bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in the response of different subtypes ofDrosophila melanogasterenteroendocrine cells to viral infections
Authors: Silva João M. F. , Nagata Tatsuya , Melo Fernando L. , Elena Santiago F. 
Published: July 2020

SummarySingle cell RNA sequencing (scRNA-seq) offers the possibility to monitor both host and pathogens transcriptomes at the cellular level. Here, public scRNA-seq data fromDrosophila melanogasterhave been used to compare the differences in replication strategy and cellular response between two viruses, Thika virus (TV) andD. melanogasterNora virus (DMelNV) in enteroendocrine cells (EEs). TV and DMelNV exhibited different patterns of replication and for TV, accumulation varied according to cell subtype. Cells infected with TV underwent down-regulation of genes that represent bottlenecks in the fruit fly interactome, while cells infected with DMelNV went through a down-expression of translation-related genes that represent both hubs and bottlenecks in the host interactome. In contrast, flies infected with DMelNV show only a systemic level down-regulation of bottleneck genes. Here, we use scRNA-seq to highlight the differences and commonalities between cellular response to TV and DMelNV and between cellular and systemic response to DMelNV.
Identification of differentially expressed genes in the longissimus dorsi muscle of Luchuan and Duroc pigs by transcriptome sequencing
Authors: Pan Pengcheng , Qin Zhaoxian , Xie Wan , Jiao Di , Chen Baojian , Guan Zhihui , Xie Bingkun 
Published: July 2020

AbstractThe Duroc pig originated in the United States and is a typical lean meat pig. The breed grows fast and the body size is large, but the meat quality is poor. The Luchuan pig is one of the eight local excellent breeds in China; it has tender meat but a small size. To study the factors that determine growth, we selected the longissimus dorsi muscle of Luchuan and Duroc pigs for transcriptome sequencing. The results of transcriptome showed that 3682 genes were differentially expressed (DEGs) in the longissimus dorsi muscle of Duroc and Luchuan pigs. We screened out forty genes related to muscle development and selected the Myosin light chain-2 (MYL2) gene to perform preliminary research. Gene Ontology (GO) enrichment of biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that most of the forty gene were mainly involved in the Akt/FoxO signaling pathway, Fatty acid metabolism, Arachidonic acid metabolism and Glycine, serine and threonine metabolism. Such pathways contributed to skeletal muscle growth, fatty acid metabolism and intramuscular fat deposition. These results provide insight into the mechanisms underlying the formation of skeletal muscle and provide candidate genes to improve growth traits and meat quality traits, as well as contribute to improving the growth and development traits of pigs through molecular breeding.
Association of the invasiveHaemaphysalis longicornistick with vertebrate hosts, other native tick vectors, and tick-borne pathogens in New York City
Authors: Tufts Danielle M. , Goodman Laura B. , Benedict Meghan C. , Davis April D. , VanAcker Meredith C. , Diuk-Wasser Maria 
Published: July 2020

AbstractHaemaphysalis longicornis, the Asian longhorned tick, is an invasive ixodid tick that has rapidly spread across the northeastern and southeastern regions of the United States since first reported in 2017. The emergence ofH. longicornispresents a potential threat for livestock, wildlife, and human health as the host associations and vector potential of this invasive pest in the United States are poorly understood. Previous field data from the United States has shown thatH. longicorniswas not associated with natural populations of small mammals or birds, but they show a preference for medium sized mammals in laboratory experiments. Therefore, medium and large sized mammals were sampled on Staten Island, New York to determineH. longicornishost associations and vector potential for a range of human and veterinary pathogens. A total of 97 hosts were sampled and five species of tick (Amblyomma americanum, Dermacentor variabilis, H. longicornis, Ixodes scapularis, Ixodes cookei) were found feeding concurrently on these hosts.Haemaphysalis longicorniswas found in the highest proportions compared to other native tick species on raccoons (55.4%), Virginia opossums (28.9%), and white-tailed deer (11.5%). Tissue, blood, and engorged larvae were tested for 17 different pathogens using a nanoscale PCR platform. Infection with five pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, Rickettsiaspp.,Mycoplasma haemocanis, andBartonellaspp.) was detected in host samples, but no pathogens were found in any larval samples. These results suggest that although large and medium sized mammals feed large numbers ofH. longicornisticks in the environment there is presently a low potential forH. longicornisto acquire pathogens from these wildlife hosts.HighlightsH. longicorniswere sampled from seven genera of large and medium-sized mammalsRaccoons, opossums, and white-tailed deer fed a large proportion ofH. longicornisH. longicornisdid not acquire pathogens through co-feeding with native tick vectorsHost species were infected with a range of pathogens of human and veterinary concernHost-derivedH. longicornisengorged larvae were not infected with any pathogens
DFG-1 residue controls inhibitor binding mode and affinity providing a basis for rational design of kinase inhibitor selectivity
Authors: Schröder Martin , Bullock Alex N. , Federov Oleg , Bracher Franz , Chaikuad Apirat , Knapp Stefan 
Published: July 2020

ABSTRACTSelectivity remains a challenge for ATP-mimetic kinase inhibitors, an issue that may be overcome by targeting unique residues or binding pockets. However, to date only few strategies have been developed. Here we identify that bulky residues located N-terminal to the DFG motif (DFG-1) represent an opportunity for designing highly selective inhibitors with unexpected binding modes. We demonstrate that several diverse inhibitors exerted selective, non-canonical binding modes that exclusively target large hydrophobic DFG-1 residues present in many kinases including PIM, CK1, DAPK and CLK. Using the CLK family as a model, structural and biochemical data revealed that the DFG-1 valine controlled a non-canonical binding mode in CLK1, providing a rational for selectivity over the closely-related CLK3 which harbors a smaller DFG-1 alanine. Our data suggests that targeting the restricted back pocket in the small fraction of kinases that harbor bulky DFG-1 residues offers a versatile selectivity filter for inhibitor design.
Protein kinase A catalytic-α and catalytic-β proteins have non-redundant functions
Authors: Raghuram Viswanathan , Salhadar Karim , Limbutara Kavee , Park Euijung , Yang Chin-Rang , Knepper Mark A. 
Published: July 2020

ABSTRACTVasopressin regulates osmotic water transport in the renal collecting duct by PKA-mediated control of the water channel aquaporin-2 (AQP2). Collecting duct principal cells express two seemingly redundant PKA catalytic subunits, PKA catalytic α (PKA-Cα) and PKA catalytic β (PKA-Cβ). To identify the roles of these two protein kinases, we carried out deep phosphoproteomic analysis in cultured mpkCCD cells in which either PKA-Cα or PKA-Cβ was deleted using CRISPR-Cas9-based genome editing. Controls were cells carried through the genome editing procedure, but without deletion of PKA. TMT mass tagging was used for protein mass spectrometric quantification. Of the 4635 phosphopeptides that were quantified 67 were significantly altered in abundance with PKA-Cα deletion, while 21 were significantly altered in abundance with PKA-Cβ deletion. However, only four sites were changed in both. The target proteins identified in PKA-Cα-null cells were largely associated with cell membranes and membrane vesicles, while target proteins in the PKA-Cβ-null cells were largely associated with the actin cytoskeleton and cell junctions. In contrast, in vitro incubation of mpkCCD proteins with recombinant PKA-Cα and PKA-Cβ resulted in virtually identical phosphorylation changes. In addition, analysis of total protein abundances in the in vivo samples showed that PKA-Cα deletion resulted in a near disappearance of AQP2 protein, while PKA-Cβ deletion did not decrease AQP2 abundance. We conclude that PKA-Cα and PKA-Cβ serve substantially different functions in renal collecting duct cells and that differences in phosphorylation targets may be due to differences in protein interactions, e.g. mediated by AKAP, C-KAP or PDZ binding.
Chronic activation of fear engrams induces extinction-like behavior in ethanol-exposed mice
Authors: Cincotta Christine , Murawski Nathen J. , Grella Stephanie L. , McKissick Olivia , Doucette Emily , Ramirez Steve 
Published: July 2020

ABSTRACTAlcohol withdrawal directly impacts the brain’s stress and memory systems, which may underlie individual susceptibility to persistent drug and alcohol-seeking behaviors. Numerous studies demonstrate that forced alcohol abstinence, which may lead to withdrawal, can impair fear-related memory processes in rodents such as extinction learning, however the underlying neural circuits mediating these impairments remain elusive. Here, we tested an optogenetic strategy aimed at mitigating fear extinction impairments in male c57BL/6 mice following exposure to alcohol (i.e., ethanol) and forced abstinence. In the first experiment, extensive behavioral extinction training in a fear-conditioned context was impaired in ethanol-exposed mice compared to controls. In the second experiment, neuronal ensembles processing a contextual fear memory in the dorsal hippocampus were tagged and optogenetically reactivated repeatedly in a distinct context in ethanol-exposed and control mice. Chronic activation of these cells resulted in a context-specific, extinction-like reduction in fear responses in both control and ethanol-exposed mice. These findings suggest that while ethanol can impair fear extinction learning, optogenetic manipulation of a fear engram is sufficient to induce an extinction-like reduction in fear responses.
Lack of support for Deuterostomia prompts reinterpretation of the first Bilateria
Authors: Kapli Paschalia , Natsidis Paschalis , Leite Daniel J. , Fursman Maximilian , Jeffrie Nadia , Rahman Imran A. , Philippe Hervé , Copley Richard R. , Telford Maximilian J. 
Published: July 2020

AbstractThe bilaterally symmetric animals (Bilateria) are considered to comprise two monophyletic groups, Protostomia and Deuterostomia. Protostomia contains the Ecdysozoa and the Lophotrochozoa; Deuterostomia contains the Chordata and the Xenambulacraria (Hemichordata, Echinodermata and Xenacoelomorpha). Their names refer to a supposed distinct origin of the mouth (stoma) in the two clades, but these groups have been differentiated by other embryological characters including embryonic cleavage patterns and different ways of forming their mesoderm and coeloms. Deuterostome monophyly is not consistently supported by recent studies. Here we compare support for Protostomia and Deuterostomia using five recently published, phylogenomic datasets. Protostomia is always strongly supported, especially by longer and higher quality genes. Support for Deuterostomia is always equivocal and barely higher than support for paraphyletic alternatives. Conditions that can cause tree reconstruction errors - inadequate models, short internal branch, faster evolving genes, and unequal branch lengths - correlate with statistical support for monophyletic deuterostomes. Simulation experiments show that support for Deuterostomia could be explained by systematic error. A survey of molecular characters supposedly diagnostic of deuterostomes shows many are not valid synapomorphies. The branch between bilaterian and deuterostome common ancestors, if real, is very short. This finding fits with growing evidence suggesting the common ancestor of all Bilateria had many deuterostome characteristics. This finding has important implications for our understanding of early animal evolution and for the interpretation of some enigmatic Cambrian fossils such as vetulicolians and banffiids.
Surface-Based Connectivity Integration
Authors: Cole Martin , Murray Kyle , St-Onge Etienne , Risk Benjamin , Zhong Jianhui , Schifitto Giovanni , Descoteaux Maxime , Zhang Zhengwu 
Published: July 2020

AbstractThere has been increasing interest in jointly studying structural connectivity (SC) and functional connectivity (FC) derived from diffusion and functional MRI. However, several fundamental problems are still not well considered when conducting such connectome integration analyses, e.g., “Which structure (e.g., gray matter, white matter, white surface or pial surface) should be used for defining SC and FC and exploring their relationships”, “Which brain parcellation should be used”, and “How do the SC and FC correlate with each other and how do such correlations vary in different locations of the brain?”. In this work, we develop a new framework calledsurface-based connectivity integration(SBCI) to facilitate the integrative analysis of SC and FC with a re-thinking of these problems. We propose to use the white surface (the interface of white matter and gray matter) to build both SC and FC since diffusion signals are in the white matter while functional signals are more present in the gray matter. SBCI also represents both SC and FC in a continuous manner at very high spatial resolution on the white surface, avoiding the need of pre-specified atlases which may bias the comparison of SC and FC. Using data from the Human Connectome Project, we show that SBCI can create reproducible, high quality SC and FC, in addition to three novel imaging biomarkers reflective of the similarity between SC and FC throughout the brain, called global, local, and discreteSC-FC coupling. Further, we demonstrate the usefulness of these biomarkers in finding group effects due to biological sex throughout the brain.
Species traits predict extinction risk across the Tree of Life
Authors: Chichorro Filipe , Urbano Fernando , Teixeira Dinarte , Väre Henry , Pinto Tiago , Brummitt Neil , He Xiaolan , Hochkirch Axel , Hyvönen Jaakko , Kaila Lauri , Juslén Aino , Cardoso Pedro 
Published: July 2020

SummaryBiodiversity is eroding at unprecedented rates due to human activity1. Species’ trajectories towards extinction are shaped by multiple factors, including life-history traits2as well as human pressures3. Previous studies linking these factors to extinction risk have been narrow in their taxonomic and geographic scope4, thus limiting the ability for identifying global predictors. We studied the relation between 12 traits and the extinction risk of almost 900 species representing 15 groups across the tree of life (vertebrates, invertebrates and plants) at a global scale. We show that threatened species share narrow habitat breadth, poor dispersal ability, low fecundity, small altitudinal range, and are affected by a large human footprint. Other traits either show contrasting responses among groups (body size, offspring size, and change in human footprint), or relations were found for only a limited number of taxa (generation length, diet breadth, microhabitat). Our study suggests that in the absence of data on the precise distribution and population trends of species, traits can be used as predictors of extinction risk and thus help guide future research, monitoring and conservation efforts.
Smoothened Transduces Hedgehog Signals via Activity-Dependent Sequestration of PKA Catalytic Subunits
Authors: Arveseth Corvin D. , Happ John T. , Hedeen Danielle S. , Zhu Ju-Fen , Capener Jacob L. , Shaw Dana Klatt , Deshpande Ishan , Liang Jiahao , Xu Jiewei , Stubben Sara L. , Nelson Isaac B. , Walker Madison F. , Krogan Nevan J. , Grunwald David J. , Hüttenhain Ruth , Manglik Aashish , Myers Benjamin R. 
Published: July 2020

ABSTRACTThe Hedgehog (Hh) pathway is essential for organ development, homeostasis, and regeneration. Dysfunction of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Here we show that, rather than conforming to traditional GPCR signaling paradigms, SMO activates GLI by binding and sequestering protein kinase A (PKA) catalytic subunits at the membrane. This sequestration, triggered by GPCR kinase 2 (GRK2)-mediated phosphorylation of SMO intracellular domains, prevents PKA from phosphorylating soluble substrates, releasing GLI from PKA-mediated inhibition. Our work provides a mechanism directly linking Hh signal transduction at the membrane to GLI transcription in the nucleus. This process is more fundamentally similar between species than prevailing hypotheses suggest. The mechanism described here may apply broadly to other GPCR- and PKA-containing cascades in diverse areas of biology.
Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine
Authors: Chiuppesi Flavia , Salazar Marcela d’Alincourt , Contreras Heidi , Nguyen Vu H , Martinez Joy , Park Soojin , Nguyen Jenny , Kha Mindy , Iniguez Angelina , Zhou Qiao , Kaltcheva Teodora , Levytskyy Roman , Ebelt Nancy D , Kang Tae Hyuk , Wu Xiwei , Rogers Thomas , Manuel Edwin R , Shostak Yuriy , Diamond Don J , Wussow Felix 
Published: July 2020

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.
Transcriptome analysis of alternative splicing-coupled nonsense-mediated mRNA decay in human cells reveals broad regulatory potential
Authors: French Courtney E. , Wei Gang , Lloyd James P. B. , Hu Zhiqiang , Brooks Angela N. , Brenner Steven E. 
Published: July 2020

AbstractTo explore the regulatory potential of nonsense-mediated mRNA decay (NMD) coupled with alternative splicing, we globally surveyed the transcripts targeted by this pathway via RNA-Seq analysis of HeLa cells in which NMD had been inhibited. We identified putative NMD-targeted transcripts as those with a termination codon more than 50 nucleotides upstream of an exon-exon junction (premature termination as defined by the ‘50nt rule’) and that significantly increased in abundance upon NMD inhibition. We additionally controlled for potential transcriptional up-regulation by requiring the putative NMD targets to increase in abundance substantially more than the isoforms from the same gene that do not contain a premature termination codon. This resulted in a conservative set of 2,793 transcripts derived from 2,116 genes as physiological NMD targets (9.2% of expressed transcripts and >20% of alternatively spliced genes). Our analysis identified previously inferred unproductive isoforms and numerous heretofore-uncharacterized ones. NMD-targeted transcripts were derived from genes involved in many functional categories, and are particularly enriched for RNA splicing genes as well as for those harboring ultraconserved elements. By investigating the features of all transcripts impacted by NMD, we find that the 50nt rule is a strong predictor of NMD degradation while 3’ UTR length on its own generally has only a small effect in this human cell line. Additionally, thousands more transcripts without a premature termination codon in the main coding sequence contain a uORF and display significantly increased abundance upon NMD inhibition indicating potentially widespread regulation through decay coupled with uORF translation. Our results support that alternative splicing coupled with NMD is a prevalent post-transcriptional mechanism in human cells with broad potential for biological regulation.
mutyper: assigning and summarizing mutation types for analyzing germline mutation spectra
Authors: DeWitt William S. 
Published: July 2020

AbstractSummaryCharacterization of germline mutation spectrum variation from population genomics data has shed light on the biological complexity of the mutation process, and its evolution within and between species. This analysis augments available population SNP data with estimates of local ancestral genomic context to assign mutation types and aggregate summary statistics thereof, and is increasingly common. There is a need for standardized computational tools to extract mutation spectrum information from sequencing data. Here I describemutyper, a command-line utility and Python package that uses an ancestral genome estimate to assign mutation types to SNP data, compute mutation spectra for individuals, and compute sample frequency spectra resolved by mutation type for population genetic inference.Availability and implementationmutypercan be installed using the pip package manager and is compatible with Python 3.6+. Documentation is provided athttps://harrispopgen.github.io/mutyper; source code is available athttps://github.com/harrispopgen/mutyper.
All hands on deck: Large-scale (re)sculpting of cortical circuits in post-resection children
Authors: Maallo Anne Margarette S. , Granovetter Michael C. , Freud Erez , Kastner Sabine , Pinsk Mark A. , Patterson Christina , Behrmann Marlene 
Published: July 2020

AbstractDespite the relative successes in the surgical treatment of pharmacoresistant epilepsy, there is rather little research on the neural (re)organization that potentially subserves behavioral compensation. Here, we examined the post-surgical functional connectivity (FC) in children and adolescents who have undergone unilateral cortical resection and, yet, display remarkably normal behavior. Conventionally, FC has been investigated in terms of the mean correlation of the BOLD time courses extracted from different brain regions. Here, we demonstrated the value of segregating the voxel-wise relationships into mutually exclusive populations that were either positively or negatively correlated. While, relative to controls, the positive correlations were largely normal, negative correlations among networks were increased. Together, our results point to reorganization in the contralesional hemisphere, possibly suggesting competition for cortical territory due to the demand for representation of function. Conceivably, the ubiquitous negative correlations enable the differentiation of function in the reduced cortical volume following a unilateral resection.