bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially Resolved Gene Expression is Not Necessary for Identifying Spatial Domains
Authors: Lin Senlin , Zhao Yi , Yuan Zhiyuan 
Published: October 2023

AbstractThe development of Spatially Resolved Transcriptomics (SRT) technologies has revolutionized the study of tissue organization. We introduce a graph convolutional network with an attention and positive emphasis mechanism, named “BINARY,” relying exclusively on binarized SRT data to delineate spatial domains. BINARY outperforms existing methods across various SRT data types while using significantly less input information. Our study suggests that precise gene expression quantification may not always be essential, inspiring further exploration of the broader applications of spatially resolved binarized gene expression data.
PAK1 and NF2/Merlin jointly drive myelination by remodeling actin cytoskeleton in oligodendrocytes
Authors: Baudouin Lucas , Adès Noémie , Kanté Kadia , Bachelin Corinne , Hmidan Hatem , Deboux Cyrille , Panic Radmila , Messaoud Rémy Ben , Velut Yoan , Hamada Soumia , Pionneau Cédric , Duarte Kévin , Poëa-Guyon Sandrine , Barnier Jean-Vianney , Oumesmar Brahim Nait , Bouslama-Oueghlani Lamia 
Published: October 2023

AbstractIn the central nervous system (CNS), myelin formation by oligodendrocytes (OLs) relies on actin dynamics. Actin polymerization supports the ensheathment step, when the OL process contacts the axon, while a drastic shift to actin depolymerization is required to enable the following step of wrapping and expansion of myelin membranes. The molecular mechanisms triggering this switch, essential for proper myelination, have yet to be elucidated. Here, we identify P21-activated kinase 1 (PAK1) as a major regulator of actin depolymerization in OLs. We show that PAK1 accumulates in OLs in a kinase inhibited form, triggering actin disassembly and, consequently, myelin expansion. Remarkably, we identify NF2/Merlin as an endogenous inhibitor of PAK1 by proteomics analysis of its binding partners. We found thatNf2knockdown in OLs results in PAK1 activation and impairs myelin formation, and that pharmacological inhibition of PAK1 inNf2-knockdown OLs rescues these defects. Moreover, we demonstrate that modulating PAK1 activity in OLs controls myelin expansion and provide compelling evidence indicating that specificPak1loss-of-function in oligodendroglia stimulates the thickening of myelin sheathsin vivo. Overall, our data indicate that PAK1-NF2/Merlin duo plays a key role in actin cytoskeleton remodeling in OLs, required for proper myelin formation. These findings have broad mechanistic and therapeutic implications for demyelinating diseases and neurodevelopmental disorders.SignificanceRemodeling actin cytoskeleton plays a crucial role in myelin formation by oligodendrocytes (OLs). Recent studies have shown that expansion and wrapping of myelin membranes around axons depends on actin depolymerization. However, the molecular mechanisms triggering this key step in myelination are not fully elucidated. Using genetic and pharmacological tools as well as proteomics analyses, we found that PAK1 (P21 Activated Kinase 1) kinase activity is maintained inhibited by NF2/Merlin in OLs to allow actin depolymerization and, consequently, myelin membrane expansion.Pak1loss-of-function in OLs leads to an increase in myelin thickness in the white matter of adult mice, confirming the role of PAK1 inactivation in myelin membrane expansion.
Gastrulation-stage gene expression inNipbl+/-mouse embryos foreshadows the development of syndromic birth defects
Authors: Chea Stephenson , Kreger Jesse , Lopez-Burks Martha E. , MacLean Adam L. , Lander Arthur D. , Calof Anne L. 
Published: October 2023

AbstractIn animal models,Nipbl-deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange Syndrome (CdLS), the most common cause of which isNipbl-haploinsufficiency. Previous studies inNipbl+/-mice suggested that heart development is abnormal as soon as cardiogenic tissue is formed. To investigate this, we performed single-cell RNA-sequencing on wildtype (WT) andNipbl+/-mouse embryos at gastrulation and early cardiac crescent stages.Nipbl+/-embryos had fewer mesoderm cells than WT and altered proportions of mesodermal cell subpopulations. These findings were associated with underexpression of genes implicated in driving specific mesodermal lineages. In addition,Nanogwas found to be overexpressed in all germ layers, and many gene expression changes observed inNipbl+/-embryos could be attributed toNanogoverexpression. These findings establish a link betweenNipbl-deficiency,Nanogoverexpression, and gene expression dysregulation/lineage misallocation, which ultimately manifest as birth defects inNipbl+/-animals and CdLS.TeaserGene expression changes during gastrulation ofNipbl-deficient mice shed light on early origins of structural birth defects.
Length measurement of cholinergic innervation in the tunica albuginea of rat testis
Authors: Santamaría Luis , Ingelmo Ildefonso 
Published: October 2023

AbstractThe testicular albuginea is not a simple receptacle that contains the testis parenchyma. It is a biologically active structure involved, among other things, in the progression of sperm from the seminiferous tubules to the rete testis. This function, attributed to the albuginea myofibroblasts’ contractile properties, is mediated by its vegetative innervation. Therefore, the quantification of innervation seems relevant to deepen the knowledge of the testicular envelope’s physiology. The albuginea contains cholinergic nerve fibers that are not very evident and with a marked directional arrangement (anisotropy). These structural characteristics require that the quantification of the fibers’ length be carried out using stereological measurements, which ensure the absence of bias in the process. The authors have developed stereological tools usually carried out on vertical VUR (vertical uniform random) sections in the present work. This approach’s novelty is that the albuginea is treated "in toto" as if it were a thick section (slice) on which a cycloid grid is applied through different optical planes. Thus, on a pilot study of three specimens, cholinergic nerve fibers’ length density was estimated, as well as the estimates of the coefficient of error of measurements and the biological variability of the sample.Furthermore, after estimating the albuginea volume, the mean of the fibers’ absolute length can be obtained. This stereological approach can be used after visualization of the immunostained nerve fibers for various markers, as long as the reagents’ penetration into the tissue is ensured. Moreover, it can be used in other biological structures, such as the intestine of small animals, which can also be processed as whole mounts and treated as thick VUR sections.
Drosophila Bchsoverexpression recapitulates humanWDFY3neurodevelopmental phenotypes with implications for glial cell involvement in altered head circumference
Authors: Körner Marek B. , Velluva Akhil , Bundalian Linnaeus , Krohn Knut , Schön Kathleen , Schumann Isabell , Kromp Jessica , Thum Andreas S. , Garten Antje , Hentschel Julia , Jamra Rami Abou , Mrestani Achmed , Scholz Nicole , Langenhan Tobias , Le Duc Diana 
Published: October 2023

AbstractThe autophagy adaptorWDFY3is linked to neurodevelopmental delay and altered brain size. Loss-of-function variants are associated with an increased brain size in both humans and mice. We thus, hypothesized that the microcephaly observed in some of the patients may be related to a gain-of-function of theWDFY3gene product. While the role ofWDFY3loss-of-function has been studied extensively in neurons, little is known about the effects ofWDFY3overexpression in different neural cell types. We utilized aDrosophila melanogasteroverexpression model to investigate the effect of theWDFY3orthologBchs(blue cheese) on development, CNS size, and gene expression profiles. Glial and neuronal overexpression ofBchsimpaired CNS development, locomotion and autophagy. Glial overexpression ofBchsalso altered CNS size significantly. We identified 79 genes that were differentially expressed and overlapped in flies that overexpressBchsin glial and neuronal cells, respectively. Additionally, upon neuronalBchsoverexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondria. Our data indicate thatWDFY3/Bchsoverexpression in both neurons and glial cells results in impaired neural development, which corresponds to symptoms observed inWDFY3-related neurodevelopmental delay.
A control policy can be adapted to task demands during both motor execution and motor planning
Authors: Orban de Xivry Jean-Jacques , Hardwick Robert 
Published: October 2023

AbstractMovement planning consists of several processes related to the preparation of a movement such as decision making, target selection, application of task demands, action selection and specification of movement kinematics. These numerous processes are reflected in the reaction time, which is the time that it takes to start executing the movement. However, not all the processes that lead to motor planning increase reaction time. In this paper, we wanted to test whether tuning the control policy to task demands contributes to reaction time. Taking into account that the tuning of the control policy differs for narrow and wide targets, we used a timed response paradigm in order to track the amount of time needed to tune the control policy appropriately to task demands. We discovered that it does not take any time during motor planning and even that it can occur indistinguishably during motor planning or during motor execution. That is, the tuning the control policy was equally good when the narrow or wide target was displayed before than when it was displayed after the start of the movement. These results suggest that the frontier between motor planning and execution is not as clear cut as it is often depicted.New & NoteworthyMovement preparation consists of different processes such as target selection, and movement parameters selection. We investigate the time that it takes to tune movement parameters to task demands. We found that the brain does this instantaneously and that this can even happen during movement. Therefore, this suggests that there exists an overlap during movement planning and execution.
DEGRADATIVE POTENTIALS OF BACTERIA ISOLATED FROM CRUDE OIL CONTAMINATED SOIL
Authors: Augustine Jennifer Ada 
Published: October 2023

ABSTRACTPetroleum and its products continue to serve as a principle source of energy for industries and daily life. However, their release into the environment is a worldwide concern since some products are acutely toxic or possess mutagenic, teratogenic and carcinogenic properties. Several oil disposal methods have been applied over time with remediation emerging as the most promising technology. It takes advantage of the versatility of soil microbes to degrade hydrocarbon contaminants. Unlike conventional disposal methods, bioremediation ids an environmentally friendly and cost effective method that stimulate natural processes for complete degradation of hydrocarbons into innocuous compounds. This study focused on isolation, morphological and biochemical characterization of bacteria possessing hydrocarbon degrading properties. The study also aimed at optimizing appropriate culture conditions for the isolates. Isolation of hydrocarbon degrading bacteria from soils polluted with crude oil in Elebel, Emeyal I, Emeyal II in Ogbia, Bayelsa State was carried out using mineral salt medium supplemented with 1% crude oil, and the isolates were screened on their ability to use carbon as their sole source of carbon or alternative pathway. Characterization of the isolates was carried out by performing Gram’s iodine test, catalase, oxidase, indole, citrate, motility, coagulase tests. The degrading potential of the isolates were obtained by subculturing them in mineral salt medium for two weeks at room temperature, organisms that could utilize all crude oil made available to them were considered strong degraders while those that could not utilize all the crude oil made available to them were considered weak degraders. Among 40 microbes isolated, 30 were considered strong degraders while 10 were considered weak degraders and these isolates includedPseudomonasspp,Enterobacterspp,Escherichia coli,Arthrobacterspp,Bacillusspp,Acinetobacterspp,Staphylococcus aureus, coagulase negativeStaphylococcusspp,Klebsiellaspp,Micrococcusspp,Vibriospp. The characterized isolates may constitute potential candidates for biotechnological application in environmental cleanup of petroleum contaminants.
Identification and neuroprotective properties of NA-184, a selective calpain-2 inhibitor
Authors: Baudry Michel , Wang Yubin , Bi Xiaoning , Luo Yun Lyna , Wang Zhijun , Kamal Zeechan , Shirokov Alexander , Sullivan Ed , Lagasca Dennis , Khalil Hany , Lee Gary , Fosnaugh Kathy , Bey Philippe , Medi Shujaath , Coulter Greg 
Published: October 2023

AbstractOur laboratory has shown that calpain-2 activation in the brain following acute injury is directly related to neuronal damage and the long-term functional consequences of the injury, while calpain-1 activation is generally neuroprotective and calpain-1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain-2 inhibitor, referred to as C2I, enhanced long-term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Similar results were also obtained in conditional calpain-2 knock-out mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we report here the discovery of a selective calpain-2 inhibitor NA-184, (S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide whose properties make it a good clinical candidate for the treatment of TBI.
Sibling chimerism among microglia in marmosets
Authors: Rosario Ricardo C.H. del , Krienen Fenna M. , Zhang Qiangge , Goldman Melissa , Mello Curtis , Lutservitz Alyssa , Ichihara Kiku , Wysoker Alec , Nemesh James , Feng Guoping , McCarroll Steven A. 
Published: October 2023

AbstractChimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in whichin uteroconnected circulatory systems (through which stem cells transit) lead to persistent blood chimerism (12-80%) throughout life. The presence of Y-chromosome DNA sequences in other organs of female marmosets has long suggested that chimerism might also affect these organs. However, a longstanding question is whether this chimerism is driven by blood-derived cells or involves contributions from other cell types. To address this question, we analyzed single-cell RNA-seq data from blood, liver, kidney and multiple brain regions across a number of marmosets, using transcribed single nucleotide polymorphisms (SNPs) to identify cells with the sibling’s genome in various cell types within these tissues. Sibling-derived chimerism in all tissues arose entirely from cells of hematopoietic origin (i.e., myeloid and lymphoid lineages). In brain tissue this was reflected as sibling-derived chimerism among microglia (20-52%) and macrophages (18-64%) but not among other resident cell types (i.e., neurons, glia or ependymal cells). The percentage of microglia that were sibling-derived showed significant variation across brain regions, even within individual animals, likely reflecting distinct responses by siblings’ microglia to local recruitment or proliferation cues or, potentially, distinct clonal expansion histories in different brain areas. In the animals and tissues we analyzed, microglial gene expression profiles bore a much stronger relationship to local/host context than to sibling genetic differences. Naturally occurring marmoset chimerism will provide new ways to understand the effects of genes, mutations and brain contexts on microglial biology and to distinguish between effects of microglia and other cell types on brain phenotypes.
High-throughput single-cell sorting by stimulated Raman-activated cell ejection
Authors: Zhang Jing , Lin Haonan , Xu Jiabao , Zhang Meng , Ge Xiaowei , Zhang Chi , Huang Wei E. , Cheng Ji-Xin 
Published: October 2023

AbstractSingle-cell sorting is essential to explore cellular heterogeneity in biology and medicine. Recently developed Raman-activated cell sorting (RACS) circumvents the limitations of fluorescence-activated cell sorting, such as the cytotoxicity of labels. However, the sorting throughputs of all forms of RACS are limited by the intrinsically small cross-section of spontaneous Raman scattering. Here, we report a stimulated Raman-activated cell ejection (S-RACE) platform that enables high-throughput single-cell sorting based on high-resolution multi-channel stimulated Raman chemical imaging,in situimage decomposition, and laser-induced cell ejection. The performance of this platform was illustrated by sorting a mixture of 1 μm polymer beads, where 95% yield, 98% purity, and 14 events per second throughput were achieved. Notably, our platform allows live cell ejection, allowing for the growth of single colonies of bacteria and fungi after sorting. To further illustrate the chemical selectivity, lipid-richRhodotorula glutiniscells were successfully sorted from a mixture withSaccharomyces cerevisiae, confirmed by downstream quantitative PCR. Furthermore, by integrating a closed-loop feedback control circuit into the system, we realized real-time single-cell imaging and sorting, and applied this method to precisely eject regions of interest from a rat brain tissue section. The reported S-RACE platform opens exciting opportunities for a wide range of single-cell applications in biology and medicine.Significance statementImage-guided single-cell sorting is a potent tool in diverse biological applications. Current microfluidic cell sorting methods encounter challenges in handling smaller cells and are not applicable to tissue sections. To address these challenges, we have developed a stimulated Raman-activated cell ejection (S-RACE) platform, which is the first demonstration of single-cell ejection coupled with coherent Raman scattering. S-RACE allows label-free chemical imaging guided cell sorting through multispectral stimulated Raman scattering (SRS) imaging, on-the-fly image analysis, and laser-induced cell ejection. Versatile applications of S-RACE to a wide range of samples, such as polymer particles, single-live bacteria, single-live fungus, and tissue sections, are demonstrated.
Tactile versus Motor Imagery: Differences in Corticospinal Excitability Assessed with single-pulse TMS
Authors: Morozova Marina , Nasibullina Aigul , Yakovlev Lev , Syrov Nikolay , Kaplan Alexander , Lebedev Mikhail 
Published: October 2023

AbstractTactile Imagery (TI) remains a fairly understudied phenomenon despite an increased attention to this topic in recent years. Here we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for the development of imagery-based and TS-based brain-computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plastic changes in sensorimotor circuitry.Significance StatementWhile it is known that tactile imagery (TI) engages the primary somatosensory cortex similarly to physical tactile perceptions, it is not well understood how TI affects neural processing in the primary motor cortex (M1), the area that controls voluntary movements while receiving somatosensory feedback. This study employed transcranial magnetic stimulation (TMS) to examine the responsiveness of M1 to different types of somatosensory imagery in response to TMS. TI facilitated the responses in the forearm and hand muscles but to a significantly lesser extent compared to kinesthetic motor imagery (kMI). This demonstration of the distinct effects of TI and kMI on corticospinal excitability highlights the importance of selecting an imagery strategy when using imagery to modulate cortical representation of the body. These findings have practical implications for the development of imagery-based brain-computer interfaces (BCIs) intended for rehabilitation of sensorimotor impairments.
Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxiety
Authors: Riga Danai , Rademakers Kelly , Wolterink-Donselaar Inge G. , Meye Frank J. 
Published: October 2023

Abstract / SummaryAdaptive responses to challenging environments depend on optimal function of the locus coeruleus (LC), the brain’s main source of noradrenaline and primary mediator of the initial stress response. Built-in systems that exert regulatory control over the LC are largely unidentified. A good candidate system is neuropeptide Y (NPY), which is traditionally linked to anxiety-relief. Currently, the endogenous source of NPY to the LC, and how NPY-expressing neurons modulate the noradrenergic system to regulate anxiety remain unclear. We here identify, in mice, a novel NPY-expressing neuronal population (peri-LCNPY) neighboring LC noradrenergic neurons that locally innervates the pericoerulean space. Moreover, we demonstrate that stress engages peri-LCNPYneurons, increasing their excitability. Mimicking peri-LCNPYneuronal activation usingex vivochemogenetics suppresses LC noradrenergic neuron activity, via an NPY Y1 receptor-mediated mechanism. Furthermore,in vivochemogenetic stimulation of peri-LCNPYneurons results in Y1R-dependent anxiety-relief. Conversely, inhibiting peri-LCNPYneurons increases anxiety-like behaviors. Together, we establish a causal role for peri-LCNPY-mediated neuromodulation of the LC in the regulation of anxiety, providing novel insights in the endogenous mechanisms underlying adaptive responses to adversity.