting cells within the depths (fundus) and adjacent walls of the cingulate sulcus of the porcine brain. We also measured the distance between pyramidal neurons within Layers III and V to investigate if the observed increase in density of neurons within the cingulate fundus is associated with a decrease in distance between neurons in these layers. We also identify the presence of the gigantopyramidal neuron within the fundus of the porcine cingulate sulcus, a pyramidal neuron subtype seen in nonhuman primates and human brains. Taken together, this article provides evidence that further supports the heterogeneous composition of the gyrified brain by describing the cellular organization of the porcine cingulate sulcus.
in Journal of Comparative Neurology on 2025-02-06 11:11:46 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 6, February 2025.
SignificanceThe neural representation of time has long intrigued neuroscientists, particularly how it adapts to cognitive demands. Depending on the task, the brain encodes time either categorically (“long” or “short”) or as precise intervals. While the ...
in PNAS on 2025-02-06 08:00:00 UTC.
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Science, Volume 387, Issue 6734, Page 584-584, February 2025.
in Science on 2025-02-06 06:58:27 UTC.
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Science, Volume 387, Issue 6734, Page 585-585, February 2025.
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Science, Volume 387, Issue 6734, February 2025.
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Science, Volume 387, Issue 6734, Page 630-636, February 2025.
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Science, Volume 387, Issue 6734, Page 637-643, February 2025.
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Science, Volume 387, Issue 6734, Page 682-688, February 2025.
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Science, Volume 387, Issue 6734, Page 674-682, February 2025.
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Science, Volume 387, Issue 6734, Page 588-589, February 2025.
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Science, Volume 387, Issue 6734, Page 601-609, February 2025.
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Science, Volume 387, Issue 6734, Page 609-615, February 2025.
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Science, Volume 387, Issue 6734, Page 623-624, February 2025.
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Science, Volume 387, Issue 6734, Page 580-580, February 2025.
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Science, Volume 387, Issue 6734, Page 581-582, February 2025.
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Science, Volume 387, Issue 6734, Page 586-587, February 2025.
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Science, Volume 387, Issue 6734, Page 587-587, February 2025.
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Science, Volume 387, Issue 6734, Page 586-586, February 2025.
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Science, Volume 387, Issue 6734, Page 598-600, February 2025.
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Science, Volume 387, Issue 6734, Page 622-624, February 2025.
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Gautam, Duari et al. developed scCamAge, an AI tool for predicting cell age and age-related bioactivities from micrographs. scCamAge uses the joint representation of image features, cell-shape measurements, and inferred bioactivities. scCamAge was validated for its cross-species applicability and is available as an open-source resource for the community.
in Cell Reports: Current Issue on 2025-02-06 00:00:00 UTC.
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Zhang et al. report that MAIT cells protect against sterile lung injury by promoting cDC1 accumulation, which limits tissue damage through a DNGR-1-dependent pathway. Analysis of human IPF data suggests that MAIT cells may potentially modulate fibrosis.
in Cell Reports: Current Issue on 2025-02-06 00:00:00 UTC.
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Tolve et al. demonstrate that AP-2 stabilizes GRID2IP to regulate synaptic function in Purkinje cells. Loss of AP-2 disrupts synaptic connectivity, alters network activity, and impacts motor coordination. This study highlights the importance of AP-2 in cerebellar function and its implications for neurodegenerative disorders.
in Cell Reports: Current Issue on 2025-02-06 00:00:00 UTC.
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Shen et al. documented that PRMT7 is a functional target of SCZ risk SNPs at 16q22.1. They further uncovered that PRMT7 dysregulation resulted in NPC function defects by impacting the expression of genes related to the cell cycle and neuronal function, potentially contributing to the risk of SCZ.
in Cell Reports: Current Issue on 2025-02-06 00:00:00 UTC.
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Nature, Published online: 06 February 2025; doi:10.1038/s41586-025-08713-9
Granzyme K activates the entire complement cascade
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00386-8
Insights from probing the shock-absorbing layer within the crustacean’s club-like claw could inspire the design of tough new materials.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00325-7
A Copper Age burial in Spain holds the largest collection of beads ever found ― enough to require a tonne of shellfish as raw material.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00237-6
Process turns out eggs with delectable texture and high nutritional value.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00209-w
A five-step guide to communicating your science ethically and accurately.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00389-5
The first pig-organ transplant trial in humans has been approved. Plus, the internet doesn't affect our memories, but AI might.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00160-w
Researchers in Gaza tell Nature of ‘unwavering commitment to education and knowledge’ as most universities lie damaged or destroyed.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00363-1
Two brain regions work together when mice learn to override the instinct to run and hide from a potential threat.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00377-9
The model produces cited, pages-long reports that might be helpful for generating literature reviews.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00375-x
Microbes that reside peaceably in the nasal passageways and on the skin can be harnessed for taking drugs to target cells.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00385-9
Abrupt changes to programmes including USAID inhibit global efforts to stop disease such as HIV, malaria and more, say researchers.
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Nature, Published online: 06 February 2025; doi:10.1038/d41586-025-00376-w
Drug companies are trialling a host of medications that they hope will offer benefits beyond weight loss.
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Nature Neuroscience, Published online: 06 February 2025; doi:10.1038/s41593-025-01886-6
Non-REM sleep substates separate old and new memories
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Nature Neuroscience, Published online: 06 February 2025; doi:10.1038/s41593-025-01887-5
Prenatal stress effects on the placenta
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Nature Neuroscience, Published online: 06 February 2025; doi:10.1038/s41593-025-01885-7
Charting the development of human dorsal root ganglia
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Nature Reviews Neuroscience, Published online: 06 February 2025; doi:10.1038/s41583-025-00906-5
During vertebrate embryonic development, the spinal cord emerges from the posterior portion of the neural tube. Saade and Martí describe the complex series of morphogenetic events that shape the neural tube and the cellular and molecular mechanisms that regulate the formation of the embryonic spinal cord.
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Nature Methods, Published online: 06 February 2025; doi:10.1038/s41592-025-02599-1
DeepPrep is a preprocessing pipeline for functional and structural MRI data from humans. Deep learning-based modules and an efficient workflow allow DeepPrep to handle large datasets.
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Nature Methods, Published online: 06 February 2025; doi:10.1038/s41592-024-02590-2
Rhobo6 is a cell-impermeable small-molecule fluorophore that displays reversible fluorogenic binding to glycans, making it a general, wash-free, and non-perturbative label for the extracellular matrix in living samples.
in Nature Methods on 2025-02-06 00:00:00 UTC.
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The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action of the diffusible exotoxin, mycolactone. However, its role in the clinically evident vascular component of disease aetiology remains poorly explained. We have now dissected mycolactone’s effects on human primary vascular endothelial cells in vitro. We show that mycolactone-induced changes in endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven by rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis, combined with a reduction in the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disrupted in vivo during M. ulcerans infection in the mouse model. Remarkably, exogenous addition of laminin-511 reduced endothelial cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone. Hence supplementing mycolactone-depleted extracellular matrix may be a future therapeutic avenue, to improve wound healing rates.
in eLife on 2025-02-06 00:00:00 UTC.