bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent and distributed effects of the schizophrenia-associated 3q29 deletion on the human neural transcriptome
Authors: Sefik Esra , Purcell Ryan H. ,   The Emory 3q29 Project, Walker Elaine F. , Bassell Gary J. , Mulle Jennifer G. 
Published: May 2020

AbstractThe 3q29 deletion (3q29Del) confers >40-fold increased risk for schizophrenia. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, post-translational modifications, chromatin remodeling and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological post-mortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.
Far-red light enhances soluble sugar levels andBotrytis cinereadisease development in tomato leaves in a jasmonate-dependent manner
Authors: Courbier Sarah , Grevink Sanne , Sluijs Emma , Bonhomme Pierre-Olivier , Kajala Kaisa , Van Wees Saskia C.M. , Pierik Ronald 
Published: May 2020

SummaryPlants lacking phytochrome photoreceptors display elevated soluble sugar levels in leaves. Although pathogens principally feed on sugars supplied by the plant, the link between increased plant sugar levels upon phytochrome inactivation and disease development has not been considered.Tomato plants were exposed to control white LED (WL) or a combination of white and far-red LED (WL+FR) light, to inactivate phytochrome signaling and modulate soluble sugar levels. We also experimentally manipulated internal sugar levels by either supplementing glucose or inhibiting photosynthesis in tomato leaflets prior to performing soluble sugar quantifications or bioassays with pathogens.Tomato plants exposed to WL+FR or lacking phytochrome B (phyB1phyB2double mutants) show enhanced levels of soluble sugars, especially glucose and fructose, in their leaves. The jasmonic acid biosynthesis mutantdef1also has elevated soluble sugar levels, which could be rescued by exogenous methyl-jasmonate application. This indicates an interplay between JA signaling and primary metabolism.The increase in soluble sugar levels in tomato leaves upon phytochrome inactivation is regulated in a JA-dependent manner. Our data stress the importance of primary metabolism in the FR-induced susceptibility in tomato that could contribute to promote plant resistance when grown at high density.
Prediction of disordered regions in proteins with recurrent Neural Networks and protein dynamics
Authors: Orlando Gabriele , Raimondi Daniele , Codice Francesco , Tabaro Francesco , Vranken Wim 
Published: May 2020

AbstractThe role of intrinsically disordered protein regions (IDRs) in cellular processes has become increasingly evident over the last years. These IDRs continue to challenge structural biology experiments because they lack a well-defined conformation, and bioinformatics approaches that accurately delineate disordered protein regions remain essential for their identification and further investigation. Typically, these predictors use only the protein amino acid sequence, without taking into account likely emergent properties that are sequence context dependent, such as protein backbone dynamics.The DisoMine method predicts protein disorder with recurrent neural networks not directly from the amino acid sequence, but instead from more generic predictions of key biophysical properties, here protein dynamics, secondary structure and early folding. The tool is fast and requires only a single sequence, making it applicable for large-scale screening, including poorly studied and orphan proteins. DisoMine compares well to 10 state of the art predictors, also if these use evolutionary information.DisoMine is freely available through an interactive webserver athttp://bio2byte.com/disomine/
Human melanocyte development and melanoma dedifferentiation at single cell resolution
Authors: Belote Rachel L. , Le Daniel , Maynard Ashley , Lang Ursula E. , Sinclair Adriane , Planells-Palop Vicente , Baskin Laurence , Tward Aaron D. , Darmanis Spyros , Judson-Torres Robert L. 
Published: May 2020

SUMMARYIn humans, epidermal melanocytes are responsible for skin pigmentation, defense against ultraviolet radiation, and the deadliest common skin cancer, melanoma. While there is substantial overlap in melanocyte development pathways between different model organisms, species dependent differences are frequent and the conservation of these processes in human skin remains unresolved1–3. Thus, the biology of developing and adult human melanocytes remains largely uncharacterized. Here, we used a single-cell enrichment and RNA-sequencing pipeline to study human epidermal melanocytes derived directly from skin, capturing transcriptomes across different anatomic sites, developmental age, sexes, and multiple skin tones. Using donor-matched skin from distinct volar and non-volar anatomic locations, we uncovered subpopulations of melanocytes exhibiting site-specific enrichment that occurs during gestation and persists through adulthood. In addition, we identified human melanocyte differentiation transcriptional programs that are distinct from gene signatures generated from model systems. Finally, we use these programs to define patterns of dedifferentiation that are predictive of melanoma prognosis. Overall, the characterization of human melanocytes fresh from skin revealed new subpopulations, human-specific transcriptional programs, and valuable insights into melanoma dedifferentiation.
Development of microsatellite markers for a giant water bug,Appasus japonicus, distributed in East Asia
Authors: Suzuki Tomoya , Hirao Akira S. , Takenaka Masaki , Yano Koki , Tojo Koji 
Published: May 2020

AbstractWe developed microsatellite markers forAppasus japonicus(Hemiptera: Belostomatidae). This belostomatid bug is distributed in East Asia (Japanese Archipelago, Korean Peninsula, and Mainland China), and often listed as endangered species in the ‘Red List’ or the ‘Red Data Book’ at the national and local level in Japan. Here we describe twenty novel polymorphic microsatellite loci developed forA. japonicus, and marker suitability was evaluated on 56 individuals from fourA. japonicuspopulations (Nagano, Hiroshima, and Yamaguchi prefecture, Japan, and Chungcheongnam-do, Korea). The number of alleles per locus ranged 1–12 (mean = 2.5), and average observed and expected heterozygosity, and fixation index per locus were 0.270, 0.323, and 0.153, respectively. The 20 markers described here will be useful for investigating the genetic structure ofA. japonicuspopulations, which can contribute in population genetics studies of this species.
Viewing communities as coupled oscillators: elementary forms from Lotka and Volterra to Kuramoto
Authors: Hajian-Forooshani Zachary , Vandermeer John 
Published: May 2020

AbstractEcosystems and their embedded ecological communities are almost always by definition collections of oscillating populations. This is apparent given the qualitative reality that oscillations emerge from consumer-resource interactions, which are the simple building blocks for ecological communities. It is also likely always the case that oscillatory consumer-resource pairs will be connected to one another via trophic cross-feeding with shared resources or via competitive interactions among resources. Thus, one approach to understanding the dynamics of communities conceptualizes them as collections of oscillators coupled in various arrangements. Here we look to the pioneering work of Kuramoto on coupled oscillators and ask to what extent can his insights and approaches be translated to ecological systems. We explore all possible coupling arrangements of the simple case of three oscillator systems with both the Kuramoto model and with the classical Lotka-Volterra equations that are foundational to ecology. Our results show that the six-dimensional analogous Lotka-Volterra systems behave strikingly similarly to that of the corresponding Kuramoto systems across all possible coupling combinations. This qualitative similarity in the results between these two approaches suggests that a vast literature on coupled oscillators that has largely been ignored by ecologists may in fact be relevant in furthering our understanding of ecosystem and community organization.
Activation of the Anaphase Promoting Complex reverses multiple drug resistant cancer
Authors: Arnason T.G. , MacDonald-Dickinson V. , Davies J.F. , Lobanova L. , Gaunt C. , Trost B. , Waldner M. , Baldwin P. , Borrowman D. , Marwood H. , Gillespie Z.E. , Vizeacoumar F.S. , Vizeacoumar F.J. , Eskiw C.H. , Kusalik A. , Harkness T.A.A. 
Published: May 2020

ABSTRACTLike humans, canines spontaneously develop lymphomas that are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make them excellent models to study MDR mechanisms. We previously demonstrated that adjunct treatment ofin vitroMDR cell lines with insulin-sensitizers effectively restored MDR chemosensitivity and prevented MDR development. This study extends the use of an insulin-sensitizer to clinical and tumor responsesin vivoin volunteer canines with MDR lymphoma, including assessing changes in MDR protein biomarkers and global gene expression. Longitudinal tumor sampling and analysis of MDR cases throughout treatment allowed a correlation betweenin vivomolecular mechanisms and clinical responsiveness. We found reduced MDR biomarkers within all tumors, yet only one canine entered clinical remission. Analysis of tumor samples during remission and relapse allowed comparison of gene expression profiles. This revealed the Anaphase Promoting Complex (APC), a ubiquitin-E3 ligase regulating cell cycle progression, was impaired during chemoresistance/MDR and restored during remission. Validatingin vitrotests restored MDR chemosensitivity upon APC activation, supporting the idea that APC activity is an important underlying cellular mechanism associated with treatment resistance, and a novel potential therapeutic target.
Fear learning sculpts functional brain connectivity at rest beyond the traditional fear network in humans
Authors: Fraenz Christoph , Metzen Dorothea , Merz Christian J. , Selpien Helene , Friedrich Patrick , Ocklenburg Sebastian , Axmacher Nikolai , Genç Erhan 
Published: May 2020

AbstractNeuroscientific research has identified specific brain networks involved in the acquisition of fear memories. Using fMRI to assess changes in resting-state functional connectivity (RSFC) induced by fear acquisition, single brain regions from these networks have also been linked to fear memory consolidation. However, previous studies only examined RSFC changes within restricted sets of brain regions or without a proper control group, leaving our knowledge about fear consolidation outside of traditional fear networks incomplete. Here, we tested a group of 84 healthy participants in a differential fear conditioning paradigm and quantified RSFC changes between 358 cortical and 16 subcortical brain areas. Subsequent to fear learning, 21 functional connections exhibited significant RSFC changes. Importantly, these connections were not restricted to the traditional fear networks but also comprised various frontal and visual areas. Our findings indicate that fear memory consolidation is a complex process that integrates relevant information across the entire brain.
Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time
Authors: Barnes Kayla G. , Lachenauer Anna E. , Nitido Adam , Siddiqui Sameed , Gross Robin , Beitzel Brett , Siddle Katherine J. , Freije Catherine A. , Dighero-Kemp Bonnie , Mehta Samar , Carter Amber , Uwanibe Jessica , Ajogbasile Fehintola , Olumade Testimony J. , Odia Ikponmwosa , Sandi John Demby , Momoh Mambu , Metsky Hayden C. , Boehm Chloe K. , Lin Aaron E. , Kemball Molly , Park Daniel J. , Grant Donald S. , Happi Christian T. , Branco Luis , Boisen Matt , Sullivan Brian M. , Amare Mihret , Tiamiyu Abdulwasiu , Parker Zahra , Iroezindu Michael , Modjarrad Kayvon , Myhrvold Cameron , Garry Robert F. , Palacios Gustavo , Hensley Lisa E. , Schaffner Stephen F. , Colubri Andres , Sabeti Pardis C. 
Published: May 2020

AbstractViral hemorrhagic fevers (VHFs) remain some of the most devastating human diseases, and recent outbreaks of Ebola virus disease (EVD)1,2and Lassa fever (LF)3,4highlight the urgent need for sensitive, field-deployable tests to diagnose them5,6. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. Our EBOV diagnostic detects both theLandNPgenes, thereby eliminating the potential for false positive results caused by the rVSVΔG-ZEBOV-GP live attenuated vaccine. Our two LASV diagnostics together capture 90% of known viral diversity and demonstrate that CRISPR-RNAs (crRNAs) can be effectively multiplexed to provide greater coverage of known viral diversity. We performed safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating and chemically treating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We developed a user-friendly field protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deployed our tests in Sierra Leone and Nigeria in response to recent outbreaks.
Development and validation of IMMUNO-COV™: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2
Authors: Vandergaast Rianna , Carey Timothy , Reiter Samantha , Lech Patrycja , Gnanadurai Clement , Tesfay Mulu , Buehler Jason , Suksanpaisan Lukkana , Naik Shruthi , Brunton Bethany , Recker Jordan , Haselton Michelle , Ziegler Christopher , Roesler Anne , Mills John R. , Theel Elitza , Weaver Scott C. , Rafael Grace , Roforth Matthew M. , Jerde Calvin , Tran Sheryl , Diaz Rosa Maria , Bexon Alice , Baum Alina , Kyratsous Christos A. , Peng Kah Whye , Russell Stephen J. 
Published: May 2020

AbstractWe here describe the development and validation of IMMUNO-COV™, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-Δ19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-Δ19CT infection was blocked by monoclonal α-SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of α-SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNTEC50 values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV™ assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.
Defining the familial fold of the vicilin-buried peptide family
Authors: Payne Colton D. , Vadlamani Grishma , Fisher Mark F. , Zhang Jingjing , Clark Richard J. , Mylne Joshua S. , Rosengren K. Johan 
Published: May 2020

ABSTRACTPlants and their seeds have been shown to be a rich source of cystine-stabilized peptides. Recently a new family of plant seed peptides whose sequences are buried within precursors for seed storage vicilins was identified. Members of this Vicilin Buried Peptide (VBP) family are found in distantly related plant species including the monocot date palm, as well as dicotyledonous species like pumpkin and sesame. Genetic evidence for their widespread occurrence indicates that they are of ancient origin. Limited structural studies have been conducted on VBP family members, but two members have been shown to adopt a helical hairpin fold. We here present an extensive characterization of VBPs using solution NMR spectroscopy, to better understand their structural features. Four peptides were produced by solid phase peptide synthesis and shown to adopt a helix-loop-helix hairpin fold, as a result of the I-IV/II-III ladder-like connectivity of their disulfide bonds. Inter-helix interactions, including hydrophobic contacts and salt bridges, are critical for the fold stability and control the angle at which the anti-parallel α-helices interface. Activities reported for VBPs include trypsin inhibitory activity and inhibition of ribosomal function, however their diverse structural features despite a common fold suggest additional bioactivities yet to be revealed are likely.
Isolation And Identification Of Major Pathogenic Bacteria From Clinical Mastitic Cows In Asella Town, Ethiopia
Authors: Tufa Gezehagn Kasa , Muluneh Betelhem Tegegne , Siyamregn Belege Tadesse 
Published: May 2020

ABSTRACTMastitis is a multi-etiological and complex disease causing inflammation of parenchyma of mammary glands is a problem in many dairy herds. The objective of this study was isolation and identification of the pathogenic bacteria that cause bovine clinical mastitis. A cross sectional study was undertaken from November 2018 to April 2019 on small scale and government dairy farms in Asella town. Cows were examined directly at quarter and teat level for clinical manifestation. A total of 83 milk samples were collected from 46 cows that shows clinical sign of mastitis from a total of 12 farms. Isolation and identification of major bacterial species was carried out by culturing on different media and using primary and secondary biochemical tests. Out of the 83 samples collected and examined, all (100%) were positive for cultural isolation of bacterial species. The bacteria were identified to genus and species level. Among the 83 isolates 32 (38.6%) wereS. aureus, 24 (28.9%) wereStaphylococcus intermediusand 6 (7.2%) wereStaphyloco ccus hyicus, other bacteria likeEscherichia coli12(14.5%), Streptococcus species 2 (2.4%) were also isolated. Bacillus Species 2 (2.4%), Proteus species 2(2.4%) and 3 (3.6%) of them were mixed bacterial infections. The present study revealed that both contagious and environmental bacterial pathogens were responsible for the occurrence of clinical mastitis. Proper milking practices and farm husbandry practices as well as future detailed studies up to the species level and on antibiotic profiles of the pathogens are needed.
Vpr R36W and R77Q Mutations Alter HIV-1 Replication and Cytotoxicity in T Lymphocytes
Authors: Solis-Leal Antonio , Karlinsey Dalton C. , Lopez J. Brandon , Planelles Vicente , Poole Brian D. , Berges Bradford K. 
Published: May 2020

AbstractChronic immune inflammation (CII) is a characteristic symptom of HIV-1 infection that contributes to acquired immunodeficiency syndrome (AIDS) progression in infected patients. Distinct AIDS development rates have shown that there are Rapid Progressor (RP) and Long-Term Non-Progressor (LTNP) patients, but the circumstances governing these differences in disease progression are poorly understood. Mutations in the Viral Protein R (Vpr) have been suggested to have a direct impact on disease progression. Studies have shown that Vpr interacts with both host and viral factors; these interactions affect cellular activities such as cell cycle progression and enhancement of apoptosis. The Vpr mutants R36W and R77Q have been associated with RP and LTNP phenotypes, respectively; however, these findings are still controversial. This study sheds light on the effects that Vpr mutations have in the context of HIV-1 infection of the HUT78 T cell line, using replication-competent CXCR4-tropic virus strains. Our results show a replication enhancement of the R36W mutant (increased viral load and percentage of p24+ cells) accompanied by increased cytotoxicity. Interestingly, the R77Q mutant showed a unique enhancement of apoptosis (measured by Annexin V and TUNEL staining) and G2 cell cycle arrest; these effects were not seen with WT or R36W viruses. Since necrosis is associated with the release of pro-inflammatory factors, the R36 mutation could lead to more robust CII and the RP phenotype. Conversely, the R77Q mutation leads to apoptosis, potentially avoiding CII and leading to a LTNP phenotype. Thus, Vpr mutations may impact HIV-1 related progression to AIDS.ImportanceThevprgene is thought to be an important virulence factor in Human Immunodeficiency Virus type 1 (HIV-1).vprpolymorphisms have been associated with different rates of acquired immunodeficiency syndrome (AIDS) progression. However, there is controversy about the cytopathic and virulence phenotypes of Vpr mutants, with contradictory conclusions about the same mutants. Here, we examine the replication capacity, apoptosis induction, and G2 cell cycle arrest phenotypes of threevprmutants compared to wild-type HIV-1. One mutant associated with rapid AIDS progression replicated more efficiently and killed cells more rapidly than wild-type HIV-1. Another mutant associated with slow AIDS progression triggered apoptosis more efficiently than wild-type HIV-1. These results shed additional light on the role ofvprpolymorphisms in T cell killing by HIV-1 and may help to explain the role of Vpr in different rates of AIDS progression.