bluuebunny/crossref_metadata_2025_split huggingface dataset:
YBX2 Dysregulation in Maturation Arrest NOA YBX2 Dysregulation is a Potential Cause for Late Maturation Arrest in Men with Non-Obstructive Azoospermia
Authors: Flannigan Ryan , Mielnik Anna , Robinson Brian D. , Khani Francesca , Bolyakov Alex , Schlegel Peter N. , Paduch Darius A 
Published: July 2018

AbstractIntroductionYBX2 protein binds to Y-box promotors and to mRNAs in the cytoplasm of pachytene spermatocytes and round spermatids in rodents. Knock-out of YBX2 leads to maturation arrest in animal models. YBX2 binds PRM1 and 2 mRNA, which is transcribed early and sequestrated for translation during late spermatogenesis.ObjectiveThis study aimed to determine if the loss of YBX2 is associated with MA arrest due to the loss of sequestration of protamines in the human testis. As a second aim, we examined the expression of YBX2, and its transcription factors in maturation arrest (MA)(early and late) and normal controls in men.MethodsRNAseq was performed using RNA extracted from human testis samples from 44 men with non-obstructive azoospermia and ten from healthy controls. Differential expression was performed using JMPgenomics, FDR<0.001. FANTOM5 was used to predict enhancers and inhibitors of YBX2 expression. Immunofluorescence (IF) was used to stain testis tissue sections with antibodies against YBX2, SYCP3, and PRM2 in normal and MA samples. Flow cytometry was utilized to characterize YBX2 positive cells.ResultsExpression ofYBX2mRNA was significantly downregulated in early and late MA compared to controls. Surprisingly, PRM1&2 mRNAs were also depleted in men with MA. Multifactorial regression analysis demonstrated a decrease in YBX2 expression in MA is due to decrease in COMP levels (p<0.0001). IF localized YBX2 protein in spermatocytes and round spermatids among fertile men, with rare YBX2 positive spermatocytes stained in LMA. PRM1&2 proteins were absent or abnormally sequestrated within spermatocytes.ConclusionsDecrease in YBX2 protein expression in men with LMA leads to loss of translational suppression and lack of PRM1 and PRM2 necessary to complete spermatogenesis.
Do below-ground genotypes influence above-ground microbiomes of grafted tomato plants?
Authors: Toju Hirokazu , Okayasu Koji , Notaguchi Michitaka 
Published: July 2018

AbstractBacteria and fungi form complex communities (microbiomes) in the phyllosphere and rhizosphere of plants, contributing to hosts’ growth and survival in various ways. Recent studies have suggested that host plant genotypes control, at least partly, microbial community compositions in the phyllosphere. However, we still have limited knowledge of how microbiome structures are determined in/on grafted crop plants, whose above-ground (scion) and below-ground (rootstock) genotypes are different with each other. By using eight varieties of grafted tomato plants, we examined how rootstock genotypes determine phyllosphere microbial assembly in field conditions. An Illumina sequencing analysis showed that both bacterial and fungal community structures did not significantly differ among tomato plants with different rootstock genotypes. Nonetheless, a further statistical analysis targeting respective microbial taxa suggested that some bacteria and fungi were preferentially associated with particular rootstock treatments. Specifically, a bacterium in the genus Deinococcus was found disproportionately from ungrafted tomato individuals. In addition, yeasts in the genus Hannaella were preferentially associated with the tomato individuals whose rootstock genotype was “Ganbarune”. Overall, this study suggests to what extent phyllosphere microbiome structures can be affected/unaffected by rootstock genotypes in grafted crop plants.
Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin
Authors: Wang Kwo-Kwang Abraham , Ng Tai L. , Wang Peng , Huang Zedu , Balskus Emily P. , van der Donk Wilfred A. 
Published: July 2018

AbstractFosfazinomycin and kinamycin are natural products that contain nitrogen-nitrogen (N-N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N-N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N-N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to NN bond-containing natural products wherein the N-N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N-N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.
Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques
Authors: Snyder-Mackler Noah , Sanz Joaquín , Kohn Jordan N. , Voyles Tawni N. , Pique-Regi Roger , Wilson Mark E. , Barreiro Luis B. , Tung Jenny 
Published: July 2018

ABSTRACTLow social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used anin vitroglucocorticoid challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression, but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression post-GC exposure. Regions that were more accessible in high status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the glucocorticoid receptor co-factor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation, and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.
Elevated plasma ceramide levels in post-menopausal women
Authors: Vozella Valentina , Basit Abdul , Piras Fabrizio , Realini Natalia , Armirotti Andrea , Bossù Paola , Assogna Francesca , Sensi Stefano L. , Spalletta Gianfranco , Piomelli Daniele 
Published: July 2018

AbstractCirculating ceramide levels are abnormally elevated in age-dependent pathologies such as cardiovascular diseases, obesity and Alzheimer’s disease. Nevertheless, the potential impact of age on plasma ceramide levels has not yet been systematically examined. In the present study, we quantified a focused panel of plasma ceramides and dihydroceramides in a cohort of 164 subjects (84 women) 19 to 80 years of age. After adjusting for potential confounders, multivariable linear regression analysis revealed a positive association between age and ceramide (d18:1/24:0) (β (SE) = 5.67 (2.38);p= .0198) and ceramide (d18:1/24:1) (β (SE) = 2.88 (.61);p< .001) in women, and between age and ceramide (d18:1/24:1) in men (β (SE) = 1.86 (.77);p= .0179). In women of all ages, but not men, plasma ceramide (d18:1/24:1) was negatively correlated with plasma estradiol (r = −0.294;p= .007). Finally,in vitroexperiments in human cancer cells expressing estrogen receptors showed that incubation with estradiol (10 nM, 24 h) significantly decreased ceramide accumulation. Together, the results suggest that aging is associated with an increase in circulating ceramide levels, which in post-menopausal women may be at least partially dependent on lower estradiol levels.
Familiarity modulates social approach toward stressed conspecifics in female rats
Authors: Rogers-Carter Morgan M. , Djerdjaj Anthony , Culp Amelia R. , Elbaz Joshua A. , Christianson John P. 
Published: July 2018

AbstractFamiliarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naïve and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.
RepB C-terminus mutation of an ori pRi vector affects plasmid copy number inAgrobacteriumand transgene copy number in plants
Authors: Vaghchhipawala Zarir , Radke Sharon , Nagy Ervin , Russell Mary L. , Johnson Susan , Gelvin Stanton B. , Gilbertson Larry , Ye Xudong 
Published: July 2018

AbstractA nativerepABCreplication origin, ori pRi, was previously reported as a single copy plasmid inAgrobacterium tumefaciensand can improve the production of transgenic plants with a single copy insertion of transgenes when it is used in binary vectors forAgrobacterium-mediatedtransformation. A high copy ori pRi variant plasmid, pTF::Ri, which does not improve the frequency of single copy transgenic plants, has been reported in the literature. Sequencing the high copy pTF::RirepABCoperon revealed the presence of two mutations: one silent mutation and one missense mutation that changes a tyrosine to a histidine (Y299H) in a highly conserved area of the C-terminus of the RepB protein (RepBY299H). Reproducing these mutations in the wild-type oriRi binary vector showed thatAgrobacteriumcells with the RepBY299Hmutation grow faster on both solidified and in liquid medium, and have higher plasmid copy number as determined by ddPCR. In order to investigate the impact of the RepBY299Hmutation on transformation and quality plant production, the RepBY299Hmutated ori pRi binary vector was compared with the original wild-type ori pRi binary vector and a multi-copy oriV binary vector in canola transformation. Molecular analyses of the canola transgenic plants demonstrated that the multi-copy ori pRi with the RepBY299Hmutation inAgrobacteriumcells lost the advantage of generating high frequency single copy, backbone-free transgenic plants compared to using the single copy wild-type ori pRi binary vector.
Functional grading of pericellular matrix surrounding chondrocytes: potential roles in signaling and fluid transport
Authors: Saadat F. , Lagieski M.J. , Birman V. , Thomopoulos S. , Genin G.M. 
Published: July 2018

AbstractThe extracellular matrix surrounding chondrocytes within cartilage and fibrocartilage has spatial gradients in mechanical properties. Although the function of these gradients is unknown, the potential exists for cells to tailor their mechanical microenvironment through these gradients. We hypothesized that these gradients enhance fluid transport around the cell during the slow loading cycles that occur over the course of a day, and that this enhancement changes the nature of the mechanical signals received at the surface of the cell. To test this hypothesis, we studied the effect of these gradients on the mechanical environment around a chondrocyte using a closed form, linearized model. Results demonstrated that functional grading of the character observed around chondrocytes in articular cartilage enhances fluid transport, and furthermore inverts compressive radial strains to provide tensile signals at the cell surface. The results point to several potentially important roles for functional grading of the pericellular matrix.
Fallen Pillars: The Past, Present, and Future Population Dynamics of a Rare, Specialist Coral-Algal Symbiosis
Authors: Chan Andrea N. , Lewis Cynthia L. , Neely Karen L. , Baums Iliana B. 
Published: July 2018

AbstractRare and ecologically specialized species are at greater risk of extinction. Rarity in terms of low genotypic diversity may be obscured in sessile foundation species that can reproduce asexually. Asexual propagules are often only distinguishable from sexual recruits through molecular tools. Thus, molecular markers are necessary to assess genotypic variation and population structure in clonal organisms such as corals. The global decline of corals has necessitated marker development for improved conservation of rare coral species. We infer past demographic changes, describe modern population structure, and quantify asexual reproduction of the uncommon Caribbean pillar coral, Dendrogyra cylindrus and its endosymbiotic dinoflagellate, Symbiodinium dendrogyrum using de novo microsatellite markers. Results show that D. cylindrus comprises three distinct populations in the Caribbean whereas the symbiont was differentiated into four populations. Thus, barriers to gene flow differ between host and symbiont. In Florida, host and symbiont reproduced mainly asexually, yielding lower genotypic diversity than predicted from census size. Models of past demographic events revealed no evidence of historical changes in population size, consistent with the geological record of D. cylindrus indicating it has been rare for hundreds of thousands of years. The most recent global thermal stress event triggered a severe disease outbreak among D. cylindrus in Florida, resulting in a precipitous population decline. Projections indicate a high likelihood that this species may become locally extinct within the coming decades. The ecosystem consequences of losing rare coral species and their symbionts with increasingly frequent extreme warming events are not known but require urgent study.
Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis
Authors: Flores E’Lissa M. , Woeller Collynn F. , Falsetta Megan L. , Susiarjo Martha , Phipps Richard P. 
Published: July 2018

AbstractThe obesity epidemic is developing into the most costly health problem facing the world. Obesity, characterized by excessive adipogenesis and enlarged adipocytes, promotes morbidities such as diabetes, cardiovascular disease and cancer. Regulation of adipogenesis is critical to our understanding of how fat cell formation causes obesity and associated health problems. Thy1 (also called CD90), a widely used stem cell marker, blocks adipogenesis and reduces lipid accumulation. Thy1 knockout-mice are prone to diet-induced obesity. While the importance of Thy1 in adipogenesis and obesity is now evident, how its expression is regulated is not. We hypothesized that DNA methylation plays a role in promoting adipogenesis and affects Thy1 expression. Using the methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-dC), we investigated whether DNA methylation alters Thy1 expression during adipogenesis in both mouse 3T3-L1 pre-adipocytes and mouse mesenchymal stem cells. Thy1 protein and mRNA levels were decreased dramatically during adipogenesis. However, 5-aza-dC treatment prevented this phenomenon. Pyrosequencing analysis shows that the CpG sites at the Thy1 locus are methylated during adipogenesis. These new findings highlight the potential role of Thy1 and DNA methylation in adipogenesis and obesity.
cis-regulatory architecture of a short-range EGFR organizing center in theDrosophila melanogasterleg
Authors: Newcomb Susan , Voutev Roumen , Jory Aurelie , Delker Rebecca K. , Slattery Matthew , Mann Richard S. 
Published: July 2018

AbstractWe characterized the establishment of an Epidermal Growth Factor Receptor (EGFR) organizing center (EOC) during leg development inDrosophila melanogaster. Initial EGFR activation occurs in the center of leg discs by expression of the EGFR ligand Vn and the EGFR ligand-processing protease Rho, each through single enhancers,vnEandrhoE, that integrate inputs from Wg, Dpp, Dll and Sp1. Deletion ofvnEandrhoEeliminatesvnandrhoexpression in the center of the leg imaginal discs, respectively. Animals with deletions of bothvnEandrhoE(but not individually) show distal but not medial leg truncations, suggesting that the distal source of EGFR ligands acts at short-range to only specify distal-most fates, and that multiple additional ‘ring’ enhancers are responsible for medial fates. Further, based on thecis-regulatory logic ofvnEandrhoEwe identified many additional leg enhancers, suggesting that this logic is broadly used by many genes duringDrosophilalimb development.Author SummaryThe EGFR signaling pathway plays a major role in innumerable developmental processes in all animals and its deregulation leads to different types of cancer, as well as many other developmental diseases in humans. Here we explored the integration of inputs from the Wnt- and TGF-beta signaling pathways and the leg-specifying transcription factors Distal-less and Sp1 at enhancer elements of EGFR ligands. These enhancers trigger a specific EGFR-dependent developmental output in the fly leg that is limited to specifying distal-most fates. Our findings suggest that activation of the EGFR pathway during fly leg development occurs through the activation of multiple EGFR ligand enhancers that are active at different positions along the proximo-distal axis. Similar enhancer elements are likely to control EGFR activation in humans as well. Such DNA elements might be ‘hot spots’ that cause formation of EGFR-dependent tumors if mutations in them occur. Thus, understanding the molecular characteristics of such DNA elements could facilitate the detection and treatment of cancer.
Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow
Authors: Bal A. , Pichon M. , Picard C. , Casalegno JS. , Valette M. , Schuffenecker I. , Billard L. , Vallet S. , Vilchez G. , Cheynet V. , Oriol G. , Assant S. , Gillet Y. , Lina B. , Brengel-Pesce K. , Morfin F. , Josset L. 
Published: July 2018

AbstractBackgroundIn recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking.MethodsA total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7).ResultsThe optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses).ConclusionsAlthough the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.
Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families
Authors: Wang Zhenyu , Huang Chen , Sun Yanxiu , Lv Huibin , Zhang Mingzhou , Li Xuemin 
Published: July 2018

AbstractPurposeAs the leading cause of the impairment of vision of children, congenital cataract is considered as a hereditary disease, especially autosomal dominant congenital cataract (ADCC). The purpose of this study is to identify the genetic defect of six Chinese families with ADCC.Subjects and MethodsSix Chinese families with ADCC were recruited in the study. (103 members in total, 96 members alive, 27 patients in total) Genomic DNA samples extracting from probands’ peripheral blood cells were captured the mutations using a specific eye disease enrichment panel with next generation sequencing. After initial pathogenicity prediction, sites with specific pathogenicity were screened for further validation. Sanger sequencing was conducted in the other individuals in the families and other 100 normal controls. Mutations definitely related with ADCC will then be analyzed by bioinformatics analysis. The pathogenic effect of the amino acid changes and structural and functional changes of the proteins were finally analyzed by bioinformatics analysis.ResultsSeven mutations in six candidate genes associated with ADCC of six families were detected (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A, WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). All the seven mutations were only detected on affected individuals in the families. Among them there are three novel mutations (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A) and four that have been reported (WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). RPGRIP1 (c.2669G>A) mutation and CRYBA4 (c.26C>T) mutation are predicted to be benign according to bioinformatics analysis while the other five mutations (EPHA2, PAX6, MYH9, CRYBA4 c.169T>C, WFS1) are thought to be pathogenic.ConclusionWe report two novel heterozygous mutations (MYH9 c.4150G>C and CRYBA4 c.169T>C) in six Chinese families supporting their vital roles in causing ADCC.