bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hybrid stochastic-deterministic approach to explore multiple infection and evolution in HIV
Authors: Kreger Jesse , Komarova Natalia L. , Wodarz Dominik 
Published: September 2020

AbstractTo study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small subpopulations coexist. Here, we describe a hybrid stochastic-deterministic algorithm to simulate mutant evolution in large viral populations, such as acute HIV-1 infection, and further include the multiple infection of cells. We demonstrate that the hybrid method can approximate the fully stochastic dynamics with sufficient accuracy at a fraction of the computational time, and quantify evolutionary end points that cannot be expressed by deterministic models, such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We apply this method to study the role of multiple infection and intracellular interactions among different virus strains (such as complementation and interference) for mutant evolution. Multiple infection is predicted to increase the number of mutants at a given infected cell population size, due to a larger number of infection events. We further find that viral complementation can significantly enhance the spread of disadvantageous mutants, but only in select circumstances: it requires the occurrence of direct cell-to-cell transmission through virological synapses, as well as a substantial fitness disadvantage of the mutant, most likely corresponding to defective virus particles. This, however, likely has strong biological consequences because defective viruses can carry genetic diversity that can be incorporated into functional virus genomes via recombination. Through this mechanism, synaptic transmission in HIV might promote virus evolvability.
An improved mode of running PASTA
Authors: Yang Qikai , Warnow Tandy 
Published: September 2020

AbstractPASTA is a method for estimating alignments and trees that has been able to provide excellent accuracy on large sequence datasets. By design, PASTA operates using iteration, in which the tree from the previous iteration is used to inform a divide-and-conquer strategy during which a new alignment is computed on the sequence dataset, and then a new maximum likelihood tree is estimated on the new alignment. In its default setting, PASTA runs for three iterations and returns that alignment/tree pair from the last iteration. Here we use both biological and simulated nucleotide datasets to show that returning the alignment/tree pair that has the best maximum likelihood score improves on the default usage.
Cystic proliferation of embryonic germ stem cells is necessary to reproductive success and normal mating behavior in medaka
Authors: Arias Padilla Luisa F. , Castañeda-Cortés Diana C. , Rosa Ivana F. , Nóbrega Rafael Henrique , Fernandino Juan I. 
Published: September 2020

ABSTRACTThe production of an adequate number of gametes in both sexes is necessary for normal reproduction, for which the regulation of proliferation from early gonadal development to adulthood is key. Cystic proliferation of embryonic stem germ cells prior the onset of gametogenesis is an especially important step prior to the beginning of meiosis. However, in vertebrates, the molecular regulators of cystic proliferation remain unknown. Here, we report thatndrg1b, a member of the N-myc downstream regulated family, is an important regulator of cystic proliferation in medaka. We generated mutants ofndrg1bthat led to a disruption of proliferation type II, independently of the TGF-β signaling pathway. This loss of cystic proliferation was observed from embryogenic to adult stages, impacting the success of gamete production and reproductive parameters such as spawning and fertilization. Interestingly, the depletion of cystic proliferation of thendrg1bmutant also impacted male sexual behavior, with a decrease of mating vigor. These data illustrate why it is also necessary to consider gamete production capacity in order to analyze reproductive behavior.HIGHLIGHTSNdrg1b is involved in the regulation of cystic proliferation in gonad from embryo to adulthood.The cystic proliferation is independently of the TGF-β signaling pathway.Decrease of production of gametes declines reproductive success for both sexes.Reduction of cystic proliferation declines male sexual behavior, with a decrease of mating vigor.
From Face-to-Face to Online Modality: Implications for Undergraduate Learning While the World is Temporarily Closed in the Age of COVID-19
Authors: Hacisalihoglu Gokhan 
Published: September 2020

AbstractThe second half of the Spring 2020 semester has been an unprecedented time globally due to the ongoing coronavirus disease 2019 (COVID-19). COVID-19 pandemic has forced more than one billion students out of school, has disrupted the world and led all university courses switched to online instruction social distancing actions taken to limit the spread of the virus. The aim of the present study is to evaluate the pandemic related changes for undergraduate students, to assess their perspectives related to their learning, experiences in two courses, and to discuss the far-reaching potential implications for the upcoming summer and fall semesters. An electronic survey was conducted to gather data on the student perceptions and learning characteristics of this transition from face-to-face (F2F) to online at a medium-sized university in the Southeast in the Spring 2020 semester. Nearly 88% of the participants indicated that the COVID-19 pandemic impacted their education, while 19% indicated that they prefer online over F2F learning. Furthermore, the online modality significantly increased attendance in General Biology I. Our study also showed that the usage of live conferencing and digital applications increased due to the pandemic. The current research fills the gap in the existing literature by providing the first study on the effects of the ongoing COVID-19 pandemic on undergraduate learning and experiences in the most unique dual modality of the Spring 2020 semester.
Polygenic Scores for Plasticity: A New Tool for Studying Gene-Environment Interplay
Authors: Johnson Rebecca , Sotoudeh Ramina , Conley Dalton 
Published: September 2020

AbstractOutcomes of interest to demographers—fertility; health; education—are the product of both an individual’s genetic makeup and his or her social environment. Yet Gene × Environment research (GxE) currently deploys a limited toolkit on the genetic side to study gene-environment interplay: polygenic scores (PGS, or what we call mPGS) that reflect the influence of genetics on levels of an outcome. The purpose of the present paper is to develop a genetic summary measure better suited for GxE research. We develop what we callvariance polygenic scores(vPGS), or polygenic scores that reflect genetic contributions to plasticity in outcomes. The first part of the analysis uses the UK Biobank (N ~ 326,000 in the training set) and the Health and Retirement Study (HRS) to compare four approaches for constructing polygenic scores for plasticity. The results show that widely-used methods for discovering which genetic variants affect outcome variability fail to serve as distinctive new tools for GxE. Then, using the polygenic scores that do capture distinctive genetic contributions to plasticity, we analyze heterogeneous effects of a UK education reform on health and educational attainment. The results show the properties of a new tool useful for population scientists studying the interplay of nature and nurture and for population-based studies that are releasing polygenic scores to applied researchers.
Loss of mitochondrial protease CLPP activates type I interferon responses through the mtDNA-cGAS-STING signaling axis
Authors: Torres-Odio Sylvia , Lei Yuanjiu , Gispert Suzana , Maletzko Antonia , Key Jana , Menissy Saeed , Wittig Ilka , Auburger Georg , West A. Phillip 
Published: September 2020

AbstractCaseinolytic mitochondrial matrix peptidase proteolytic subunit, CLPP, is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome (PS), but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP null mice remain unclear. Here we report the steady state activation of type I interferon (IFN-I) signaling and antiviral gene expression in CLPP deficient cells and tissues. Depletion of the cyclic GMP-AMP (cGAS)-Stimulator of Interferon Genes (STING) DNA sensing pathway ablates heightened IFN-I responses and abrogates the broad viral resistance phenotype of CLPP null cells. Moreover, we report that CLPP deficiency leads to mitochondrial DNA (mtDNA) instability and packaging alterations. Pharmacological and genetic approaches to deplete mtDNA or inhibit cytosolic release markedly reduce antiviral gene expression, implicating mtDNA stress as the driver of IFN-I signaling in CLPP null mice. Our work places the cGAS-STING-IFN-I innate immune pathway downstream of CLPP and may have implications for understanding myriad human diseases involving CLPP dysregulation.
Label-free Isolation and Single Cell Biophysical Phenotyping Analysis of Primary Cardiomyocytes Using Inertial Microfluidics
Authors: Tavassoli Hossein , Rorimpandey Prunella , Kang Young Chan , Carnell Michael , Brownlee Chris , Pimanda John E , Chan Peggy P.Y. , Chandrakanthan Vashe 
Published: September 2020

AbstractTo advance our understanding of cardiomyocyte identity and function, we need appropriate tools to isolate pure primary cardiomyocytes. We have developed a label-free method to purify viable cardiomyocytes from mouse neonatal hearts using a simple inertial microfluidics biochip. Cardiomyocytes were sorted from neonatal hearts and isolated to >90% purity and their physico-mechanical properties were evaluated using real time deformability cytometry. Purified cardiomyocytes were viable and retained their identity and function as depicted by expression of cardiac specific markers and contractility. Furthermore, we showed that cardiomyocytes have a distinct physico-mechanical phenotype that could be used as an intrinsic biophysical marker to distinguish these cells from other cell types within the heart. Taken together, this cardiomyocyte isolation and phenotyping method could serve as a valuable tool to progress our understanding of cardiomyocyte identity and function, which will ultimately benefit many diagnostic development and cardiac treatment studies.
A Maize Practical Haplotype Graph Leverages Diverse NAM Assemblies
Authors: Franco Jose A. Valdes , Gage Joseph L. , Bradbury Peter J. , Johnson Lynn C. , Miller Zachary R. , Buckler Edward S. , Romay M. Cinta 
Published: September 2020

AbstractAs a result of millions of years of transposon activity, multiple rounds of ancient polyploidization, and large populations that preserve diversity, maize has an extremely structurally diverse genome, evidenced by high-quality genome assemblies that capture substantial levels of both tropical and temperate diversity. We generated a pangenome representation (the Practical Haplotype Graph, PHG) of these assemblies in a database, representing the pangenome haplotype diversity and providing an initial estimate of structural diversity. We leveraged the pangenome to accurately impute haplotypes and genotypes of taxa using various kinds of sequence data, ranging from WGS to extremely-low coverage GBS. We imputed the genotypes of the recombinant inbred lines of the NAM population with over 99% mean accuracy, while unrelated germplasm attained a mean imputation accuracy of 92 or 95% when using GBS or WGS data, respectively. Most of the imputation errors occur in haplotypes within European or tropical germplasm, which have yet to be represented in the maize PHG database. Also, the PHG stores the imputation data in a 30,000-fold more space-efficient manner than a standard genotype file, which is a key improvement when dealing with large scale data.
DARPP-32 Distinguishes a Subset of Adult-Born Neurons in Zebra Finch HVC
Authors: Aronowitz Jake V , Kirn John R , Pytte Carolyn L , Aaron Gloster B 
Published: September 2020

AbstractAdult male zebra finches (Taeniopygia guttata) continually incorporate adult-born neurons into HVC, a telencephalic brain region necessary for the production of learned song. These neurons express immediate early genes during song production, suggesting a role for neurogenesis in song production throughout the lifespan. Half of these adult-born HVC neurons (HVC NNs) can be backfilled from the robust nucleus of the arcopallium (RA) and are a part of the vocal motor pathway underlying learned song production, but the other half do not backfill from RA, and they remain to be characterized. Here we used cell birth-dating, retrograde tract tracing, and immunofluorescence to demonstrate that half of all HVC NNs express thephosphoprotein DARPP-32, a protein associated with dopamine (DA) receptor expression. We also demonstrate that DARPP-32+ HVC NNs are contacted by tyrosine hydroxylase immunoreactive fibers suggesting that they receive catecholaminergic input, have transiently larger nuclei than DARPP-32− HVC NNs, and do not backfill from RA. Taken together, these findings help characterize a group of HVC NNs that have no apparent projections to RA and so far have eluded any positive identification other than HVC NN status.
Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults
Authors: Li Binglan , Veturi Yogasudha , Verma Anurag , Bradford Yuki , Daar Eric S. , Gulick Roy M. , Riddler Sharon A. , Robbins Gregory K. , Lennox Jeffrey L. , Haas David W. , Ritchie Marylyn D. 
Published: September 2020

AbstractAs a type of relatively new methodology, the transcriptome-wide association study (TWAS) has gained interest due to capacity for gene-level association testing. However, the development of TWAS has outpaced statistical evaluation of TWAS gene prioritization performance. Current TWAS methods vary in underlying biological assumptions about tissue specificity of transcriptional regulatory mechanisms. In a previous study from our group, this may have affected whether TWAS methods better identified associations in single tissues versus multiple tissues. We therefore designed simulation analyses to examine how the interplay between particular TWAS methods and tissue specificity of gene expression affects power and type I error rates for gene prioritization. We found that cross-tissue identification of expression quantitative trait loci (eQTLs) improved TWAS power. Single-tissue TWAS (i.e., PrediXcan) had robust power to identify genes expressed in single tissues, but, had high false positive rates for genes that are expressed in multiple tissues. Cross-tissue TWAS (i.e., UTMOST) had overall equal or greater power and controlled type I error rates for genes expressed in multiple tissues. Based on these simulation results, we applied a tissue specificity-aware TWAS (TSA-TWAS) analytic framework to look for gene-based associations with pre-treatment laboratory values from AIDS Clinical Trial Group (ACTG) studies. We replicated several proof-of-concept transcriptionally regulated gene-trait associations, includingUGT1A1(encoding bilirubin uridine diphosphate glucuronosyl transferase enzyme) and total bilirubin levels (p = 3.59×10−12), andCETP(cholesteryl ester transfer protein) with high-density lipoprotein cholesterol (p = 4.49×10−12). We also identified several novel genes associated with metabolic and virologic traits, as well as pleiotropic genes that linked plasma viral load, absolute basophil count, and/or triglyceride levels. By highlighting the advantages of different TWAS methods, our simulation study promotes a tissue specificity-aware TWAS analytic framework that revealed novel aspects of HIV-related traits.publicly available.
Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria
Authors: Yang Rui , Mele Federico , Worley Lisa , Langlais David , Rosain Jérémie , Benhsaien Ibithal , Elarabi Houda , Croft Carys A. , Doisne Jean-Marc , Zhang Peng , Weisshaar Marc , Jarrossay David , Latorre Daniela , Shen Yichao , Han Jing , Gruber Conor , Markle Janet , Al Ali Fatima , Rahman Mahbuba , Khan Taushif , Seeleuthner Yoann , Kerner Gaspard , Husquin Lucas T. , Maclsaac Julia L. , Jeljeli Mohamed , Ailal Fatima , Kobor Michael S. , Oleaga-Quintas Carmen , Roynard Manon , Bourgey Mathieu , El Baghdadi Jamila , Boisson-Dupuis Stéphanie , Puel Anne , Batteux Fréderic , Rozenberg Flore , Marr Nico , Pan-Hammarström Qiang , Bogunovic Dusan , Quintana-Murci Lluis , Carroll Thomas , Ma Cindy S , Abel Laurent , Bousfiha Aziz , Di Santo James P. , Glimcher Laurie H , Gros Philippe , Tangye Stuart G , Sallusto Federica , Bustamante Jacinta , Casanova Jean-Laurent 
Published: September 2020

SummaryInborn errors of human IFN-γ immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to an inherited deficiency of the transcription factor T-bet. This deficiency abolishes the expression of T-bet target genes, includingIFNG, by altering chromatin accessibility and DNA methylation in CD4+T cells. The patient has profoundly diminished counts of mycobacterial-reactive circulating NK, invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2+γδ T lymphocytes, and of non-mycobacterial-reactive classic TH1 lymphocytes, the remainders of which also produce abnormally low amounts of IFN-γ. Other IFN-γ-producing lymphocyte subsets however develop normally, but with low levels of IFN-γ production, with exception of Vδ2−γδ T lymphocytes, which produce normal amounts of IFN-γ in response to non-mycobacterial stimulation, and non-classic TH1 (TH1*) lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of, and IFN-γ production by, innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+γδ T cells), with mycobacterial-specific, IFN-γ-producing, purely adaptive αβ TH1* cells unable to compensate for this deficit.
Mechanical Regulation of Stem Cell Proliferation and Fate Decisions by their Differentiated Daughters
Authors: Ning Wenxiu , Muroyama Andrew , Li Hua , Lechler Terry 
Published: September 2020

AbstractBasal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that serve an essential role in generating the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. These phenotypes were rescued by pharmacological inhibitors of contractility. Live-imaging revealed that increasing the contractility of differentiated cells resulted in stabilization of adherens junctions and impaired movement of basal progenitors during hair placode morphogenesis, as well as a defect in migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions and migration, similar to the known roles of extracellular matrix rigidity. Additionally, this work demonstrates that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.
Corticospinal neurons encode complex motor signals that are broadcast to dichotomous striatal circuits
Authors: Nelson Anders , Abdelmesih Brenda , Costa Rui M 
Published: September 2020

SummarySensorimotor cortex controls movement in part through direct projections to the spinal cord. Here we show that these corticospinal neurons (CSNs) possess axon collaterals that innervate many supraspinal brain regions critical for motor control, most prominently the main input to the basal ganglia, the striatum. Corticospinal neurons that innervate the striatum form more synapses on D1-than D2-striatal projection neurons (SPNs). This biased innervation strategy corresponds to functionally distinct patterns of termination in spinal cord. CSNs are strongly driven during a striatum-dependent sequential forelimb behavior, and often represent high level movement features that are not linearly related to kinematic output. Copies of these activity patterns are relayed in a balanced fashion to both D1 and D2 projection pathways. These results reveal a circuit logic by which motor cortex corticospinal neurons relay both kinematic-related and unrelated signals to distinct striatal and spinal cord pathways, where postsynaptic connectivity ultimately dictates motor specificity.HighlightsCorticospinal neurons send axon collaterals most abundantly to the striatumBiases in striatal innervation correspond to biases in spinal innervationCSNs represent complex movement sequence informationCorollary motor sequence signals are relayed to both striatal projection pathwayseTOC BlurbNelson, A. et al. detail the organization of corticospinal neurons and their coordinated cell type-specific targets in the dorsolateral striatum and spinal cord. Corticospinal neurons encode both kinematic-related and unrelated signals during motor sequences, and relay this information in a balanced fashion to dichotomous striatal pathways.
Role of hemocytes in the regeneration of germline stem cells inDrosophila
Authors: Varga Virginia Beatrix , Szikszai Fanni , Szinyákovics Janka , Manzéger Anna , Puska Gina , Kovács Tibor , Vellai Tibor 
Published: September 2020

AbstractCellular regeneration, which relies on extensive restructuring of cytoplasmic materials, is an essential process to restore tissues and organs lost during aging, degenerative diseases and injury. At early stages ofDrosophilaspermatogenesis, when cellular constituents are intensely remodeled, there are two different populations of stem cells, the somatic stem cells and the germline stem cells (GSCs). GSCs divide by asymmetric division to give rise two distinct daughter cells. One of them will leave the stem cells’ niche and differentiate into spermatogonial cells (SCs). Both aging and cellular stress can lead to the loss of GSCs. Lost GSCs can be restored by dedifferentiation of SCs into functional GSCs. In other tissues, macrophages provide specific conditions for cellular transformation. Here we examined the potential role of immune surveillance cells called hemocytes during dedifferentiation of SGs into GSCs. We found an elevated number of hemocytes during this dedifferentiation process. Immune depletion of hemocytes decreased the regeneration capacity of germline. We also show that autophagy, which plays a pivotal role in cellular differentiation by eliminating unwanted, superfluous parts of the cytoplasm, becomes upregulated in dedifferentiating SCs upon JAK-STAT signaling emitted by hemocytes. Furthermore, these immune cells regulate expression of Omi/HtrA2, a key regulator of apoptosis in early spermatogenesis. Together, we suggest that hemocytes have important functions in the dedifferentiation process of GSCs.