bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micro-indentation and optical coherence tomography for the mechanical characterization of embryos: Experimental setup and measurements on fixed chicken embryos
Authors: Marrese Marica , Antonovaité Nelda , Nelemans Ben K.A. , Smit Theodoor H. , Iannuzzi Davide 
Published: February 2019

Summary statementWe introduce an experimental technique that combines micro-indentation and optical coherence tomography to map the viscoelastic properties of embryonic tissue and investigate correlations between local mechanical features and tissue morphology.AbstractThe investigation of the mechanical properties of embryos is expected to provide valuable information on the phenomenology of morphogenesis. It is thus believed that, by mapping the viscoelastic features of an embryo at different stages of growth, it may be possible to shed light on the role of mechanics in embryonic development. To contribute to this field, we present a new instrument that can determine spatiotemporal distributions of mechanical properties of embryos over a wide area and with unprecedented accuracy. The method relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with Optical Coherence Tomography, which can reveal changes in tissue morphology and help the user to localize the indentation locations. To prove the working principle, we have collected viscoelasticity maps of fixed HH11-HH12 chicken embryos. Our study highlights the nonlinear behavior of the tissue and qualitatively shows the correlation between local mechanical properties and tissue morphology for different regions of interest.
QTL and genetic analysis controlling fiber quality traits using paternal backcross population in Upland Cotton
Authors: Ma Lingling , Su Ying , Wang Yumei , Nie Hushai , Cui Yupeng , Cheng Cheng , Wang Meiyan , Hua Jinping 
Published: February 2019

ABSTRACTIn present study, F14recombinant inbred line (RIL) population was backcrossed to paternal parent for a paternal backcross (BC/P) population, deriving from one Upland cotton hybrid. Three repetitive BC/P field trials and one BC/M field trial were performed including both two BC populations and the original RIL population. Totally, for fiber quality traits, 24 novel QTLs were detected and 13 QTLs validated previous results. And 19 quantitative trait loci (QTL) in BC/P populations explained 5.01% - 22.09% of phenotype variation (PV). Among the 19 QTLs, three QTLs were detected simultaneously in BC/M population. The present study provided novel alleles of male parent for fiber quality traits with positive genetic effects. Particularly,qFS-Chr3-1controlling fiber strength explained 22.09% of PV in BC/P population, which increased 0.48 cN/tex for fiber strength. A total of seven, two, eight, two and six QTLs explained over 10.00% of PV for fiber length, fiber uniformity, fiber strength, fiber elongation and fiber micronaire, respectively. In the RIL population, six common QTLs detected in more than one environment such asqFL-Chr1-2,qFS-Chr5-1,qFS-Chr9-1,qFS-Chr21-1,qFM-Chr9-1andqFM-Chr9-2. Two common QTLs ofqFE-Chr2-2(TMB2386-SWU12343) andqFM-Chr9-1(NAU2873-CGR6771) explained 22.42% and 21.91% of PV. In addition, a total of 142 and 46 epistatic QTLs and QTL × environments (E-QTLs and QQEs) were identified in RIL-P and BC/P populations, respectively.
Regulation of bacterial surface attachment by a network of sensory transduction proteins
Authors: Reyes Ruiz Leila M. , Fiebig Aretha , Crosson Sean 
Published: February 2019

AbstractBacteria are often attached to surfaces in natural ecosystems. A surface-associated lifestyle can have advantages, but shifts in the physiochemical state of the environment may result in conditions in which attachment has a negative fitness impact. Therefore, bacterial cells employ numerous mechanisms to control the transition from an unattached to a sessile state. TheCaulobacter crescentusprotein HfiA is a potent developmental inhibitor of the secreted polysaccharide adhesin known as the holdfast, which enables permanent attachment to surfaces. Multiple environmental cues influence expression ofhfiA, but mechanisms ofhfiAregulation remain largely undefined. Through a forward genetic selection, we have discovered a multi-gene network encoding a suite of two-component system (TCS) proteins and transcription factors that coordinately controlhfiAtranscription and surface adhesion. The hybrid HWE-family histidine kinase, SkaH, is central among these regulators and forms heteromeric complexes with the kinases, LovK and SpdS. The response regulator SpdR indirectly inhibitshfiAexpression by activating two XRE-family transcription factors that directly bind thehfiApromoter to repress its transcription. This study provides evidence for a model in which a consortium of environmental sensors and transcriptional regulators integrate environmental cues at thehfiApromoter to control the attachment decision.Author summaryLiving on a surface within a community of cells confers a number of advantages to a bacterium. However, the transition from a free-living state to a surface-attached lifestyle should be tightly regulated to ensure that cells avoid adhering to toxic or resource-limited niches. Many bacteria build adhesive structures at their surfaces that enable attachment. We sought to discover genes that control development of theCaulobacter crescentussurface adhesin known as the holdfast. Our studies uncovered a network of signal transduction proteins that coordinately control the biosynthesis of the holdfast by regulating transcription of the holdfast inhibitor,hfiA. We conclude thatC. crescentususes a multi-component regulatory system to sense and integrate environmental information to determine whether to attach to a surface, or to remain in an unattached state.
Gene-Set Enrichment with Mathematical Biology
Authors: Cochran Amy L , Nieser Kenneth , Forger Daniel B , Zöllner Sebastian , McInnis Melvin G 
Published: February 2019

AbstractGene-set analyses measure the association between a disease of interest and a set of genes related to a biological pathway. These analyses often incorporate gene network properties to account for the differential contributions of each gene. Extending this concept further, mathematical models of biology can be leveraged to define gene interactions based on biophysical principles by predicting the effects of genetic perturbations on a particular downstream function. We present a method that combines gene weights from model predictions and gene ranks from genome-wide association studies into a weighted gene-set test. Using publicly-available summary data from the Psychiatric Genetics Consortium (n=41,653; ~9) million SNPs), we examine an a priori hypothesis that intracellular calcium ion concentrations contribute to bipolar disorder. In this case study, we are able to strengthen inferences from a P-value of 0.081 to 1.7×10−4 by moving from a general calcium signaling pathway to a specific model-predicted function.
Chromosomal rearrangements at hypomethylated Satellite 2 sequences are associated with impaired replication efficiency and increased fork stalling
Authors: Delpu Yannick , McNamara Thomas , Griffin Patrick , Kaleem Suhail , Narayan Shubhada , Schildkraut Carl , Miga Karen , Tahiliani Mamta 
Published: February 2019

AbstractCancer cells, aging cells, and cells from patients with the developmental disorder Immunodeficiency, Centromeric instability, and Facial anomalies (ICF) syndrome frequently display a striking loss of DNA methylation (hypomethylation) that is accompanied by increased DNA damage and chromosomal rearrangements. Despite the robust link, the mechanism by which hypomethylation leads to genomic instability is poorly understood. We report that the human pericentromeric repeat sequence Satellite 2 (SAT2) poses challenges to the DNA replication machinery when hypomethylated. Loss of methylation at SAT2 is associated with increased frequencies of chromosomal abnormalities and DNA damage. Hypomethylation of SAT2 is associated with elevated levels of replication stress signaling, and chromosomal abnormalities involving SAT2 are enhanced by low levels of aphidicolin-induced replication stress. To investigate the basis for these chromosomal abnormalities, we developed a single-molecule approach employing DNA combing to examine the progress of replication forks through SAT2 at the resolution of a single DNA molecule. Our analysis of replicating SAT2 molecules provides in vivo evidence that hypomethylation of SAT2 strongly decreases the efficiency of replicating these sequences suggesting that hypomethylation results in the formation of barriers to the replication machinery. Consistent with increased frequency of fork stalling at these sequences, we find increased levels of single-stranded DNA (ssDNA) binding protein RPA2 as well as asymmetric progression of sister replication forks within hypomethylated SAT2 sequences. Together these findings indicate that impaired replication triggers the formation of chromosomal aberrations observed at hypomethylated SAT2 sequences and also suggests a mechanistic basis for how the loss of DNA methylation may contribute to genomic instability in diverse pathological conditions.
dbMTS: a comprehensive database of putative human microRNA target site SNVs and their functional predictions
Authors: Li Chang , Swartz Michael D. , Yu Bing , Bai Yongsheng , Liu Xiaoming 
Published: February 2019

AbstractmicroRNAs (miRNAs) are short non-coding RNAs that can repress the expression of protein coding messenger RNAs (mRNAs) by binding to the 3’UTR of the target. Genetic mutations such as single nucleotide variants (SNVs) in the 3’UTR of the mRNAs can disrupt this regulatory effect. In this study, we presented dbMTS, the database for miRNA target site (MTS) SNVs, which includes all potential MTS SNVs in the 3’UTR of human genome along with hundreds of functional annotations. This database can help studies easily identify putative SNVs that affect miRNA targeting and facilitate the prioritization of their functional importance. dbMTS is freely available at: https://sites.google.com/site/jpopgen/dbNSFP.
Cholangiocarcinoma presents a distinct myeloid-derived suppressor cell signature compared to other hepatobiliary cancers
Authors: Bayik Defne , Lauko Adam J. , Roversi Gustavo A. , Serbinowski Emily , Acevedo-Moreno Lou-Anne , Lanigan Christopher , Orujov Mushfig , Lo Alice , Alban Tyler J. , Silver Daniel J. , Brown J. Mark , Allende Daniela S. , Aucejo Federico N. , Lathia Justin D. 
Published: February 2019

AbstractMyeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSC in other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome. Mechanistic studies indicated that the oncometabolite D-2-hydroxyglutarate resulting from isocitrate dehydrogenase 1 mutation could be a limiting factor of MDSC accumulation in CCA patients. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.
Evaluating brain cell marker genes based on differential gene expression and co-expression
Authors: Dai Rujia , Chen Yu , Jiao Chuan , Dai Jiacheng , Chen Chao , Liu Chunyu 
Published: February 2019

AbstractReliable identification of brain cell types is necessary for studying brain cell biology. Many brain cell marker genes have been proposed, but their reliability has not been fully validated. We evaluated 540 commonly-used marker genes of astrocyte, microglia, neuron, and oligodendrocyte with six transcriptome and proteome datasets from purified human and mouse brain cells (n=125). By setting new criteria of cell-specific fold change, we identified 22 gold standard marker genes (GSM) with stable cell-specific expression. Our results call into question the specificity of many proposed marker genes. We used two single-cell transcriptome datasets from human and mouse brains to explore the co-expression of marker genes (n=3337). The mouse co-expression modules were perfectly preserved in human transcriptome, but the reverse was not. Also, we proposed new criteria for identifying marker genes based on both differential expression and co-expression data. We identified 16 novel candidate marker genes (NCM) for mouse and 18 for human independently, which have the potential for use in cell sorting or other tagging techniques. We validated the specificity of GSM and NCM by in-silico deconvolution analysis. Our systematic evaluation provides a list of credible marker genes to facilitate correct cell identification, cell labeling, and cell function studies.
On the front line of Klebsiella pneumoniae surface structures understanding: establishment of Fourier Transform Infrared (FT-IR) spectroscopy as a capsule typing method
Authors: Rodrigues Carla , Sousa Clara , Lopes João Almeida , Novais Ângela , Peixe Luísa 
Published: February 2019

ABSTRACTGenomics-based population analysis of multidrug resistant (MDR) Klebsiella pneumoniae (Kp) motivated a renewed interest on capsule (K) types given their importance as evolutionary and virulence markers of clinically relevant strains. However, there is a gap between genotypic based predictions and information on capsular polysaccharide structure and composition. We used molecular genotypic, comparative genomics, biochemical and phenotypic data on the cps locus to support the usefulness of Fourier-Transform Infrared (FT-IR) spectroscopy as a phenotypic approach for K-type characterization and identification. The approach was validated with a collection of representative MDR Kp isolates from main lineages/Clonal Groups (CGs) involved in local or nationwide epidemics in 6 European and South American countries. FT-IR-based K-type assignments were compared with those obtained by genotypic methods and WGS (cps operon), and further complemented with data on the polysaccharide composition and structure of known K-types.We demonstrate that our FT-IR-based spectroscopy approach can discriminate all 21 K-types identified with a resolution comparable (or even higher) to that provided by WGS, considered gold-standard methodology. Besides contributing to enlighten K-type diversity among a significant MDR Kp collection, the specific associations between certain K-types and Kp lineages identified in different geographic regions over time support the usefulness of our FT-IR-based approach for strain typing. Additionally, we demonstrate that FT-IR discriminatory ability is correlated with variation on the structure/composition of known K-types and, supported on WGS data, we were able to predict the sugar composition and chemical structure of new KL-types. Our data revealed an unprecedent resolution at a quick and low-cost rate of Kp K-types at the phenotypic level. Our FT-IR spectroscopy-based approach might be extremely useful not only as a cost-effective Kp typing tool, but also to improve our understanding on sugar-based coating structures of high relevance for strain evolution and host adaptation.
Magnitude and Correlates of Caesarean Section in Urban and Rural Areas: A Multivariate Study in Vietnam
Authors: Loenzien Myriam de , Schantz Clémence , Luu Bich Ngoc , Dumont Alexandre 
Published: February 2019

AbstractCaesarean section can prevent maternal and neonatal mortality and morbidity. However, it involves risks and high costs which can be a burden, especially in low and middle income countries. The international healthcare community considers the optimal caesarean rate to be between 10% and 15%. The aim of this study is to assess its magnitude and correlates among women of reproductive age in urban and rural areas in Vietnam. We analyzed microdata from the national Multiple Indicator Cluster Survey (MICS) conducted in 2013-2014 using representative sample of households at the national level as well as regarding the urban and the rural areas. A total of 1,378 women who delivered in institutional settings in the two years preceding the survey were included. Frequency and percentage distributions of the variables were performed. Bivariate and multivariate logistic regression analysis were undertaken to identify the factors associated with caesarean section. Odds ratios with 95% confidence interval were used to ascertain the direction and strength of the associations. The overall CS rate among the women who delivered in healthcare facilities in Vietnam is particularly high (29.2%) with regards to WHO standards. After controlling for significant characteristics, living in urban areas more than doubles the likelihood of undergoing a CS (OR = 2.31; 95% CI 1.79 to 2.98). Maternal age at delivery over 35 is a major positive correlate of CS. Beyond this common phenomenon, distinct lines of socioeconomic and demographic cleavage operate in urban versus rural areas. The differences regarding correlates of CS according to the place of residence suggest that specific measures should be taken in each setting to allow women to access childbirth services appropriate to their needs. Further research is needed on this topic.
Disease spectrum and outcomes among elderly patients in two tertiary hospitals in Dar es Salaam, Tanzania
Authors: Tumaini Basil , Munseri Patricia , Pallangyo Kisali 
Published: February 2019

AbstractBackgroundThere has been an increase in the number of individuals aged ≥60 years in Tanzania and in sub Saharan Africa in general due to improved survival. However there is scarcity of data on the disease burden, patterns and outcomes following admission in this population. We therefore describe the pattern of diagnoses, outcomes and factors associated with the outcomes among elderly patients admitted at Muhimbili National Hospital (MNH) and Jakaya Kikwete Cardiac Institute (JKCI) medical wards.MethodologyWe prospectively enrolled patients aged ≥60 years (elderly) admitted through MNH Emergency Medicine to the MNH medical wards and JKCI. ICD 10 was used to code for disease diagnosis at discharge or death. Modified Barthel index was used to assess for functional activity on admission and at discharge.ResultsWe enrolled 336 elderly participants, who comprised 30.1% of all medical admissions. The mean age was 70.6 years; 50% were female and 263 (78.3%) had comorbidities with an average of 2 diagnoses per participant. The most common diagnoses were: hypertension (44.9%), stroke (31.5%), heart failure (18.5%), pneumonia (17.9%), diabetes mellitus (17.3%) and chronic kidney disease (16.4%). The median duration of hospital stay was 5 days and in-hospital mortality was 25.6%. Non-communicable diseases (NCDs) accounted for 65% of the deaths and 50% of the deaths occurred within 72 hours of hospitalization. A modified Barthel score of ≤20 on admission was associated with 15 times increased risk of death (p<0.001).ConclusionNCDs were the most common diagnoses and cause of death among patients aged ≥60 years admitted to the medical wards. In-hospital mortality was high and occurred within 72 hours of hospitalization. A modified Barthel score <20 on admission was associated with mortality.
Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing direction-selective retinal ganglion cells
Authors: Winkelman Beerend H.J. , Howlett Marcus H. , Hölzel Maj-Britt , Joling Coen , Fransen Kathryn H. , Pangeni Gobinda , Kamermans Sander , Sakuta Hiraki , Noda Masaharu , Simonsz Huibert J. , McCall Maureen A. , De Zeeuw Chris I. , Kamermans Maarten 
Published: February 2019

AbstractCongenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here we investigated whether nystagmus associated with congenital stationary nightblindness (CSNB) can result from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lack functional nyctalopin protein (NYX, nyx) in ON bipolar cells (ON-BC) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7Hz. nob ON direction selective ganglion cells (ON-DSGC), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GC) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light. Retinal pharmacological manipulations that blocked nob ON-DSGC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced oscillation frequency of nob ON-DSGCs also reduced oscillation frequency of their eye movements. We conclude that, in nob mice, oscillations of retinal ON-DSGCs cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus paving the way for development of therapeutic strategies.
Elevated CO2 induces age-dependent restoration of growth and metabolism in gibberellin-deficient plants
Authors: Gasparini Karla , Costa Lucas C. , Brito Fred A. L. , Pimenta Thaline M. , Cardoso Flávio Barcellos , Araújo Wagner L. , Zsögön Agustín , Ribeiro Dimas M. 
Published: February 2019

AbstractMain conclusion The effect of elevated [CO2] on the growth of tomato plants with reduced GA content is influenced by developmental stage.The increase of carbon dioxide (CO2) in the atmosphere during the last decades has aroused interest in the function of this gas in the growth and development of plants. Despite the known association between elevated CO2 concentration ([CO2]) and plant growth, its effects in association with gibberellin (GA), plant hormone that regulates de major aspects of plant growth, are still poorly understood. Therefore, we evaluated the effect of elevated [CO2] on growth and primary metabolism in tomato plants with drastic reduction in GA content (gib-1) at two different growth stages (21 and 35 days after germination, dag). Disruption on growth, photosynthetic parameters and primary metabolism were restored when gib-1 plants were transferred to elevated [CO2] at 21 dag. Elevated [CO2] also stimulated growth and photosynthetic parameters in Wild type (WT) plants at 21 dag, however, minor changes were observed in the level of primary metabolites. At 35 dag, elevated [CO2] did not stimulate growth in WT plants and gib-1 mutants showed their characteristic stunted growth phenotype.