bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of pigs vocalisation structure to assess the quality of human-pig relationship
Authors: Villain Avelyne S , Guérin Carole , Tallet Céline 
Published: March 2022

AbstractStudying human-animal interactions in domestic species and how they affect the establishment of a positive Human-Animal Relationship (HAR) may help us improve animal welfare and better understand the evolution of interspecific interactions associated with the domestication process. Understanding and describing the quality of an HAR requires information on several aspects of the animal biology and emotional states (social, spatial and postural behaviours, physiological and cognitive states). Growing evidence shows that acoustic features of animal vocalisations may be indicators of emotional states. Here, we tested the hypothesis that vocal structure may indicate the quality of HAR. At weaning, 30 piglets were positively handled by an experimenter who talked to and physically interacted with them three times a day, while 30 other piglets only received the contact necessary for proper husbandry. After two weeks, we recorded the behaviours and vocalisations produced in the presence of the static experimenter for 5 min. We repeated this test two weeks later, after a conditioning period during which human presence with additional positive contacts was used as a reward for all piglets. We hypothesized this conditioning period would lead to a positive human-piglet relationship for all piglets. As expected, piglets that were positively handled at weaning expressed a higher attraction toward the experimenter, and, after the conditioning, piglets that were not positively handled at weaning expressed a similar level of attraction than the positively handled ones. Piglets positively handled at weaning produced shorter grunts than the other ones, regardless of the context of recording, which may indicate a more positive affect. During reunions with the static experimenter, a more positive HAR was associated with a decrease in vocal reactivity to human proximity. However, during reunions with the experimenter providing additional positive contacts and over the conditioning, proximity to the human systematically triggered shorter and higher pitched grunts, indicator of positive a emotional state. Results first show that changes in vocal structure are consistent with indicators of positive states in the presence of a human. Second, these changes are stronger when the human positively interact with the piglets, supposedly emphasizing a higher positive arousal state during these interactions. We show that vocalisation structure may be a promising indicator of the quality of human-pig relationship.
Case-control analysis of single-cell RNA-seq studies
Authors: Petukhov Viktor , Igolkina Anna , Rydbirk Rasmus , Mei Shenglin , Christoffersen Lars , Khodosevich Konstantin , Kharchenko Peter V. 
Published: March 2022

SummarySingle-cell RNA-seq (scRNA-seq) assays are being increasingly utilized to investigate specific hypotheses in both basic biology and clinically-applied studies. The design of most such studies can be often reduced to a comparison between two or more groups of samples, such as disease cases and healthy controls, or treatment and placebo. Comparative analysis between groups of scRNA-seq samples brings additional statistical considerations, and currently there is a lack of tools to address this common scenario. Based on our experience with comparative designs, here we present a computational suite (Cacoa – case-control analysis) to carry out statistical tests, exploration, and visualization of scRNA-seq sample cohorts. Using multiple example datasets, we demonstrate how application of these techniques can provide additional insights, and avoid issues stemming from inter-individual variability, limited sample size, and high dimensionality of the data.
Genomics epidemiology analysis reveals hidden signatures of drug resistance in Mycobacterium tuberculosis
Authors: Mejía-Ponce P.M. , Ramos-González E.J. , Ramos-García A.A. , Lara-Ramírez E.E. , Soriano-Herrera A.R. , Medellín-Luna M.F. , Valdez-Salazar F. , Castro-Garay C.Y. , Núñez-Contreras J. , De Donato-Capote M. , Sharma A. , Castañeda-Delgado J.E. , Zenteno-Cuevas R. , Enciso-Moreno J.A. , Licona-Cassani C. 
Published: March 2022

AbstractMycobacterium tuberculosis (Mtb) causes the majority of reported cases of human tuberculosis (TB), one of the deadliest infectious diseases worldwide. New diagnostic tools and approaches to detect drug-resistance must be introduced by 2025 to achieve the End-TB Strategy goals set for 2030 by the WHO. Genomic epidemiology of TB has allowed the expansion of catalogs listing genetic signatures of Mtb drug-resistance. However, very few Mtb strains from Latin America have participate in previous genomic epidemiologic efforts. Here we present the first functional genomic epidemiology study of drug-resistant Mtb strains in Mexico, incorporating the genomic characterization of 133 genomes, including 53 newly sequenced isolates, to provide a comprehensive phylogeographic analysis of drug resistant Mtb in Mexico. The study evidences the prevalence of Euro-American Lineage L4 (96.2%), featuring a uniform distribution of the sublineages X-type (33.08%), LAM (22.56%), and Haarlem (21.05%). Our results demonstrate low levels of agreement with traditional drug sensitivity tests (DST), raising concerns for drug-resistant isolates lacking any previously reported genetic signatures of resistance. Finally, we propose a novel functional networking tool (FuN-TB) to explore metabolic and cellular signatures of drug resistance. Applying functional genomics approaches to Latin American Mtb genomes will provide new drug-resistance screening targets that can contribute to bed side decision-making and advise local public policy.Abstract importanceWe presented the first phylogeographic analysis of Mycobacterium tuberculosis (Mtb) of Mexico. Our analysis integrates 133 genome sequences and is focused on the identification of genetic signatures associated to drug-resistance. The results show the geographic distribution of sublineages and drug-resistance phenotypic classes. Additionally, we propose a novel functional networking tool (FuN-TB) to explore metabolic and cellular signatures of drug resistance associated. We show for the first time that Mtb isolates from Mexico encode for region-specific genetic signarures of antimicrobial resistance. Applying functional genomics approaches to Latin American Mtb genomes will provide new drug-resistance screening targets that can contribute to bed side decision-making and advise local public policy.
The transcriptional profile of keloidal Schwann cells
Authors: Direder Martin , Wielscher Matthias , Weiss Tamara , Laggner Maria , Copic Dragan , Klas Katharina , Bormann Daniel , Vorstandlechner Vera , Tschachler Erwin , Ankersmit Hendrik Jan , Mildner Michael 
Published: March 2022

AbstractRecently, a specific Schwann cell type with pro-fibrotic and tissue regenerative properties has been identified that contributes to keloid formation. In the present study, we have reanalysed published single cell RNA sequencing (scRNAseq) studies of keloids, healthy skin and normal scars to reliably determine the specific gene expression profile of the keloid-specific Schwann cell type in more detail.We were able to confirm the presence of the repair-like, pro-fibrotic Schwann cell type in the datasets of all three studies and identified a specific gene set for these Schwann cells. In contrast to keloids, in normal scars the number of Schwann cells was neither increased nor was their gene expression profile distinctly different from Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the kruppel-like factor family and members of the immediate early response genes, in the de-differentiation process of keloidal Schwann cells.Together, our analysis strengthens the role of the pro-fibrotic Schwann cell type in the formation of keloids. Knowledge on the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.
Variant-specific burden of SARS-CoV-2 in Michigan: March 2020 through November 2021
Authors: Petrie Joshua G. , Eisenberg Marisa C. , Lauring Adam S. , Gilbert Julie , Harrison Samantha M. , DeJonge Peter M. , Martin Emily T. 
Published: March 2022

ABSTRACTAccurate estimates of total burden of SARS-CoV-2 are needed to inform policy, planning and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. COVID-19 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, and vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had ≥1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. Adults ≥80 years were more likely to be hospitalized or die if infected in fall 2020 than if infected during later waves. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.
Rethinking the nature of intraspecific variability and its consequences on species coexistence
Authors: Girard-Tercieux Camille , Maréchaux Isabelle , Clark Adam T. , Clark James S. , Courbaud Benoît , Fortunel Claire , Guillemot Joannès , Künstler Georges , Maire Guerric le , Pélissier Raphaël , Rüger Nadja , Vieilledent Ghislain 
Published: March 2022

AbstractContextIntraspecific variability (IV) has been proposed to explain species coexistence in diverse communities. Assuming, sometimes implicitly, that conspecific individuals can perform differently in the same environment and that IV blurs species differences, previous studies have found contrasting results regarding the effect of IV on species coexistence.ObjectiveWe aim at showing that the large IV observed in data does not mean that conspecific individuals are necessarily different in their response to the environment and that the role of high-dimensional environmental variation in determining IV has been largely underestimated in forest plant communities.Methods and ResultsWe first used a simulation experiment where an individual attribute is derived from a high-dimensional model, representing “perfect knowledge” of individual response to the environment, to illustrate how a large observed IV can result from “imperfect knowledge” of the environment. Second, using growth data from clonal Eucalyptus plantations in Brazil, we estimated a major contribution of the environment in determining individual growth. Third, using tree growth data from long-term tropical forest inventories in French Guiana, Panama and India, we showed that tree growth in tropical forests is structured spatially and that despite a large observed IV at the population level, conspecific individuals perform more similarly locally than compared with heterospecific individuals.SynthesisAs the number of environmental dimensions that are typically quantified is generally much lower than the actual number of environmental dimensions influencing individual attributes, a great part of observed IV might be misinterpreted as random variation across individuals when in fact it is environmentally-driven. This mis-representation has important consequences for inference about community dynamics. We emphasize that observed IV does not necessarily impact species coexistence per se but can reveal species response to high-dimensional environment, which is consistent with niche theory and the observation of the many differences between species in nature.
T cell migration requires ion and water influx to regulate actin polymerization
Authors: de Boer Leonard L. , Vanes Lesley , Melgrati Serena , O’May Joshua Biggs , Hayward Darryl , Driscoll Paul C. , Day Jason , Griffiths Alexander , Magueta Renata , Morrell Alexander , MacRae James I. , Köchl Robert , Tybulewicz Victor L. J. 
Published: March 2022

AbstractMigration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4+T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.One Sentence SummaryChemokine-induced migration of T cells requires water entry at the leading edge to facilitate actin polymerization.
Electroencephalography-derived functional connectivity in sensorimotor networks in Stroke and Multiple Sclerosis Fatigue
Authors: Wu Chi-Hsu , De Doncker William , Croce Pierpaolo , Bertoli Massimo , Tecchio Franca , Kuppuswamy Annapoorna 
Published: March 2022

AbstractA common mechanism of altered sensory processing is the basis of chronic fatigue in neurological disorders. Here we test the hypothesis ‘Altered connectivity in sensory networks underlies chronic fatigue in stroke and multiple sclerosis’.In 46 non-depressed, minimally impaired stroke survivors (n=29) and multiple sclerosis patients (n=17), median disease duration of 5 years, resting state neuronal activity was measured using 64-channel electroencephalography. Graph theory-based network analysis measure of functional connectivity (small-world index) was calculated in right and left motor (Brodmann areas 4, 6, 8, 9, 24 and 32) and somatosensory (Brodmann areas 1, 2, 3, 5, 7, 40 and 43) networks, in 5 frequency bands: delta, theta, alpha, beta and gamma. Fatigue was measured using Fatigue Severity Scale (Stroke) and modified Fatigue Impact Scale (MS), with scores of >4 (FSS) and >38 (mFIS), defined as high fatigue.Both stroke survivors and multiple sclerosis patients with high fatigue showed significantly more small-worldness in the right sensory networks in the beta band frequency. Additionally, only in stroke survivors with high fatigue, there was decreased small-worldness in the left motor network in the delta and theta bands.Altered sensory network connectivity is common to both stroke and MS fatigue, indicating impaired sensory processing as a disease-independent mechanism of chronic fatigue in neurological conditions. Furthermore, such difference in functional connectivity emerges in beta band activity, further strengthening the idea of altered sensorimotor processing as the basis of chronic neurological fatigue.
Engineering ecologically complementary rhizosphere probiotics using consortia of specialized bacterial mutants
Authors: Yang Chunlan , Li Jingxuan , Jousset Alexandre , Wang Xiaofang , Xu Zhihui , Yang Tianjie , Mei Xinlan , Zhong Zengtao , Xu Yangchun , Shen Qirong , Wei Zhong , Friman Ville-Petri 
Published: March 2022

AbstractWhile bacterial diversity is beneficial for the functioning of rhizosphere microbiomes, multi-species bioinoculants often fail to promote plant growth. One potential reason for this is that competition between inoculated consortia members create conflicts for their survival and functioning. To circumvent this, we used transposon mutagenesis to increase the functional diversity within Bacillus amyloliquefaciens bacterial species and tested if we could improve plant growth-promotion by assembling consortia of closely related but functionally specialized mutants. While most insertion mutations were harmful, some improved strains’ plant growth-promotion traits without increasing antagonism between them. Crucially, plant growth-promotion could be improved by applying these specialist mutants as consortia, leading to clear positive relationships between consortia richness, plant root colonization and protection from bacterial wilt disease. Together, our results suggest that increasing intra-species diversity could be an effective way to increase probiotic consortia multifunctionality, leading to more stable plant growth-promotion throughout growth cycle via insurance effects.
Case-only exome variation analysis of severe alcohol dependence using a multivariate hierarchical gene clustering approach
Authors: Gentry Amanda E. , Alexander Jeffry C. , Ahangari Mohammad , Peterson Roseann E. ,   VCU Alcohol Research Center working group, Miles Michael F. , Bettinger Jill C. , Davies Andrew G. , Groteweil Mike , Bacanu Silviu A. , Kendler Kenneth S. , Riley Brien P. , Webb Bradley T. 
Published: March 2022

ABSTRACTBackgroundVariation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria.ObjectiveLeverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes.MethodsFirst, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively.ResultsThree non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated.ConclusionThe proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence.
Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer
Authors: Brown Benjamin P. , Zhang Yun-Kai , Kim Soyeon , Finneran Patrick , Yan Yingjun , Du Zhenfang , Kim Jiyoon , Hartzler Abigail Leigh , LeNoue-Newton Michele L. , Smith Adam W. , Meiler Jens , Lovly Christine M. 
Published: March 2022

AbstractOncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15-30% of all non-small cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identify allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We build all-atom structural models of 60 ex19del variants identified in patients and combine ~400 μs of molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752>V, and L747_A750>P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752>V, the L747_A750>P variant forms highly active ligand-independent dimers. E746_S752>V displays the least TKI sensitivity among the variants tested, which enzyme kinetic analysis and TKI inhibition experiments suggest is due to increased ATP Km relative to the common E746_A750 variant. Through these analyses, we propose an expanded framework for interpreting ex19del variants and new considerations for therapeutic intervention.SignificanceEGFR mutations are detected in approximately 30% of all lung adenocarcinomas, and the most common EGFR mutation occurring in ~50% of patients is termed “exon 19 deletion” (ex19del). Despite the existence of dozens of different genomic variants comprising what is generically referred to clinically as ex19del, clinicians currently do not distinguish between ex19del variants in considering treatment options, and the differences between ex19del variants are largely unstudied in the broader scientific community. Herein, we describe functional differences between distinct EGFR ex19del variants attributable to the structural features of each variant. These findings suggest a possible explanation for observed differences in patient outcomes stratified by ex19del subtype and reinforce the need for allele-specific considerations in clinical treatment decision making.
Structure of dynein-dynactin on microtubules shows tandem recruitment of cargo adaptors
Authors: Chaaban Sami , Carter Andrew P. 
Published: March 2022

AbstractCytoplasmic dynein is a microtubule motor that is activated by its cofactor dynactin and a coiled-coil cargo adaptor. There is currently limited structural information on how the resulting complex interacts with microtubules and how adaptors are recruited. Here, we develop a cryo-EM processing pipeline to solve the high-resolution structure of dynein-dynactin and the adaptor BICDR1 bound to microtubules. This reveals the asymmetric interactions between neighbouring dynein motor domains and how it relates to their motile behaviour. We find unexpectedly that two adaptors occupy the complex. Both adaptors make similar interactions with the dyneins but diverge in their contacts with each other and dynactin. Our structure has implications for the stability and stoichiometry of motor recruitment by cargos.