bluuebunny/crossref_metadata_2025_split huggingface dataset:
Felidae call type and species identification based on acoustic features
Authors: Bandara Danushka , Exantus Karen , Navarro-Martinez Cristian , Patterson Murray , Byun Ashley 
Published: April 2022

ABSTRACTThe cat family Felidae is one of the most successful carnivore lineages today. However, the study of the evolution of acoustic communication between felids remains a challenge due to the lack of fossils, the limited availability of audio recordings because of their largely solitary and secretive behavior, and the underdevelopment of computational models and methods needed to address acoustic evolutionary questions. This study is a first attempt at developing a machine learning-based approach to the classification of felid calls as well as the identification of acoustic features that distinguish felid call types and species from one another. A felid call dataset was developed by extracting audio clips from diverse sources. The audio clips were manually annotated for call type and species. Due to the limited availability of samples, this study focused on the Pantherinae subfamily. Time-frequency features were then extracted from the Pantherinae dataset. Finally, several classification algorithms were applied to the resulting data. We achieved 91% accuracy for this Pantherinae call type classification. For the species classification, we obtained 86% accuracy. We also obtained the most predictive features for each of the classifications performed. These features can inform future research into the evolutionary acoustic analysis of the felid group.
Fear extinction is regulated by long noncoding RNA activity at the synapse
Authors: Liau Wei-Siang , Zhao Qiongyi , Bademosi Adekunle , Gormal Rachel , Gong Hao , Marshall Paul R. , Periyakaruppiah Ambika , Madugalle Sachithrani U. , Zajackowski Esmi L. , Leighton Laura J. , Ren Haobin , Musgrove Mason , Davies Joshua , Rauch Simone , He Chuan , Dickinson Bryan C. , Li Xiang , Wei Wei , Meunier Frédéric A. , Fernandez Moya Sandra M. , Kiebler Michael A. , Srinivasan Bharath , Banerjee Sourav , Clark Michael , Spitale Robert C. , Bredy Timothy W. 
Published: April 2022

SummaryLong noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are expressed at the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq on synaptosomes, we identified a significant number of lncRNAs that accumulate at synapses within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these is a splice variant related to the stress-associated lncRNA, Gas5. RNA immunoprecipitation followed by mass spectrometry and single molecule imaging revealed that this Gas5 isoform, in association with the RNA binding proteins G3bp2 and Caprin1, regulates the activity-dependent trafficking and clustering of RNA granules in dendrites. In addition, we found that cell-type-specific, state-dependent, and synapse-specific knockdown of the Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and the coordination of RNA condensates in the synaptic compartment.
Atypical Child-Parent Neural Synchrony Links to Children’s Psychopathological Symptoms
Authors: Su Haowen , Young Christina B. , Han Zhuo Rachel , Xu Jianjie , Xiong Bingsen , Wang Jingyi , Hao Lei , Yang Zhi , Chen Gang , Qin Shaozheng 
Published: April 2022

AbstractFamily emotional climate is fundamental to child’s emotional wellbeing and mental health. Negative family emotional climate may lead to heightened psychopathological symptoms via dysfunctional child-parent interactions. Single-brain paradigms have uncovered changes in brain systems and networks related to negative family environments, but how neurobiological reciprocity between child and parent brains is associated with children’s psychopathological symptoms remains unknown. In study1, we investigated the relationship between family emotional climate and children’s psychopathological symptoms in 395 child-parent dyads. In study2, using a naturalistic movie-watching functional magnetic imaging technique in a subsample of 100 children and parents, we investigate the neurobiological underpinnings of how family emotional climate is associated with children’s psychopathological symptoms through child-parent neural synchrony. Children from negative family emotional climate experienced more severe psychopathological symptoms. We revealed significantly higher inter-subject correlations in the dorsal and ventral portions of the medial prefrontal cortex (mPFC), and greater concordance of activity with widespread brain regions critical for socioemotional skills in child-parent than child-stranger dyads. Critically, negative family emotional climate was associated with decreased inter-subject functional correlation between the ventral mPFC and the hippocampus in child-parent dyads, which further accounted for higher children’s internalizing symptoms especially for anxious and depressed aspects. Family emotional climate might transmit into the brain of parent-child dyads, which may associate with child development outcomes. The present study identified that child-parent vmPFC-hippocampal circuitry is linked to children’s psychopathological symptoms. Our findings suggest a neurobiological mechanism of how negative family emotional climate affects children’s psychopathological symptoms through altered child-parent neural synchrony.
Identification of C270 as a novel site for allosteric modulators of SARS-CoV-2 papain-like protease
Authors: Hu Hangchen , Wang Qian , Su Haixia , Shao Qiang , Zhao Wenfeng , Chen Guofeng , Li Minjun , Xu Yechun 
Published: April 2022

AbstractThe papain-like protease (PLpro) in coronavirus is one of key cysteine proteases responsible for the proteolytic processing of viral polyproteins, and plays an important role in dysregulation of host immune response. PLprois a promising therapeutic target with a major challenge in inhibitor design due to the restricted S1/S2 sites for two consecutive glycine of substrates. Here we reported the discovery of two activators of the SARS-CoV-2 PLprofrom a biochemical screening, and the identification of the unique residue, C270, as an allosteric and covalent regulation site for the activators. This site was also specifically modified by glutathione oxidized, resulting in the S-glutathionylation and activation of the protease. Furthermore, one compound was found to allosterically inhibit the protease by covalent binding to this crucial site. Together, these results elucidated an unrevealed molecular mechanism for allosteric modulation of the protease’s activity, and provided a new strategy for discovery of allosteric inhibitors of the SARS-CoV-2 PLpro.
Identification and characterization of the T cell receptor (TCR) repertoire of the Cynomolgus macaque (Macaca Fascicularis)
Authors: Jaiswal Swati , Boyce Shayla , Nyquist Sarah K. , Jivanjee Tasneem , Ibrahim Samira , Bromley Joshua D. , Gatter G. James , Gideon Hannah P. , Patel Kush V. , Ganchua Sharie Keanne C. , Berger Bonnie , Fortune Sarah M. , Flynn JoAnne L. , Shalek Alex K. , Behar Samuel M. 
Published: April 2022

AbstractBackgroundNon-human primates (NHP) are desirable as animal models of human disease because they share behavioral, physiological, and genomic traits with people. Hence, NHP recapitulate manifestations of disease not observed in other animal species. The Macaca fascicularis (i.e., Cynomolgus macaque) is an NHP species extensively used for biomedical research, but the TCR repertoire hasn’t been characterized yet.ResultWe used the genomic sequences to design primers to identify the expressed TCR repertoire by single cell RNAseq. The data analysis from 22 unique samples were used to assign a functional status to each TCR genes. We identified and analyzed the TRA/D, TRB and TRG loci of the Cynomolgus macaque.ConclusionThe genomic organization of the Cynomolgus macaque has great similarity with Macaca mulatta (i.e., Rhesus macaque) and they shared >90% sequence similarity with the human TCR repertoire. These data will facilitate the analysis of T cell immunity in Cynomolgus macaques.
High-contrast en-bloc staining of mouse whole-brain samples for EM-based connectomics
Authors: Song Kun , Feng Zhihui , Helmstaedter Moritz 
Published: April 2022

ABSTRACTConnectomes of human cortical gray matter require high-contrast homogeneously stained samples sized at least 2-3 mm on a side, and a whole-mouse brain connectome requires samples sized at least 5-10 mm on a side. Here we report en-bloc staining and embedding protocols for these and other applications, removing a key obstacle for connectomic analyses at mammalian whole-brain level.
The Role of Replication-induced Chromosomal Copy Numbers in Spatio-temporal Gene Regulation and Evolutionary Chromosome Plasticity
Authors: Teufel Marc , Henkel Werner , Sobetzko Patrick 
Published: April 2022

ABSTRACTFor a coherent response to environmental changes, bacterial evolution has formed a complex transcriptional regulatory system comprising classical DNA binding proteins sigma factors and modulation of DNA topology. In this study, we investigate replication-induced gene copy numbers - a regulatory concept that is unlike the others not based on modulation of promoter activity but replication dynamics. We show that a large fraction of genes are predominantly affected by transient copy numbers and identify cellular functions and central pathways governed by this mechanism in Escherichia coli. Furthermore, we show quantitatively that the previously observed spatio-temporal expression pattern between different growth phases mainly emerges from transient chromosomal copy numbers. We extend the analysis to the plant pathogen Dickeya dadantii and the biotechnologically relevant organism Vibrio natriegens. The analysis reveals a connection between growth phase dependent gene expression and evolutionary gene migration in these species. Further extension to the bacterial kingdom shows that chromosome evolution is governed by growth rate related transient copy numbers.
Deep learning to decompose macromolecules into independent Markovian domains
Authors: Mardt Andreas , Hempel Tim , Clementi Cecilia , Noé Frank 
Published: April 2022

AbstractThe increasing interest in modeling the dynamics of ever larger proteins has revealed a fundamental problem with models that describe the molecular system as being in a global configuration state. This notion limits our ability to gather sufficient statistics of state probabilities or state-to-state transitions because for large molecular systems the number of metastable states grows exponentially with size. In this manuscript, we approach this challenge by introducing a method that combines our recent progress on independent Markov decomposition (IMD) with VAMPnets, a deep learning approach to Markov modeling. We establish a training objective that quantifies how well a given decomposition of the molecular system into independent subdomains with Markovian dynamics approximates the overall dynamics. By constructing an end-to-end learning framework, the decomposition into such subdomains and their individual Markov state models are simultaneously learned, providing a data-efficient and easily interpretable summary of the complex system dynamics. While learning the dynamical coupling between Markovian subdomains is still an open issue, the present results are a significant step towards learning “Ising models” of large molecular complexes from simulation data.
Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells
Authors: Mäki-Marttunen Tuomo , Mäki-Marttunen Verónica 
Published: April 2022

AbstractDendrites of cortical pyramidal cells are densely populated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, a.k.a. Ih channels. Ih channels are targeted by multiple neuromodulatory pathways, and thus are one of the key ion-channel populations regulating the pyramidal cell activity. Previous observations and theories attribute opposing effects of the Ih channels on neuronal excitability due to their mildly hyperpolarized reversal potential. These effects are difficult to measure experimentally due to the fine spatiotemporal landscape of the Ih activity in the dendrites, but computational models provide an efficient tool for studying this question in a reduced but generalizable setting. In this work, we build upon existing biophysically detailed models of thick-tufted layer V pyramidal cells and model the effects of over- and under-expression of Ih channels as well as their neuromodulation by dopamine (gain of Ih function) and acetylcholine (loss of Ih function). We show that Ih channels facilitate the action potentials of layer V pyramidal cells in response to proximal dendritic stimulus while they hinder the action potentials in response to distal dendritic stimulus at the apical dendrite. We also show that the inhibitory action of the Ih channels in layer V pyramidal cells is due to the interactions between Ih channels and a hot zone of low voltage-activated Ca2+ channels at the apical dendrite. Our simulations suggest that a combination of Ih-enhancing neuromodulation at the proximal apical dendrite and Ih-inhibiting modulation at the distal apical dendrite can increase the layer V pyramidal excitability more than any of the two neuromodulators alone. Our analyses uncover the effects of Ih-channel neuromodulation of layer V pyramidal cells at a single-cell level and shed light on how these neurons integrate information and enable higher-order functions of the brain.
Incertohypothalamic A13 dopaminergic neurons are involved in fine forelimb movements but not reward
Authors: Garau C , Hayes J , Chiacchierini G , McCutcheon JE , Apergis-Shoute J 
Published: April 2022

AbstractTyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well-positioned to impact known dopamine-related functions since their descending projections innervate target regions that regulate vigilance, sensorimotor integration and execution. Despite this known connectivity little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects that is independent from reward. A13-DA neurons respond strongly when animals grab and manipulate food items while their inactivation or degeneration prevents animals from successfully doing so - a deficit partially attributed to a reduction in grip strength. In contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Moreover, motivation for food was unaffected as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. These results demonstrate a functional role for A13-DA neurons in prehensile actions that are uncoupled from reward and as such position A13-DA neurons into the functional framework regarding centrally-located DA populations and their ability to coordinate movement.
A divide-and-conquer approach for genomic prediction in rubber tree using machine learning
Authors: Aono Alexandre Hild , Francisco Felipe Roberto , Souza Livia Moura , Gonçalves Paulo de Souza , Scaloppi Erivaldo J. , Guen Vincent Le , Fritsche-Neto Roberto , Gorjanc Gregor , Quiles Marcos Gonçalves , de Souza Anete Pereira 
Published: April 2022

AbstractRubber tree (Hevea brasiliensis) is the main feedstock for commercial rubber; however, its long vegetative cycle has hindered the development of more productive varieties via breeding programs. With the availability ofH. brasiliensisgenomic data, several linkage maps with associated quantitative trait loci (QTLs) have been constructed and suggested as a tool for marker-assisted selection (MAS). Nonetheless, novel genomic strategies are still needed, and genomic selection (GS) may facilitate rubber tree breeding programs aimed at reducing the required cycles for performance assessment. Even though such a methodology has already been shown to be a promising tool for rubber tree breeding, increased model predictive capabilities and practical application are still needed. Here, we developed a novel machine learning-based approach for predicting rubber tree stem circumference based on molecular markers. Through a divide-and-conquer strategy, we propose a neural network prediction system with two stages: (1) subpopulation prediction and (2) phenotype estimation. This approach yielded higher accuracies than traditional statistical models in a single-environment scenario. By delivering large accuracy improvements, our methodology represents a powerful tool for use inHeveaGS strategies. Therefore, the incorporation of machine learning techniques into rubber tree GS represents an opportunity to build more robust models and optimizeHeveabreeding programs.
Introduced crops supplement rather than replace indigenous crops in an African center of agrobiodiversity
Authors: Rampersad Chris , Geto Tesfu , Samuel Tarekegn , Abebe Meseret , Gomez Marybel Soto , Pironon Samuel , Büchi Lucie , Haggar Jeremy , Stocks Jonathan , Ryan Philippa , Buggs Richard , Demissew Sebsebe , Wilkin Paul , Abebe Wendawek M. , Borrell James S. 
Published: April 2022

AbstractCrop diversity plays a major role in underpinning food security. It is especially important to smallholder and subsistence farmers, who often rely on crop diversity for stable and resilient production. Despite this, global expansion of a small pool of major crops and the associated homogenisation of global agricultural systems may decrease on-farm crop diversity.We surveyed 1,369 subsistence farms stratified across climate gradients in the Ethiopian Highlands, to characterise the richness and cultivated area of the 83 edible crops they contained. We further categorise these crops by their period of introduction to Ethiopia. We apply non-metric multidimensional scaling and mixed effects modelling to characterise agrisystem composition and test the impact of crop introductions.We find a significant positive relationship between introduced and indigenous crop richness, suggesting that crop introductions have tended to supplement rather than replace or reduce indigenous crop diversity. Geographically matched farms with higher proportions of introduced crops, had significantly higher overall crop richness. Analysis of socio-economic drivers indicates that both poverty and low accessibility are associated with reduced cultivation of modern introductions.We conclude that global patterns of major crop expansion do not necessarily result in agrobiodiversity loss for subsistence farmers, in our Ethiopian case study. Importantly, socioeconomic factors may strongly influence the farmers propensity to adopt novel species, suggesting targets for agricultural extension policies. Given the rapid climatic, economic and demographic changes impacting global food systems and the threats to food security these entail, robust indigenous agricultural systems supplemented with diverse introduced crops may enhance resilience.
Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: critical roles of CaMKIIα and MeCP2
Authors: Zhang Yili , Smolen Paul , Alberini Cristina M. , Baxter Douglas A. , Byrne John H. 
Published: April 2022

AbstractKey features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKIIα, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of bdnf, and interaction between MeCP2 and CaMKIIα, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment.Author SummaryLong-term memories (LTMs) are enduring and resistant to disruption These features are acquired via processes collectively referred to as consolidation. In adults, the initial stages of consolidation follow complex dynamics that are believed to emerge from interacting biochemical signaling pathways [1], including BDNF and CaMKIIα dependent feedback loops. Similarly, the acquisition of ability to consolidate memory in infantile animals is believed to emerge from the functional maturation of these molecular pathways [2]. Here, the ways in which these pathways contribute to consolidation were investigated using a computational model. This model provides novel explanations for the apparent rapid forgetting of infantile memory and for development of resistance to disruption during memory consolidation.