bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal blood and amnionic oxytocin receptor gene expression and serum oxytocin levels in preterm birth: a case control study
Authors: Anukriti Kumari , Guleria Kiran , Tyagi Vipin , Suneja Amita , Banerjee B D 
Published: July 2020

ABSTRACTBackgroundThe oxytocin (OXT)-oxytocin receptor (OXTR) system provides promising candidate gene for studies of genetic contributions to prematurity.ObjectiveQuantification and comparison of oxytocin receptor (OXTR) gene expression and serum OXT levels in the blood and amnion of women delivering preterm and evaluation of the correlation between OXTR gene expression in blood and amnion with serum OXT levels in them.Methods70 pregnant women in spontaneous labor delivering vaginally preterm i.e < 37 weeks and equal number of matched controls delivering spontaneously at term (37-42 weeks) were recruited. Maternal serum OXT levels taken in active stage of labor i.e 4 cm cervical dilatation were quantified by ELISA. Gene expression studies in the maternal blood and amnion were done by using real time quantitative polymerase chain reaction (RT-qPCR).ResultsThe mean serum OXT level in PTL was 48.56 ± 6.97 pg/ml; significantly higher than in controls (43.00 ± 3.96 pg/ml), p<0.001. OXTR gene expression both in maternal blood (2.5 times) and amnion (3.5 times) were significantly higher in PTL. A significant positive correlation was observed between serum OXT levels and OXTR gene expression in amnion (r = −0.190, p = 0.025).ConclusionsThe serum OXT levels and OXTR gene expression in amnion surge significantly in active phase of PTL. Thus, amnion probably links OXT-PTGs autocrine paracrine circuit to facilitate PTL. Future studies are needed to devise better OXTR receptor antagonists preferably acting on amnionic OXTRs to prevent PTL.
High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients
Authors: Song Xiang , Hu Wei , Yu Haibo , Zhao Laura , Zhao Yeqian , Zhao Yong 
Published: July 2020

AbstractAngiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects host cells, causing the development of the new coronavirus infectious disease (COVID-19). To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+T, CD8+T, activated CD4+T, activated CD8+T, CD4+CD25+CD127low/−regulatory T cells (Tregs), Th17 cells, NKT cells, B cells, NK cells, monocytes, dendritic cells (DCs), and granulocytes. Additionally, there was no ACE2 expression (< 1%) found on platelets. Compared with interleukin-4-treated type 2 macrophages (M2), the ACE2 expression was markedly increased on the activated type 1 macrophages (M1) after the stimulation with lipopolysaccharide (LPS). Immunohistochemistry demonstrated that high expressions of ACE2 were colocalized with tissue macrophages, such as alveolar macrophages found within the lungs and Kupffer cells within livers of mice. Flow cytometry confirmed the very low level of ACE2 expression on human primary pulmonary alveolar epithelial cells. These data indicate that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.
Deep learning neural network prediction method improves proteome profiling of vascular sap of grapevines during Pierce’s disease development
Authors: Sagawa Cíntia H. D. , Zaini Paulo A. , Assis Renata de A. B. , Saxe Houston , Salemi Michelle , Jacobson Aaron , Phinney Brett S. , Dandekar Abhaya M. 
Published: July 2020

AbstractPlant secretome studies have shown the importance of plant defense proteins in the vascular system against pathogens. Studies on Pierce’s disease of grapevines caused by the xylem-limited bacteriaXylella fastidiosa(Xf) have detected proteins and pathways associated to its pathobiology. Despite the biological importance of the secreted proteins in the extracellular space to plant survival and development, proteome studies are scarce due to technical and technological challenges. Deep learning neural network prediction methods can provide powerful tools for improving proteome profiling by data-independent acquisition (DIA). We aimed to explore the potential of this strategy by combining it within silicospectral library prediction tool, Prosit, to analyze the proteome of vascular leaf sap of grapevines with Pierce’s disease. The results demonstrate that the combination of DIA and Prosit increased the total number of identified proteins from 145 to 360 for grapevines and 18 to 90 forXf. The new proteins increased the range of molecular weight, assisted on the identification of more exclusive peptides per protein, and increased the identification of low abundance proteins. These increases allowed the identification of new functional pathways associated with cellular responses to oxidative stress to be further investigated.
Dynamic regulatory module networks for inference of cell type-specific transcriptional networks
Authors: Siahpirani Alireza Fotuhi , Knaack Sara , Chasman Deborah , Seirup Morten , Sridharan Rupa , Stewart Ron , Thomson James , Roy Sushmita 
Published: July 2020

AbstractMulti-omic datasets with parallel transcriptomic and epigenomic measurements across time or cell types are becoming increasingly common. However, integrating these data to infer regulatory network dynamics is a major challenge. We present Dynamic Regulatory Module Networks (DRMNs), a novel approach that uses multi-task learning to infer cell type-specific cis-regulatory networks dynamics. Compared to existing approaches, DRMN integrates expression, chromatin state and accessibility, accurately predicts cis-regulators of context-specific expression and models network dynamics across linearly and hierarchically related contexts. We apply DRMN to three dynamic processes of different experimental designs and predict known and novel regulators driving cell type-specific expression patterns.
Proprioceptive afferents differentially contribute to effortful perception of object heaviness and mass distribution
Authors: Mangalam Madhur , Desai Nisarg , Singh Tarkeshwar 
Published: July 2020

AbstractWhen humans handle a tool, such as a tennis racket or hammer, for the first time, they often wield it to determine its inertial properties, however, the mechanisms that contribute to perception of inertial properties are not fully understood. The goal of the present study was to investigate how proprioceptive afferents contribute to effortful perception of heaviness and mass distribution of a manually wielded object in the absence of vision. Blindfolded participants manually wielded a set of specially-designed experimental objects of different mass and mass distribution about the wrist at different wrist angles and wrist angular kinematics. By independently manipulating these variables, we aimed to elicit different levels of tonic and rhythmic activity in the muscle spindles of the wrist flexors and extensors and relate them to reported perceptual judgments of heaviness and length. Perception of heaviness and length were predominantly dependent on an object’s static moment and the moment of inertia, respectively. Manipulations of wrist angle and wrist angular kinematics affected perceptual judgments of heaviness and length in relatively opposite ways. As for wrist angle, ulnar deviation consistently resulted in an object being perceived heavier but shorter. Compared to static holding, wielding the object resulted in it being perceived heavier but wielding did not affect perceived length. These results suggest that proprioceptive afferents differentially contribute to effortful perception of object heaviness and mass distribution.
Reproductive effort of intertidal tropical seagrass as an indicator of habitat disturbance
Authors: Mishra Amrit Kumar , Apte Deepak 
Published: July 2020

AbstractHabitat disturbance is one of the major causes of seagrass loss around the Andaman Sea in the Indian Ocean bioregion. Assessing the seagrass response to these disturbances is of utmost importance in planning effective conservation measures. Here we report about seagrass reproductive effort (RE) as an indicator to assess seagrass response to habitat disturbances. Quadrat sampling was used to collect seagrass samples at three locations (a disturbed and undisturbed site per location) of the Andaman and Nicobar Islands. The health of seagrass meadows was quantified based on density-biomass indices of the disturbed sites. A change ratio (D/U) was derived by contrasting the RE of disturbed (D) sites with the undisturbed (U) sites of all three locations. The relationship between RE and plant morphometrics were also quantified. Reproductive density of T.hemprichiiwas higher and significant at the three disturbed sites. The average reproductive density ofT. hemprichiiat the disturbed sites was 3.3-fold higher than the undisturbed sites. The reproductive density consisted around 52% of the total shoot density ofT. hemprichiiat the disturbed sites. In general, the increase in the plant RE was site-specific and was 4-fold higher at the three disturbed sites. Positive and significant correlations was observed between the change ratio of RE and the plant morphometrics, suggesting an active participation of seagrass morphometrics in the reproductive process. Increase in seagrass RE can contribute to the increase in population genetic diversity, meadow maintenance and various ecosystem functions under the influence of anthropogenic disturbance scenarios.
Exome-wide association studies in general and long-lived populations identify genetic variants related to human age
Authors: Sin-Chan Patrick , Gosalia Nehal , Gao Chuan , Van Hout Cristopher V. , Ye Bin , Marcketta Anthony , Li Alexander H. , O’Dushlaine Colm , Li Dadong , Overton John D. , Reid Jeffrey D. , Baras Aris ,   Regeneron Genetics Center, Carey David J. , Ledbetter David H. , Rader Daniel , Ritchie Marylyn D. , Damrauer Scott M. , Milman Sofiya , Barzilai Nir , Glass David J. , Economides Aris N. , Shuldiner Alan R. 
Published: July 2020

SUMMARYAging is characterized by degeneration in cellular and organismal functions leading to increased disease susceptibility and death. Although our understanding of aging biology in model systems has increased dramatically, large-scale sequencing studies to understand human aging are now just beginning. We applied exome sequencing and association analyses (ExWAS) to identify age-related variants on 58,470 participants of the DiscovEHR cohort. Linear Mixed Model regression analyses of age at last encounter revealed variants in genes known to be linked with clonal hematopoiesis of indeterminate potential, which are associated with myelodysplastic syndromes, as top signals in our analysis, suggestive of age-related somatic mutation accumulation in hematopoietic cells despite patients lacking clinical diagnoses. In addition toAPOE, we identified rareDISP2rs183775254 (p = 7.40×10−10) andZYG11Ars74227999 (p = 2.50×10−08) variants that were negatively associated with age in either both sexes combined and females, respectively, which were replicated with directional consistency in two independent cohorts. Epigenetic mapping showed these variants are located within cell-type-specific enhancers, suggestive of important transcriptional regulatory functions. To discover variants associated with extreme age, we performed exome-sequencing on persons of Ashkenazi Jewish descent ascertained for extensive lifespans. Case-Control analyses in 525 Ashkenazi Jews cases (Males ≥ 92 years, Females ≥ 95years) were compared to 482 controls. Our results showed variants inAPOE(rs429358, rs6857), andTMTC2(rs7976168) passed Bonferroni-adjusted p-value, as well as several nominally-associated population-specific variants. Collectively, our Age-ExWAS, the largest performed to date, confirmed and identified previously unreported candidate variants associated with human age.
Protein homeostasis imprinting across evolution
Authors: Koutsandreas Thodoris , Felden Brice , Chevet Eric , Chatziioannou Aristotelis 
Published: July 2020

AbstractProtein homeostasis (a.k.a. proteostasis) is associated with the primary functions of life, and therefore with evolution. However, it is unclear how the cellular proteostasis machines have evolved to adjust the protein biogenesis needs to environmental constraints. Herein, we describe a novel computational approach, based on semantic network analysis, to evaluate proteostasis differentiation during evolution. We show that the molecular components of the proteostasis network (PN) are reliable metrics to deconvolute the life forms into Archaea, Bacteria and Eukarya and to assess the evolution rates among species. Topological properties of semantic graphs were used as new criteria to evaluate PN complexity of 93 Eukarya, 250 Bacteria and 62 Archaea, thus representing a novel strategy for taxonomic classification. This functional analysis provides information about species divergence and pointed towards taxonomic clades that evolved faster than others. Kingdom-specific PN were identified, suggesting that PN complexity correlates evolution. Through the analysis of gene conservation, we found that the gains or losses that occurred throughout PN evolution revealed a dichotomy within both the PN conserved modules and within kingdom-specific modules. Since the PN is implicated in cell fitness, aging and disease onset, it could be used as a new metric to tackle mechanisms underlying ‘gain-of-functions’, and their biological ramifications.
Carotenogenesis ofStaphylococcus aureus: new insights and impact on membrane biophysical properties
Authors: López Gerson-Dirceu , Suesca Elizabeth , Álvarez-Rivera Gerardo , Rosato Adriana , Ibáñez Elena , Cifuentes Alejandro , Leidy Chad , Carazzone Chiara 
Published: July 2020

AbstractStaphyloxanthin (STX) is a saccharolipid derived from a carotenoid inStaphylococcus aureusinvolved in oxidative-stress tolerance and antimicrobial peptide resistance. In this work, a targeted metabolomics and biophysical study was carried out on native and knock-outS. aureusstrains to investigate the biosynthetic pathways of STX and related carotenoids. Identification of 34 metabolites at different growth phases (8, 24 and 48h), reveal shifts of carotenoid populations during progression towards stationary phase. Six of the carotenoids in the STX biosynthetic pathway and three menaquinones (Vitamin K2) were identified in the same chromatogram. Furthermore, other STX homologues with varying acyl chain structures reported herein for the first time, which reveal the extensive enzymatic activity of CrtO/CrtN. Fourier Transform infrared spectroscopy show that STX increases acyl chain order and shifts the cooperative melting of the membrane indicating a more rigid lipid bilayer. This study shows the diversity of carotenoids inS. aureus, and their influence on membrane biophysical properties.
A Whole Blood Thrombus Mimic: Constitutive Behavior Under Simple Shear
Authors: Sugerman Gabriella P. , Kakaletsis Sotirios , Thakkar Parin , Chokshi Armaan , Parekh Sapun H. , Rausch Manuel K. 
Published: July 2020

ABSTRACTDeep vein thrombosis and pulmonary embolism affect 300,000-600,000 patients each year in the US. The progression from deep vein thrombus to pulmonary embolism occurs when blood clots, as a whole or partially, break off from the deep veins and eventually occlude the pulmonary arteries. Venous thromboembolism is the cause of up to 100,000 deaths per year in the US alone. To date, we don’t fully understand this mechanical process among other reasons because in-vivo samples are difficult to obtain, highly heterogeneous, and their shapes are inappropriate for most mechanical tests. Toward overcoming these obstacles, we have set out to develop an in-vitro thrombus mimic and to test this mimic under large deformation simple shear. In addition to reporting on the mechanics of our mimics under simple shear, we explore the sensitivity of their mechanics to coagulation conditions and blood storage time, and compare three hyperelastic material models for their ability to fit our data. We found that thrombus mimics made from whole blood demonstrate strain-stiffening, a negative Poynting effect, and hysteresis when tested quasi-statically to 50% strain under simple shear. Additionally, we found that the stiffness of these mimics does not significantly vary with coagulation conditions or blood storage times. Of the three hyperelastic constitutive models that we tested, the Ogden model provided the best fits to both shear stress and normal stress. In conclusion, we developed a robust protocol to generate regularly-shaped, homogeneous thrombus mimics that lend themselves to simple shear testing under large deformation. Future studies will extend our model to include the effect of maturation and explore its fracture properties toward a better understanding of embolization.
Evidence for a system in the auditory periphery that may contribute to linking sounds and images in space
Authors: Murphy David LK , King Cynthia D , Lovich Stephanie N , Landrum Rachel E , Shera Christopher A , Groh Jennifer M 
Published: July 2020

AbstractEye movements alter the relationship between the visual and auditory spatial scenes. Signals related to eye movements affect the brain’s auditory pathways from the ear through auditory cortex and beyond, but how these signals might contribute to computing the locations of sounds with respect to the visual scene is poorly understood. Here, we evaluated the information contained in the signals observed at the earliest processing stage, eye movement-related eardrum oscillations (EMREOs). We report that human EMREOs carry information about both horizontal and vertical eye displacement as well as initial/final eye position. We conclude that all of the information necessary to contribute to a suitable coordinate transformation of auditory spatial cues into a common reference frame with visual information is present in this signal. We hypothesize that the underlying mechanism causing EMREOs could impose a transfer function on any incoming sound signal, which could permit subsequent processing stages to compute the positions of sounds in relation to the visual scene.
Genome scans of dog behavior implicate a gene network underlying psychopathology in mammals, including humans
Authors: Zapata Isain , Hecht Erin E. , Serpell James A. , Alvarez Carlos E. 
Published: July 2020

AbstractGenetic studies show a general factor associated with all human psychopathology and strongly correlated with personality and intelligence, but its basis is unknown. We performed genome scans of 17 normal and problem behaviors in three multi-breed dog cohorts. 21 of 90 mapped loci were supported for the same, or a related, trait in a second cohort. Several of those loci were also associated with brain structure differences across breeds; and six of the respective top-candidate genes are also associated with human brain structure and function. More broadly, the geneset of canine behavioral scans is supported by enrichment for genes mapped for human behavior, personality, cognition, psychopathology and brain structure. The biology implicated includes, neurogenesis, axon guidance, angiogenesis, brain structure, alternative splicing, disease association, Hox-family transcription factors, and subiculum expression. Because body size and behavior are correlated in dogs, we isolated the effect of body size in the dog mapping and in the comparative human UK Biobank analyses. Our dog findings are consistent with pleiotropy of diverse brain traits with energy metabolism and growth, and suggest behavioral variations often affect neurogenesis. There is support for such pleiotropy in humans and well-powered genetic studies of human psychiatric traits consistently implicate neurogenesis. We propose a genetic network which underlies neuron birth and development throughout life is associated with evolutionary adaptation of behavior and the general psychopathology factor. This understanding has implications for genetic and environmental contributions to psychiatric disease. We discuss how canine translational models can further accelerate the study of psychopathology.Author summaryWe genetically mapped diverse normal and problem behaviors in dogs. The well-established approach we used is ideally suited for finding variation that is common across dog breeds and for pin-pointing the most likely gene candidates. Our analysis of the genes implicated at 90 genome regions shows they are enriched for i) genes mapped for diverse brain functions and pathologies in humans; ii) genes involved in brain development throughout life; and iii) footprints of evolution in dogs, humans and other animals. We propose that is consistent with evolutionary conservation of the general genetic factor of mental health in humans, which is correlated with personality and intelligence. The implications are that this super-network of genes is preferentially targeted by evolutionary adaptation for behavior and that its dysregulation increases risk of mental health disorders.
How to characterize a strain? The neglected influence of clonal heterogeneity on the phenotypes of industrialSaccharomyces
Authors: Rácz Hanna Viktória , Mukhtar Fezan , Imre Alexandra , Rádai Zoltán , Gombert Andreas Károly , Rátonyi Tamás , Nagy János , Pócsi István , Pfliegler Walter P. 
Published: July 2020

AbstractPopulations of microbes are constantly evolving heterogeneity that selection acts upon, yet heterogeneity is non-trivial to assess methodologically. The practice of isolating single cell colonies for establishing, transferring, and using a strain results in single-cell bottlenecks with a generally neglected effect on the characteristics of the strain. We used six industrial yeasts to assess the level of heterogeneity in clonal populations, especially in terms of stress tolerance. First, we uncovered the existence of genome structure variants in available sequenced genomes of clonal lineages of thes strains. Subsequent phenotyping of strains and their newly isolated subclones showed that single-cell bottlenecks during isolation can considerably influence the observable phenotype. Next, we decoupled fitness distributions on the level of individual cells from clonal interference by plating single cell colonies. We used the obtained data on colony area for statistical modeling of the heterogeneity in phenotypes. One strain was further used to show how individual subclonal lineages are remarkably different not just in phenotype, but also in the level of heterogeneity. Thereby we call attention to the fact that choosing an initial clonal lineage from an industrial yeast strain may vastly influence downstream performances and observations on geno- and phenotype, and also on heterogeneity.