bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers to gene flow play an important role in miantaining reproductive isolation between two closely relatedPopulus(Salicaceae) species
Authors: Tian Yang , Liu Shuyu , Ingvarsson Pär K. , Zhao Dandan , Wang Li , Abuduhamiti Baoerjiang , Wu Zhiqiang , Zhang Jianguo , Wang Zhaoshan 
Published: September 2020

AbstractIn most species, natural selection plays a key role in genomic heterogeneous divergence. Additionally, barriers to gene flow, such as chromosomal rearrangements or gene incompatibilities, can cause genome heterogeneity. We used genome-wide re-sequencing data from 27Populus albaand 28P. adenopodaindividuals to explore the causes of genomic heterogeneous differentiation in these two closely related species. In highly differentiated regions, neutrality tests (Tajima’s D and Fay & Wu’s H) revealed no difference while the absolute divergence (dxy) were significantly higher than genome background, which indicates that natural selection did not play a major role but barriers to gene flow play an important role in generating genomic heterogeneous divergence and reproductive isolation. The two species diverged ∼5-10 million years ago (Mya), when the Qinghai-Tibet Plateau reached a certain height and the inland climate of the Asian continent became arid. We further found some genes that are related to reproduction.
NEON Crowns: a remote sensing derived dataset of 100 million individual tree crowns
Authors: Weinstein Ben. G. , Marconi Sergio , Bohlman Stephanie , Zare Alina , Singh Aditya , Graves Sarah J. , White Ethan 
Published: September 2020

AbstractForests provide essential biodiversity, ecosystem and economic services. Information on individual trees is important for understanding the state of forest ecosystems but obtaining individual-level data at broad scales is challenging due to the costs and logistics of data collection. While advances in remote sensing techniques allow surveys of individual trees at unprecedented extents, there remain significant technical and computational challenges in turning sensor data into tangible information. Using deep learning methods, we produced an open-source dataset of individual-level crown estimates for 100 million trees at 37 sites across the United States surveyed by the National Ecological Observatory Network’s Airborne Observation Platform. Each canopy tree crown is represented by a rectangular bounding box and includes information on the height, crown area, and spatial location of the tree. Tree crowns identified using this technique correspond well with hand-labeled crowns, exhibiting both high levels of overlap and good correspondence in height estimates. These data have the potential to drive significant expansion of individual-level research on trees by facilitating both regional analyses at scales of ~10,000 ha and cross-region comparisons encompassing forest types from most of the United States.
Distinguishing between interaction and dispersion effects in the analysis of gene-environment interaction
Authors: Domingue Benjamin W. , Kanopka Klint , Mallard Travis T. , Trejo Sam , Tucker-Drob Elliot M. 
Published: September 2020

AbstractGenotype-by-environment interaction (GxE) occurs when the size of a genetic effect varies systematically across levels of the environment and when the size of an environmental effect varies systematically across levels of the genotype. However, total variance in the phenotype may shift as a function of the moderator irrespective of its etiology such that theproportionaleffect of the predictor is constant. We expand the traditional GxE regression model to directly account for heteroscedasticity associated with both the genotype and the measured environment. We then derive a test statistic,ξ, for inferring whether GxE can be attributed to an effect of the moderator on the dispersion of the phenotype. We apply this method to identify genotype-by-birth year interactions for Body Mass Index (BMI) that are distinguishable from general secular increases in the variance of BMI or associations of the genetic predictors (both PGS and individual loci) with BMI variance. We provide software for analyzing such models.
S3V2-IDEAS: a package for normalizing, denoising and integrating epigenomic datasets across different cell types
Authors: Xiang Guanjue , Giardine Belinda M. , Mahony Shaun , Zhang Yu , Hardison Ross C 
Published: September 2020

AbstractSummaryEpigenetic modifications reflect key aspects of transcriptional regulation, and many epigenomic data sets have been generated under many biological contexts to provide insights into regulatory processes. However, the technical noise in epigenomic data sets and the many dimensions (features) examined make it challenging to effectively extract biologically meaningful inferences from these data sets. We developed a package that reduces noise while normalizing the epigenomic data by a novel normalization method, followed by integrative dimensional reduction by learning and assigning epigenetic states. This package, called S3V2-IDEAS, can be used to identify epigenetic states for multiple features, or identify signal intensity states and a master peak list across different cell types for a single feature. We illustrate the outputs and performance of S3V2-IDEAS using 137 epigenomics data sets from the VISION project that providesValIdatedSystematicIntegratiONof epigenomic data in hematopoiesis.Availability and implementationS3V2-IDEAS pipeline is freely available as open source software released under an MIT license at:https://github.com/guanjue/S3V2_IDEAS_ESMPContactrch8@psu.edu,gzx103@psu.eduSupplementary informationS3V2-IDEAS-bioinfo-supplementary-materials.pdf
ETV5 expression positively correlates with promoter methylation and predicts response for 5-FU-based adjuvant therapy response in proximal colon cancer
Authors: Giri Anil K 
Published: September 2020

AbstractDiscovery of markers predictive for 5-Fluorouracil (5-FU)-based adjuvant chemotherapy (adjCTX) response in patients with locally advanced stage II and III colorectal cancer (CRC) is necessary for early identification of potential responders as only 20-65% of CRC patients benefit from the treatment. PEA3 subfamily of ETS transcription factors (ETV1, ETV4, and ETV5) are upregulated in multiple cancers including colon cancers. However, the underlying epigenetic mechanism regulating their overexpression and their role in predicting therapy response in colon cancer is largely unexplored. In this study, using gene expression and methylation data from The Cancer Genome Atlas (TCGA) project, we showed that promoter DNA methylation negatively correlates with ETV4 expression (ρ= -0.17, p=5.6×10−3) and positively correlates with ETV5 expression (ρ= 0.22, p=1.43×10−4) in colon cancer tissue. Further, our analysis in 662 colon cancer patients treated with 5-FU-based-adjCTX revealed that higher ETV5 expression associated with shorter relapse-free survival (RFS) of treated patients with proximal tumors (Hazard ratio = 3.30 - 6.22, p=0.005-0.02). We also observed higher expression of signaling molecules involved in cellular proliferation (e.g. GNB5, DUSP4, FYN) in patients with high ETV5 level, suggesting that the increased cellular proliferation due to overexpression of these genes could drive the therapy resistance. The present study suggests ETV5 expression as a strong predictive biomarker for 5-FU-based adjCTX response in stage II/III CRC patients with proximal tumors.
Evidence for conformational change-induced hydrolysis of β-tubulin-GTP
Authors: Paydar Mohammadjavad , Kwok Benjamin H. 
Published: September 2020

ABSTRACTMicrotubules, protein polymers of α/β-tubulin dimers, form the structural framework for many essential cellular processes including cell shape formation, intracellular transport, and segregation of chromosomes during cell division. It is known that tubulin-GTP hydrolysis is closely associated with microtubule polymerization dynamics. However, the precise roles of GTP hydrolysis in tubulin polymerization and microtubule depolymerization, and how it is initiated are still not clearly defined. We report here that tubulin-GTP hydrolysis can be triggered by conformational change induced by the depolymerizing kinesin-13 proteins or by the stabilizing chemical agent paclitaxel. We provide biochemical evidence that conformational change precedes tubulin-GTP hydrolysis, confirming this process is mechanically driven and structurally directional. Furthermore, we quantitatively measure the average size of the presumptive stabilizing “GTP cap” at growing microtubule ends. Together, our findings provide the molecular basis for tubulin-GTP hydrolysis and its role in microtubule polymerization and depolymerization.
Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties
Authors: Kia Danial Sharifi , Shen Yuanjun , Bachman Timothy N. , Goncharova Elena A. , Kim Kang , Simon Marc A. 
Published: September 2020

AbstractHealthy aging has been associated with alterations in pulmonary vasculature and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative histological analysis were employed to study two groups of Sprague-Dawley rats: control (11 weeks) and aging (80 weeks).Aging was associated with increases in RV peak pressures (≈↑17%, p=0.017), RV contractility (≈↑52%, p= 0.004), and RV wall thickness (≈↑34%, p=0.002). Longitudinal realignment of RV collagen (16.4°, p=0.013) and myofibers (14.6°, p=0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. A bimodal alteration in biomechanical properties was noted, resulting in increased myofiber stiffness (≈↑158%, p=0.0006) and decreased effective collagen fiber stiffness (≈↓67%, p=0.031).Our results demonstrate the potential of healthy aging to modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fiber reorientation, and altered collagen/myofiber stiffness. Some similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload.
Optogenetic activation of CA1 pyramidal neuronsin vivoinduces hypersynchronous and low voltage fast seizures
Authors: Huynh Trong D , Ashraf Omar , Craig Hayden , Larmeu Lana , Barker Benjemin , Stephenson Cade , Murcia Derrick , Howard Brady , Sun Hai 
Published: September 2020

ABSTRACTIncreasing evidence supports the idea that the CA1 of the hippocampus plays an important role in the pathogenesis of temporal lobe epilepsy (TLE). There is however a lack of proof that the over-excitation of CA1 alone is sufficient in inducing seizuresin vivo. Furthermore, the relevance of the seizures induced from the over-excitation of CA1 to the pathophysiology of TLE is undetermined. Here, we employed optogenetics to activate pyramidal neurons (PNs) in CA1, which reliably induced generalized seizures in freely moving non-epileptic mice. We showed that repeated photostimulations had a kindling effect. In addition, seizures induced by over-active CA1 PNs were dominated by two distinctive onset patterns, i.e. hypersynchronous (HYP) and low voltage fast (LVF) activities, which are widely recorded in patients with and animal models of TLE. In our study, HYP seizures were predominantly associated with the first photostimulation and were entirely replaced by the LVF type afterwards. This phenomenon suggests that the activation of CA1 PNs, when occurring after the first seizure, could lead to the recruitment of GABAergic interneurons to participate in the seizure generation. These findings suggest that seizures induced from the over-excitation of CA1 PNs likely involved the same hippocampal networks and cellular mechanisms underlying TLE.
Glypican4 mediates Wnt transport between germ layers via signaling filopodia
Authors: Hu Bo , Balaraju Anurag Kakkerla , Rodriguez Juan J , Gao Yuanyuan , Nguyen Nhan T , Steen Heston , Suhaib Saeb , Chen Songhai , Lin Fang 
Published: September 2020

AbstractGlypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here we show that transgenic expression of GFP-Gpc4 in the endoderm ofgpc4mutants rescues C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2, and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound Wnt5b and regulated formation of the filopodia that transport Wnt5b to neighboring cells. Blocking signaling filopodia that extend from endodermal cells suppressed this rescue. Thus, endodermal signaling filopodia that expressed GFP-Gpc4 transported Wnt5b, and likely Wnt11f2, to other germ layers, rescuing the C&E defects caused by agpc4deficiency. Our study reveals a new mechanism that could explainin vivomorphogen distribution involving Gpc4.
L-ascorbic acid (vitamin C) fermentation by the human pathogenVibrio cholerae
Authors: Rosenberger J.R. , McDonald N.D. , Boyd E.F. 
Published: September 2020

AbstractL-ascorbic acid, commonly known as vitamin C, is a ubiquitous 6-carbon carbohydrate characterized by its ability to scavenge free radicals. In enteric bacteria, L-ascorbate can be utilized as a nutrient using the UlaABCDEF and UlaG-UlaRpathway under anaerobic conditions. In this study, we identified homologs of the Ula system withinVibrio choleraeand showed thatV. choleraeis able to utilize L-ascorbate as an energy source. Growth pattern assays of aulaGin-frame deletion mutant demonstrated thatulaGis essential for L-ascorbate fermentation. Expression analysis showed thatulacatabolism and transport genes were significantly induced in cells grown in the presence of L-ascorbate compared to glucose and these genes were also highly induced during growth on intestinal mucus. Inin vitrogrowth competition assays, theulaGmutant was outcompeted by wild type when grown in intestinal mucus suggesting the Ula system could be important for fitness. Within theulaoperon inV. choleraeand allVibriospecies a homology of ORF VCA0243 is present that encodes a pyridoxal phosphate (PLP) phosphatase. This enzyme inE. coli, converts the active form of vitamin B6PLP to its inactive form pyridoxal (PL). InV. splendidusand related species, the aerobic and anaerobic L-ascorbate pathway genes cluster together and both systems contain a PLP phosphatase. An in-frame deletion mutant ofvca0243resulted in a growth defect in L-ascorbate fermentation as well as additional carbon and amino acid sources indicating a role in cellular metabolism. Phylogenetic analysis of UlaG and UlaD suggested the region was acquired by horizontal gene transfer.ImportanceL-ascorbate is a carbohydrate present in the human intestine, available for microbial consumption and several enteric species have been shown to utilize this compound as an energy source. We demonstrated that L-ascorbate fermentation genes are also present among marine bacteria from the familyVibrionaceaeand that the human pathogenV. choleraecan ferment L-ascorbate as an energy source. Within the Ula operon in allVibrionaceae, a putative pyridoxal phosphate phosphatase was present that was required for L-ascorbate fermentation and cellular metabolism in general. The Ula system was present among a limited number of genera withinVibrionaceae; Vibrio, AliivibrioandPhotobacteriumand showed an evolutionary history consistent with horizontal transfer between genera and species.
Is There a Correlation Between Pulmonary Inflammation Index With COVID-19 Disease Severity And Outcome?
Authors: Hussein Aliae AR Mohamed , Galal Islam , Mohammed Mohammed M , Abd Elaal Howida K , Aly Karim 
Published: September 2020

AbstractRationalthe radiologic pulmonary inflammatory index (PII) may be used as early predictor of inflammation as laboratory assessments in COVID-19 cases. The purpose of this study was to compare the clinical and radiological features between the cases of COVID-19 necessitating admittance to the intensive care unit (ICU) and those who did not, and to correlate the radiological pulmonary inflammation index (PII) with other inflammatory markers and outcome.Patients and methodsThis study included 72 patients consecutively admitted with confirmed COVID-19. Their electronic records of were retrospectively revised and the demographic, clinical, laboratory (complete blood count, C reactive protein, D dimer and serum ferritin), HRCT data, pulmonary inflammation index (PII) and the outcomes of the patients (ICU admission, death, recovery, and referral) were analyzed.ResultsThey were 50/50% males/females, mean age was 47.1 ± 16.8 (median 47 years). During their stay, 15.3% necessitated ICU admittance, 49 (68%) cured and discharged, 9 cases referred and five cases (6.9%) died. The baseline lesions identified were ground glass opacification recognized in (93%), higher PII and >3 lobes affection were considerably recorded in those who required ICU admittance (P= 0.041 and 0.013). There were moderate positive correlations between PII with age (r=0.264, P=0.031) and other prognostic inflammatory indicators as ferritin (r=0.225, P=0.048), D Dimer (r=0.271, P=0.043) and serum creatinine.ConclusionsThe use of PII together with clinical and laboratory data may be valuable in defining the inflammatory state of COVID-19. It was correlated with other inflammatory indices as D dimer, ferritin even before clinical deterioration. This may allow clinicians to avoid the progression of the illness and improve cure rates by proper early intervention.
Emotional tagging retroactively promotes memory integration through rapid neural reactivation and reorganization
Authors: Zhu Yannan , Zhang Lingke , Zeng Yimeng , Chen Changming , Fernández Guillén , Qin Shaozheng 
Published: September 2020

AbstractNeutral events preceding emotional experiences are thought to be better remembered by tagging them as significant to simulate future event predictions. Yet, the neurobiological mechanisms how emotion transforms initially mundane events into strong memories remain unclear. By two behavioral and one fMRI studies with adapted sensory preconditioning paradigm, we show rapid neural reactivation and reorganization underlying emotion-tagged retroactive memory enhancement. Behaviorally, emotional tagging enhanced initial memory for neutral associations across the three studies. Neurally, emotional tagging potentiated reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. Moreover, it induced large-scale hippocampal-neocortical reorganization supporting such retroactive benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during online processing, and a shift from stimulus-relevant neocortex to transmodal prefrontal-parietal areas during offline post-tagging rest. Together, emotional tagging retroactively promotes associations between past neutral events through stimulating rapid reactivation of overlapping representations and reorganizing related memories into an integrated network.
Structural basis for binding mechanism of human serum albumin complexed with cyclic peptide dalbavancin
Authors: Ito Sho , Senoo Akinobu , Nagatoishi Satoru , Ohue Masahito , Yamamoto Masaki , Tsumoto Kouhei , Wakui Naoki 
Published: September 2020

ABSTRACTCyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life), is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. SAXS and ITC experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of non-covalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA.
Enhanced SARS-CoV-2 Neutralization by Secretory IgA in vitro
Authors: Wang Zijun , Lorenzi Julio C. C. , Muecksch Frauke , Finkin Shlomo , Viant Charlotte , Gaebler Christian , Cipolla Melissa , Hoffman Hans-Heinrich , Oliveira Thiago Y. , Oren Deena A. , Ramos Victor , Nogueira Lilian , Michailidis Eleftherios , Robbiani Davide F. , Gazumyan Anna , Rice Charles M. , Hatziioannou Theodora , Bieniasz Paul D. , Caskey Marina , Nussenzweig Michel C. 
Published: September 2020

AbstractSARS-CoV-2 primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of the illness. Although potent IgG antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might impact the initial viral spread and transmissibility from the mucosa. Here we characterize the IgA response to SARS-CoV-2 in a cohort of 149 individuals. IgA responses in plasma generally correlate with IgG responses and clones of IgM, IgG and IgA producing B cells that are derived from common progenitors are evident. Plasma IgA monomers are 2-fold less potent than IgG equivalents. However, IgA dimers, the primary form in the nasopharynx, are on average 15 times more potent than IgA monomers. Thus, secretory IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.
Dissecting the heterogeneous subcortical brain volume of Autism spectrum disorder (ASD) using community detection
Authors: Li Ting , Hoogman Martine , Mota Nina Roth , Buitelaar Jan K. ,   the ENIGMA-ASD Working Group, Vasquez Alejandro Arias , Franke Barbara , van Rooij Daan 
Published: September 2020

AbstractStructural brain alterations found in Autism Spectrum Disorder (ASD) have previously been very heterogeneous, with overall limited effect sizes for every region implicated. In this study, we aimed at exploring the existence of subgroups in ASD, based on neuroanatomic profiles; we hypothesized that effect sizes of case/control difference would be increased in defined subgroups. Using the dataset from the ENIGMA-ASD Working Group (n=2661), exploratory factor analysis (EFA) was applied on seven subcortical volumes of individuals with ASD and controls to uncover the underlying organization of subcortical structures. Based on earlier findings in ADHD patients and controls as well as data availability, we focused on three age groups: boys (aged 4-14 years), male adolescents (aged 14-22 years), and adult men (aged >=22 years). The resulting factor scores were used in a community detection (CD) analysis, to cluster participants into subgroups. Three factors were found in each sample, with the factor structure in adult men differing from that in boys and male adolescents. From the patterns in these factors, CD uncovered four distinct communities in boys and three communities in adolescents and adult men, irrespective of ASD diagnostic status. The effect sizes of case/control comparisons appeared more pronounced than in the whole sample in some communities. Based on subcortical volumes, we succeeded in stratifying our participants into more homogeneous subgroups with similar brain structural patterns. The stratification enhanced our ability to observe case/control differences of subcortical brain volumes in ASD, and may help explain some of the heterogeneity of previous findings in ASD.