bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal denoising through topographic modularity of neural circuits
Authors: Zajzon Barna , Dahmen David , Morrison Abigail , Duarte Renato 
Published: January 2022

AbstractInformation from the sensory periphery is conveyed to the cortex via structured projection pathways that spatially segregate stimulus features, providing a robust and efficient encoding strategy. Beyond sensory encoding, this prominent anatomical feature extends throughout the neocortex. However, the extent to which it influences cortical processing is unclear. In this study, we combine cortical circuit modeling with network theory to demonstrate that the sharpness of topographic projections acts as a bifurcation parameter, controlling the macroscopic dynamics and representational precision across a modular network. By shifting the balance of excitation and inhibition, topographic modularity gradually increases task performance and improves the signal-to-noise ratio across the system. We demonstrate that in biologically constrained networks, such a denoising behavior is contingent on recurrent inhibition. We show that this is a robust and generic structural feature that enables a broad range of behaviorally-relevant operating regimes, and provide an in-depth theoretical analysis unravelling the dynamical principles underlying the mechanism.
Spinal cord homeostatic plasticity gates mechanical allodynia in chronic pain
Authors: Cao Bing , Scherrer Gregory , Chen Lu 
Published: January 2022

SUMMARYCentral sensitization caused by disinhibition of spinal cord circuits is a key mechanism of mechanical allodynia in neuropathic pain. Despite intense efforts, the molecular mechanisms that drive disinhibition and induce allodynia after peripheral nerve injury remain unclear. Using the spared-nerve injury (SNI) model of allodynia, we here demonstrate that SNI induces disinhibition of spinal nociceptive circuits by triggering homeostatic synaptic plasticity. Specifically, SNI-triggered homeostatic plasticity suppresses the inhibitory outputs of parvalbumin-positive (PV+) interneurons that form synapses on both primary afferent terminals and excitatory interneurons, causing hyperactivation of the nociceptive pathway. Using genetic manipulations, we identified the retinoic acid receptor RARα as the key mediator of the homeostatic synaptic plasticity underlying this synaptic disinhibition. Deletion of RARα in PV+ neurons blocked SNI-induced spinal disinhibition, central sensitization, and allodynia. Moreover, deletion of RARα in spinal PV+ neurons or application of an RARα antagonist in the spinal cord prevented the development of SNI-induced mechanical allodynia. Together, our results reveal a molecular mechanism of neuropathic pain whereby homeostatic plasticity causes the mis-direction of tactile information flow to ascending nociceptive pathways following peripheral nerve injury.
Corrective feedback control of competing neural network with entire connections
Authors: Wang Uramogi 
Published: January 2022

AbstractContinuous persist activity of the competitive network is related to many functions, such as working memory, oculomotor integrator and decision making. Many competition models with mutual inhibition structures achieve activity maintenance via positive feedback, which requires meticulous fine tuning of the network parameters strictly. Negative derivative feedback, according to recent research, might represent a novel mechanism for sustaining neural activity that is more resistant to multiple neural perturbations than positive feedback. Many classic models with only mutual inhibition structure are not capable of providing negative derivative feedback because double-inhibition acts as a positive feedback loop, and lack of negative feedback loop that is indispensable for negative derivative feedback. Here in the proposal, we aim to derive a new competition network with negative derivative feedback. The network is made up of two symmetric pairs of EI populations that the four population are completely connected. We conclude that the negative derivative occurs in two circumstances, in which one the activity of the two sides is synchronous but push-pull-like in the other, as well as the switch of two conditions in mathematical analysis and numerical simulation.
Systemic infection of SARS-CoV-2 in free ranging Leopard (Panthera pardus fusca) in India
Authors: Mahajan Sonalika , Karikalan Mathesh , Chander Vishal , Pawde Abhijit M. , Saikumar G , Semmaran M , Lakshmi P Sree , Sharma Megha , Nandi Sukdeb , Singh Karam Pal , Gupta Vivek Kumar , Singh Raj Kumar , Sharma Gaurav Kumar 
Published: January 2022

AbstractWe report patho-morphological and virological characterization of SARS-CoV-2 in naturally infected, free ranging Indian Leopard (Panthera pardus fusca). Whole genome sequence analysis confirmed infection of Delta variant of SARS-CoV-2, possibly spill over from humans, but the case was detected when infection level had dropped significantly in human population. This report underlines the need for intensive screening of wild animals for keeping track of the virus evolution and development of carrier status of SARS-CoV-2 among wildlife species.
40 new specimens ofIchthyornisprovide unprecedented insight into the postcranial morphology of crownward stem group birds
Authors: Benito Juan , Chen Albert , Wilson Laura E. , Bhullar Bhart-Anjan S. , Burnham David , Field Daniel J. 
Published: January 2022

ABSTRACTIchthyornishas long been recognized as a pivotally important fossil taxon for understanding the latest stages of the dinosaur–bird transition, but little significant new postcranial material has been brought to light since initial descriptions of partial skeletons in the 19thCentury. Here, we present new information on the postcranial morphology ofIchthyornisfrom 40 previously undescribed specimens, providing the most detailed morphological assessment ofIchthyornisto date. The new material includes four partially complete skeletons and numerous well-preserved isolated elements, enabling new anatomical observations such as muscle attachments previously undescribed for Mesozoic euornitheans. Among the elements that were previously unknown or poorly represented forIchthyornis, the new specimens include an almost-complete axial series, a hypocleideum-bearing furcula, radial carpal bones, fibulae, a complete tarsometatarsus bearing a rudimentary hypotarsus, and one of the first-known nearly complete three-dimensional sterna from a Mesozoic avialan. Several pedal phalanges are preserved, revealing a remarkably enlarged pes presumably related to foot-propelled swimming. Although diagnosable asIchthyornis, the new specimens exhibit a substantial degree of morphological variation, some of which may relate to ontogenetic changes. Phylogenetic analyses incorporating our new data and employing alternative morphological datasets recoverIchthyornisstemward of Hesperornithes andIaceornis, in line with some recent hypotheses regarding the topology of the crownward-most portion of the avian stem group, and we establish phylogenetically-defined clade names for relevant avialan subclades to help facilitate consistent discourse in future work. The new information provided by these specimens improves our understanding of morphological evolution among the crownward-most non-neornithine avialans immediately preceding the origin of crown group birds.
Divergence and introgression among the virilis group of Drosophila
Authors: Yusuf Leeban H. , Tyukmaeva Venera , Hoikkala Anneli , Ritchie Michael G. 
Published: January 2022

AbstractSpeciation with gene flow is now widely regarded as common. However, the frequency of introgression between recently diverged species and the evolutionary consequences of gene flow are still poorly understood. The virilis group of Drosophila contains around a dozen species that are geographically widespread and show varying levels of pre-zygotic and post-zygotic isolation. Here, we utilize de novo genome assemblies and whole-genome sequencing data to resolve phylogenetic relationships and describe patterns of introgression and divergence across the group. We suggest that the virilis group consists of three, rather than the traditional two, subgroups. We found evidence of pervasive phylogenetic discordance caused by ancient introgression events between distant lineages within the group, and much more recent gene flow between closely-related species. When assessing patterns of genome-wide divergence in species pairs across the group, we found no consistent genomic evidence of a disproportionate role for the X chromosome. Some genes undergoing rapid sequence divergence across the group were involved in chemical communication and may be related to the evolution of sexual isolation. We suggest that gene flow between closely-related species has potentially had an impact on lineage-specific adaptation and the evolution of reproductive barriers. Our results show how ancient and recent introgression confuse phylogenetic reconstruction, and suggest that shared variation can facilitate adaptation and speciation.
House sparrows do not exhibit a preference for the scent of potential partners with different MHC-I allele numbers and genetic distances
Authors: Amo Luisa , de Paz Guillermo Amo , Kabbert Johanna , Machordom Annie 
Published: January 2022

AbstractMHC genes play a fundamental role in immune recognition of pathogens and parasites. Therefore, females may increase offspring heterozygosity and genetic diversity by selecting MHC genetically compatible or heterozygous males. In birds, several studies suggest that MHC genes play a role in mate choice, and recent evidence suggest that olfaction may play a role in such discrimination. Previous studies indicated that house sparrow females with low allelic diversity prefer males with higher diversity in MHC-I alleles. Here, we directly explored whether both house sparrow females and males could estimate by scent the number in MHC amino acid and functional variants as well as the level of MHC-I similarity or dissimilarity of potential partners. Our results show that neither females nor males exhibit a preference related to the number of MHC-I amino acid variants or functional variants or in relation to MHC amino acid or functional similarity of potential partners, suggesting that MHC-I is not detected through olfaction. Further studies are needed to understand the mechanisms responsible for MHC-I based mate discrimination in birds.
High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake in young men independently of changes in thermogenesis and the gut microbiome
Authors: Richard Gabriel , Blondin Denis P. , Syed Saad A. , Rossi Laura , Fontes Michelle E. , Fortin Mélanie , Phoenix Serge , Frisch Frédérique , Dubreuil Stéphanie , Guérin Brigitte , Turcotte Éric E. , Lepage Martin , Surette Michael G. , Schertzer Jonathan D. , Steinberg Gregory R. , Morrison Katherine M. , Carpentier André C. 
Published: January 2022

SummaryDiets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with insulin resistance and dyslipidemia during fructose overconsumption in humans.
Identification of Mfn2-S249 as a Phosphoregulatory Switch of Mitochondrial Fusion Dynamics
Authors: Kumar Sanjay , Ramonett Aaron , Ahmed Tasmia , Kwak Eun-A , Flores Paola Cruz , Ortiz Hannah R. , Langlais Paul R. , Mythreye Karthikeyan , Lee Nam Y. 
Published: January 2022

SUMMARYMitochondrial remodeling is a fundamental process underlying cellular respiration and metabolism. Here we report TAK1 as a direct regulator of mitochondrial fusion. TAK1 is activated by a variety of mitogenic factors, cytokines and environmental stimuli, which we find induces rapid fragmentation through Mfn2 inactivation. TAK1 phosphorylates Mfn2 at Ser249, which inhibits the binding of GTP required for Mfn trans-dimerization and mitochondrial membrane fusion. Accordingly, expression of Mfn2-S249 phosphomimetics (Mfn2-E/D) constitutively promote fission whereas alanine mutant (Mfn2-A) yields hyperfused mitochondria and increased bioenergetics in cells. In mice, Mfn2-E knock-in yields embryonic lethality in homozygotes whereas heterozygotes are viable but exhibit increased visceral fat accumulation despite normal body weight and cognitive/motor functions compared to wildtype and Mfn2-A mice. Mature white adipocytes isolated from mutant mice reveal cell-autonomous TAK1-related effects on mitochondrial remodeling and lipid metabolism. These results identify Mfn2-S249 as a dynamic phosphoregulatory switch of mitochondrial fusion during development and energy homeostasis.
Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2
Authors: Unal Mehnmet Altay , Besbinar Omur , Nazir Hasan , Summak Gokce Yagmur , Bayrakdar Fatma , Delogu Lucia Gemma , Taskin Tambay , Ozkan Sibel Aysil , Akcali Kamil Can , Yilmazer Acelya 
Published: January 2022

AbstractSince the first cases the coronavirus disease caused by SARS-CoV-2 (COVID-19) reported in December 2019, worldwide continuous efforts have been placed both for the prevention and treatment of this infectious disease. As new variants of the virus emerge, the need for an effective antiviral treatment continues. The concept of preventing SARS-CoV-2 on both pre-entry and post-entry stages has not been much studied. Therefore, we compared the antiviral activities of three antiviral drugs which have been currently used in the clinic. In silico docking analyses and in vitro viral infection in Vero E6 cells were performed to delineate their antiviral effectivity when used alone or in combination. Both in silico and in vitro results suggest that the combinatorial treatment by favipiravir and umifenovir or camostat mesylate has more antiviral activity against SARS-CoV-2 rather than single drug treatment. These results suggest that inhibiting both viral entry and viral replication at the same time is much more effective for the antiviral treatment of SARS-CoV-2.
Background selection from unlinked sites causes non-independent evolution of deleterious mutations
Authors: Matheson Joseph , Masel Joanna 
Published: January 2022

ABSTRACTBackground selection describes the reduction in neutral diversity caused by selection against deleterious alleles at other loci. It is typically assumed that the purging of deleterious alleles affects linked neutral variants, and indeed simulations typically only treat a genomic window. However, background selection at unlinked loci also depresses neutral diversity. In agreement with previous analytical approximations, in our simulations of a human-like genome with a realistically high genome-wide deleterious mutation rate, the effects of unlinked background selection exceed those of linked background selection. Background selection reduces neutral genetic diversity by a factor that is independent of census population size. Outside of genic regions, the strength of background selection increases with the mean selection coefficient, contradicting the linked theory but in agreement with the unlinked theory. Neutral diversity within genic regions is fairly independent of the strength of selection. Deleterious genetic load among haploid individuals is underdispersed, indicating non-independent evolution of deleterious mutations. Empirical evidence for underdispersion was previously interpreted as evidence for global epistasis, but we recover it from a non-epistatic model.SIGNIFICANCEAs individuals bearing deleterious alleles are removed from a population, other alleles are removed with them, some that are tightly linked near the deleterious allele on a chromosome and some that aren’t linked at all. When the deleterious mutation rate is realistically high, unlinked pairs of loci are a more important influence on the removal of genetic variation. Simulations that assume independent evolution cannot capture removal just by using a lower “effective population size”, because the probabilities of having deleterious alleles on different chromosomes are negatively correlated rather than independent.
A framework for the quantification of soundscape diversity using Hill numbers
Authors: Luypaert Thomas , Bueno Anderson S. , Masseli Gabriel S. , Kaefer Igor L. , Campos-Cerqueira Marconi , Peres Carlos A. , Haugaasen Torbjørn 
Published: January 2022

AbstractSoundscape studies are increasingly common to capture landscape-scale ecological patterns. Yet, several aspects of soundscape diversity quantification remain unexplored. Although some processes influencing acoustic niche usage may operate in the 24h domain, most acoustic indices only capture the diversity of sounds co-occurring in sound files at a specific time of day. Moreover, many indices do not consider the relationship between the spectral and temporal traits of sounds simultaneously. To provide novel insights into landscape-scale patterns of acoustic niche usage at broader temporal scales, we present a workflow to quantify soundscape diversity through the lens of functional ecology.Our workflow quantifies the functional diversity of sound in the 24-hour acoustic trait space. We put forward an entity, the Operational Sound Unit (OSU), which groups sounds by their shared functional properties. Using OSUs as our unit of diversity measurement, and building on the framework of Hill numbers, we propose three metrics that capture different aspects of acoustic trait space usage: (i) soundscape richness; (ii) soundscape diversity; (iii) soundscape evenness. We demonstrate the use of these metrics by (a) simulating soundscapes to assess if the indices possess a set of desirable behaviours; and (b) quantifying the soundscape richness and evenness along a gradient in species richness to illustrate how these metrics can be used to shed unique insights into patterns of acoustic niche usage.We demonstrate that: (a) the indices outlined herein have desirable behaviours; and (b) the soundscape richness and evenness are positively correlated with the richness of soniferous species. This suggests that the acoustic niche space is more filled where taxonomic richness is higher. Moreover, species-poor acoustic communities have a higher proportion of rare sounds and use the acoustic space less effectively. As the correlation between the soundscape and taxonomic richness is strong (>0.8) and holds at low sampling intensities, soundscape richness could serve as a proxy for taxonomic richness.Quantifying the soundscape diversity through the lens of functional ecology using the analytical framework of Hill numbers generates novel insights into acoustic niche usage at a landscape scale and provides a useful proxy for taxonomic richness measurement.
A host–gut microbial co-metabolite of aromatic amino acids, p-cresol glucuronide, promotes blood–brain barrier integrity in vivo
Authors: Stachulski Andrew V. , Knausenberger Tobias B-A , Shah Sita N. , Hoyles Lesley , McArthur Simon 
Published: January 2022

AbstractPurposeThe sequential activity of gut microbial and host processes can exert a powerful modulatory influence on dietary components, as exemplified by the metabolism of the amino acids tyrosine and phenylalanine to p-cresol by gut microbes, and then to p-cresol glucuronide (pCG) by host enzymes. Although such glucuronide conjugates are classically thought to be biologically inert, there is accumulating evidence that this may not always be the case. We investigated the activity of pCG, studying its interactions with the cerebral vasculature and the brain in vitro and in vivo.MethodsMale C57Bl/6J mice were used to assess blood–brain barrier (BBB) permeability and whole brain transcriptomic changes in response to pCG treatment. Effects were then further explored using the human cerebromicrovascular endothelial cell line hCMEC/D3, assessing paracellular permeability, transendothelial electrical resistance and barrier protein expression.ResultsMice exposed to pCG showed reduced BBB permeability and significant changes in whole brain transcriptome expression. Surprisingly, treatment of hCMEC/D3 cells with pCG had no notable effects until co-administered with bacterial lipopolysaccharide, at which point it was able to prevent the permeabilising effects of endotoxin. Further analysis suggested that pCG acts as an antagonist at the principal lipopolysaccharide receptor TLR4.ConclusionThe amino acid phase II metabolic product pCG is biologically active at the BBB, highlighting the complexity of gut microbe to host communication and the gut–brain axis.
Vitamin C functions as double-edge sword on cancer progression depending on ERK activation or inhibition mediated by its receptor SVCT2
Authors: Guan Yian , Chen Bingxue , Wu Yongyan , Han Zhuo , Xu Hongyu , Zhang Caixia , Hao Weijie , Gao Wei , Guo Zekun 
Published: January 2022

AbstractThe effect of Vitamin C (Vc) in oncotherapy was controversial for decades. And hyperactivation of extracellular signal-regulated kinase (ERK) drove tumorigenesis. Herein, we demonstrated that Vc activated ERK through sodium-dependent Vc transporter 2 (SVCT2), while high-dose Vc resulted in persistent ERK feedback inhibition following activation. Extracellular Vc binding to SVCT2 initiated ERK activation, then transmembrane transport of Vc induced dimerization of SVCT2. Activated ERK phosphorylated protein tyrosine phosphatase non-receptor type 12 (PTPN12) at Ser434and inhibited PTPN12 activity, thus enhancing phosphorylation of Janus kinase 2 (JAK2), which phosphorylated growth factor receptor bound protein 2 (GRB2) at Tyr160to promote GRB2 dimers dissociation and recruitment of GRB2 to SVCT2, leading to further ERK activation. Different cancers have different sensitivities to Vc, the dose effects of Vc on cancer phenotypes depended on that ERK was activated or inhibited. These findings suggest SVCT2 is a Vc receptor mediating the ERK-PTPN12-JAK2-GRB2-ERK positive feedback loop and a potential target for oncotherapy.Abstract graphic