bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide analysis of microRNA signature in lung adenocarcinoma with EGFR exon 19 deletion
Authors: Ju Lixia , Han Mingquan , Li Xuefei , Zhao Chao 
Published: November 2015

AbstractPurposeThe findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and microRNAs can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer.Materials and methodsIn this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and its wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we have detected the microRNAs expression in serum of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type.ResultsThe expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type.ConclusionsIt is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 can be further explored for potential predictor and targeted biomarker when it is difficult to get the tumors.
High-density SNP array and genome sequencing reveal signatures of selection in a divergent selection rat model for aerobic running capacity
Authors: Ren Yu-yu , Koch Lauren G. , Britton Steven L. , Qi Nathan R. , Treutelaar Mary K. , Burant Charles F. , Li Jun Z. 
Published: November 2015

AbstractWe have previously established two lines of rat for studying the functional basis of aerobic exercise capacity (AEC) and its impact on metabolic health. The two lines, high capacity runners (HCR) and low capacity runners (LCR), have been selectively bred for high and low intrinsic AEC, respectively. They were started from the same genetically heterogeneous population and have now diverged in both AEC and many other physiological measures, including weight, body composition, blood pressure, body mass index, lung capacity, lipid and glucose metabolism, and natural life span. In order to exploit this rat model to understand the genomic regions under differential selection within the two lines, we used SNP genotype and whole genome pooled sequencing data to identify signatures of selection using three different statistics: runs of homozygosity, fixation index, and aberrant allele frequency spectrum, and developed a composite score that combined the three signals. we found that several pathways (ATP transport and fatty acid metabolism) are enriched in regions under differential selection. The candidate genes and pathways under selection will be integrated with the previous mRNA expression data and future F2 QTL results for a multi-omics approach to understanding the biological basis of AEC and metabolic traits.
Estimating Effect Sizes and Expected Replication Probabilities from GWAS Summary Statistics
Authors: Holland Dominic , Wang Yunpeng , Thompson Wesley K. , Schork Andrew , Chen Chi-Hua , Lo Min-Tzu , Witoelar Aree , Werge Thomas , O’Donovan Michael , Andreassen Ole A. , Dale Anders M. ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Enhancing Neuro Imaging Genetics through Meta Analysis Consortium
Published: November 2015

AbstractGenome-wide Association Studies (GWAS) result in millions of summary statistics (“z-scores”) for single nucleotide polymorphism (SNP) associations with phenotypes. These rich datasets afford deep insights into the nature and extent of genetic contributions to complex phenotypes such as psychiatric disorders, which are understood to have substantial genetic components that arise from very large numbers of SNPs. The complexity of the datasets, however, poses a significant challenge to maximizing their utility. This is reflected in a need for better understanding the landscape of z-scores, as such knowledge would enhance causal SNP and gene discovery, help elucidate mechanistic pathways, and inform future study design. Here we present a parsimonious methodology for modeling effect sizes and replication probabilities that does not require raw genotype data, relying only on summary statistics from GWAS substudies, and a scheme allowing for direct empirical validation. We show that modeling z-scores as a mixture of Gaussians is conceptually appropriate, in particular taking into account ubiquitous non-null effects that are likely in the datasets due to weak linkage disequilibrium with causal SNPs. The four-parameter model allows for estimating the degree of polygenicity of the phenotype – the proportion of SNPs (after uniform pruning, so that large LD blocks are not over-represented) likely to be in strong LD with causal/mechanistically associated SNPs – and predicting the proportion of chip heritability explainable by genome-wide significant SNPs in future studies with larger sample sizes. We apply the model to recent GWAS of schizophrenia (N=82,315) and additionally, for purposes of illustration, putamen volume (N=12,596), with approximately 9.3 million SNP z-scores in both cases. We show that, over a broad range of z-scores and sample sizes, the model accurately predicts expectation estimates of true effect sizes and replication probabilities in multistage GWAS designs. We estimate the degree to which effect sizes are over-estimated when based on linear-regression association coefficients. We estimate the polygenicity of schizophrenia to be 0.037 and the putamen to be 0.001, while the respective sample sizes required to approach fully explaining the chip heritability are 106and 105. The model can be extended to incorporate prior knowledge such as pleiotropy and SNP annotation. The current findings suggest that the model is applicable to a broad array of complex phenotypes and will enhance understanding of their genetic architectures.
Population size and the length of the chromosome blocks identical by descent over generations
Authors: Tiret Mathieu , Hospital Frédéric 
Published: November 2015

ABSTRACTIn all populations, as the time runs, crossovers break apart ancestor haplotypes, forming smaller blocks at each generation. Some blocks, and eventually all of them, become identical by descent because of the genetic drift. We have in this paper developed and benchmarked a theoretical prediction of the mean length of such blocks and used it to study a simple population model assuming panmixia, no selfing and drift as the only evolutionary pressure. Besides, we have on the one hand derived, for any user defined error threshold, the range of the parameters this prediction is reliable for, and on the other hand shown that the mean length remains constant over time in ideally large populations.
Timing of locomotor recovery modulated by thewhitegene inDrosophila
Authors: Xiao Chengfeng , Robertson R Meldrum 
Published: November 2015

AbstractLocomotor recovery from anoxia follows the restoration of disordered ion distributions and neuronal excitability. The time taken for locomotor recovery after 30 s anoxia (around 10 min) is longer than the time for the propagation of action potentials to be restored (less than 1 min) inDrosophilawild-type. We report here that thewhite(w) gene modulates the timing of locomotor recovery. Wild-type flies displayed fast and consistent recovery of locomotion from anoxia, whereas mutants ofwshowed significantly delayed recovery. Genetic analysis including serial backcrossing revealed a strong association between thewlocus and the timing of locomotor recovery, and haplo-insufficient function ofw+in promoting fast locomotor recovery. The locomotor recovery phenotype was independent of classic eye pigmentation, although both are associated with thewgene. Introducing up to four copies of mini-white(mw+) into w1118 was insufficient to promote fast and consistent locomotor recovery. However, flies carryingw+duplicated to Y chromosome showed wild-type-like fast locomotor recovery. Furthermore, RNAi knockdown ofwin neurons but not glia delayed locomotor recovery, and specifically, knockdown ofwin putative subsets of serotonin neurons was sufficient to delay the locomotor recovery. These data reveal an additional role forwin modulating the timing of locomotor recovery from anoxia.
The relaxin receptor Lgr3 mediates growth coordination and developmental delay duringDrosophila melanogasterimaginal disc regeneration
Authors: Jaszczak Jacob S. , Wolpe Jacob B. , Bhandari Rajan , Jaszczak Rebecca G. , Halme Adrian 
Published: November 2015

AbstractDamage toDrosophila melanogasterimaginal discs activates a regeneration checkpoint that 1) extends larval development and 2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/IGF/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of NOS in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that theDrosophilarelaxin receptor homologue Lgr3, a leucine-rich repeat-containing G-protein coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNAi disruption ofLgr3expression, we show that Lgr3 functions in the PG upstream of nitric oxide synthase (NOS), and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in the both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing.
ASAP: A Machine-Learning Framework for Local Protein Properties
Authors: Brandes Nadav , Ofer Dan , Linial Michal 
Published: November 2015

AbstractDetermining residue level protein properties, such as the sites for post-translational modifications (PTMs) are vital to understanding proteins at all levels of function. Experimental methods are costly and time-consuming, thus high confidence predictions become essential for functional knowledge at a genomic scale. Traditional computational methods based on strict rules (e.g. regular expressions) fail to annotate sites that lack substantial similarity. Thus, Machine Learning (ML) methods become fundamental in annotating proteins with unknown function. We present ASAP (Amino-acid Sequence Annotation Prediction), a universal ML framework for residue-level predictions. ASAP extracts efficiently and fast large set of window-based features from raw sequences. The platform also supports easy integration of external features such as secondary structure or PSSM profiles. The features are then combined to train underlying ML classifiers. We present a detailed case study for ASAP that was used to train CleavePred, a state-of-the-art protein precursor cleavage sites predictor. Protein cleavage is a fundamental PTM shared by a wide variety of protein groups with minimal sequence similarity. Current computational methods have high false positive rates, making them suboptimal for this task. CleavePred has a simple Python API, and is freely accessible via a web-based application. The high performance of ASAP toward the task of precursor cleavage is suited for analyzing new proteomes at a genomic scale. The tool is attractive to protein design, mass spectrometry search engines and the discovery of new peptide hormones. In summary, we illustrate ASAP as an entry point for predicting PTMs. The approach and flexibility of the platform can easily be extended for additional residue specific tasks. ASAP and CleavePred source code available athttps://github.com/ddofer/asap.
Elevated gene expression of most microglial markers, and reduced expression of most pyramidal neuron and interneuron markers, in postmortem autism cortex
Authors: Borges-Monroy Rebeca , Ponting Chris P. , Belgard T. Grant 
Published: November 2015

AbstractAutism Spectrum Disorders (ASD) are clinically and genetically heterogeneous. Nevertheless, a characteristic gene expression signature in postmortem cortex is shared across most ASD cases. Knowing whether this signature reflects changes in cells of particular types would help to determine the molecular, cellular, and anatomical etiology of ASD. To investigate we took advantage of cell type marker genes defined by recent single cell transcriptome sequencing from mouse or human cortex. We find that microglial markers showed significantly and substantially higher median expression in postmortem ASD than in control cortex for both mouse and human markers (21% higher for orthologous markers defined in mouse; 93% higher for human markers). In contrast, neuronal markers showed reduced median expression: 12% and 16% lower for mouse interneurons and pyramidal neurons, 40% lower for human neurons, and 36% lower for a class of human excitatory projection neurons. Cell type density alterations in ASD brains are indicated because distributions of these cell type markers are shifted concordantly. Importantly, orthologous mouse neuronal marker genes encoding proteins localized to diverse neuronal compartments all showed reduced median expression in ASD. Our results provide a framework for revealing the basis of transcriptomic differences in ASD. We propose comparing cell type density alterations in post-mortem tissue with and without these distinctive gene expression changes to reconcile results from stereological and transcriptomic studies.
Anin silicocomparison of reduced-representation and sequence-capture protocols for phylogenomics
Authors: Collins Rupert A. , Hrbek Tomas 
Published: November 2015

AbstractIn the age of genome-scale DNA sequencing, choice of molecular marker arguably remains an important decision in planning a phylogenetic study. Using published genomes from 23 primate species, we make a standardized comparison of four of the most frequently used protocols in phylogenomics,viz., targeted sequence-enrichment using ultraconserved element and exon-capture probes, and reduced genomic representation using restriction-site-associated DNA sequencing (RADseq and ddRAD-seq). Here we present a procedure to performin silicoextractions from genomes and create directly comparable datasets for each class of marker. We then compare these datasets in terms of both phylogenetic resolution and ability to consistently and precisely estimate clade ages using fossil-calibrated molecular-clock models. Furthermore, we were also able to directly compare these results to previously published datasets from Sanger-sequenced nuclear exons and mitochondrial genomes under the same analytical conditions. Our results show—although with the exception of the mitochondrial genome and ddRADseq datasets—that for uncontroversial nodes all data classes performed equally well, i.e. they recovered the same well supported topology. However, for one difficult-to-resolve node comprising a rapid diversification (subfamilial relationships among the Cebidae), we report well supported but conflicting topologies among the marker classes, likely the result of mismodelling of gene tree heterogeneity. Likewise, clade age estimates showed consistent discrepancies between datasets; for recent nodes, clade ages estimated by nuclear exon datasets were younger than those of the UCE, RAD and mitochondrial data, butvice versafor the deepest nodes in the primate phylogeny. This effect can be explained by temporal differences in phylogenetic informativeness and choice of clock model used. Finally, we conclude by emphasizing that while huge numbers of loci are probably not required for uncontroversial phylogenetic questions—for which practical considerations such as cost and ease of data generation/sharing/aggregating therefore become increasingly important—accurately modelling heterogeneous data remains as relevant as ever for the more recalcitrant problems.
CASH algorithm versus 3‐point checklist and its modified version in evaluation of melanocytic pigmented skin lesions: The 4‐point checklist
Authors: di Meo Nicola , Stinco Giuseppe , Bonin Serena , Gatti Alessandro , Trevisini Sara , Damiani Giovanni , Vichi Silvia , Trevisan Giusto 
Published: November 2015

AbstractDermoscopy, in expert hands, increases accuracy, sensitivity and specificity in diagnosis of pigmented skin lesions of a single operator, compared with clinical examination. Simplified algorithmic methods have been developed to help less expert dermoscopists in diagnosis of melanocytic lesions. This study included 125 melanocytic skin lesions divided into melanocytic nevi, dysplastic nevi and thin melanomas (<1 mm). We compared the 3‐point checklist and CASH algorithm to analyze different pigmented skin lesions. Based on preliminary results, we proposed a new modified algorithm, called the 4‐point checklist, whose accuracy is similar to the CASH algorithm and whose simplicity is similar to the 3‐point checklist.
Molecular cloning and functional characterization of a novel i‐type lysozyme in the freshwater mussel Cristaria plicata
Authors: Dai Wenjuan , Wu Dan , Zhang Ming , Wen Chungen , Xie Yanhai , Hu Baoqing , Jian Shaoqing , Zeng Mingyu , Tao Zhiying 
Published: November 2015

ABSTRACTThe freshwater bivalve Cristaria plicata, which is widely distributed in Eastern Asia, is a key species in the pearl culture industry. In this study, a novel invertebrate‐type lysozyme, designated as CpLYZ2, was cloned from hemocytes of C. plicata. This lysozyme shares high sequence identity and is homologous to a previously identified lysozyme CpLYZ1 isolated from C. plicata and with HcLyso3 isolated from Hyriopsis cumingii. The full‐length cDNA of CpLYZ2 is 913 bp long, which includes an open reading frame (ORF) of 486 bp, a 3′ untranslated region (UTR) of 389 bp and a 5′ UTR of 38 bp. The ORF encodes a putative polypeptide of 161 amino acids with a predicted molecular mass of 18.2 kDa and a theoretical isoelectric point of 6.56. CpLYZ2 mRNA transcripts can be detected in hemocytes, hepatopancreas, muscle, gills and mantle tissues, the greatest expression being observed in the gills. CpLYZ2 expression in hemocytes, hepatopancreas and gills increased significantly after the mussel was challenged with Aeromonas hydrophila. Furthermore, the optimal pH and temperature for enzyme activity of the recombinant CpLYZ2 were 5.5 and 50°C, respectively. The recombinant lysozyme protein exhibited bacteriolytic activity against Escherichia coli, A. hydrophila, Staphyloccocus aureus, Bacillus subtilis, Streptococcus sp. and Staphylococcus epidermidis. The findings of this study help to elucidate immune responses in molluscs and will thus expedite disease management of these key freshwater species, in turn boosting pearl culture in eastern Asia.
Consumption of probiotic Lactobacillus rhamnosus (MTCC: 5897) containing fermented milk plays a key role in development of the immune system in newborn mice during the suckling–weaning transition
Authors: Saliganti Vamshi , Kapila Rajeev , Kapila Suman 
Published: November 2015

ABSTRACTEarly infancy, the period when offspring rely not only on their own immunity to combat food‐borne antigens but also acquire immunity through maternal sources (via transplacental routes and breast milk), is critical for immune system development Hence the present study was designed to evaluate the effect on offspring of administration of probiotic‐containing fermented milk (PFM) either to mothers during the suckling period or to their offspring after weaning either separately or sequentially. PFM‐fed mice showed enhanced leukocyte functionality in offspring as evidenced by significantly (P < 0.05) increased release of lysosomal enzymes (β‐galactosidase, β‐glucuronidase) in peritoneal fluid and nitric oxide production in culture supernatants of activated macrophages. Further, remarkably reduced levels (P < 0.01) of inflammatory markers (TNF‐α, monocyte chemotactic protein‐1) and allergic antibodies (total and milk specific IgE) were observed in offspring where PFM was fed either to them or to their mothers. However, considerably increased levels (P < 0.05) of SIgA were found in the guts of control and experimental groups animals irrespective of their exposure to PFM. Restoration of Th1/Th2 homeostasis further confirmed the useful effects of PFM supplementation by shifting the cytokine profile (IL‐4, IFN‐γ and IL‐10) with increased IFN‐γ/IL‐4 and reduced IgE/Ig2Ga ratios. Hence, it is logical to conclude that administration of Lactobacillus rhamnosus‐containing (MTCC:5897) fermented milk to mothers during the suckling period and to their offspring after weaning has beneficial effects on the development of newborns immune systems; this effect appears to be more pronounced when mothers are fed with it.
Effect of interleukin‐2 receptor antagonists on new‐onset diabetes after liver transplantation: A retrospective cohort study
Authors: Xue Mengjuan , Lv Chaoyang , Chen Xianying , Huang Xiaowu , Sun Qiman , Wang Ting , Liang Jing , Zhang Yao , He Shunmei , Gao Jian , Zhou Jian , Yu Mingxiang , Fan Jia , Gao Xin 
Published: November 2015

AbstractBackgroundThe aim of the present retrospective observational study was to examine the effect of interleukin‐2 receptor antagonists (IL‐2Ra) on new‐onset diabetes after transplantation (NODAT) in liver transplant recipients.MethodsPre‐ and postoperative clinical data of 781 patients undergoing liver transplantation between April 2001 and December 2014 at Zhongshan Hospital, Fudan University, were analyzed. Patients were divided into two groups depending on the use of IL‐2Ra (IL‐2Ra and non‐IL‐2Ra). The cumulative incidence of NODAT was compared between the IL‐2Ra and non‐IL‐2Ra groups and the effect of IL‐2Ra on the incidence of NODAT in liver transplant recipients was evaluated.ResultsOf the 781 patients in the study, 451 received IL‐2Ra. During follow‐up, 138 (41.8%) and 137 (30.4%) patients in the non‐IL‐2Ra and IL‐2Ra groups, respectively, developed NODAT (P = 0.001). The cumulative incidence of NODAT at 1, 3, 5, and 8 years after transplantation in the IL‐2Ra group was 30%, 38%, 45%, and 54%, respectively; these values were substantially lower than corresponding values for the non‐IL‐2Ra group (P < 0.05). Cox regression analyses showed that IL‐2Ra was a protective factor against NODAT development (odds ratio 0.685; 95% confidence interval 0.473–0.991; P = 0.044). This was independent of age, sex, donor type, hepatitis virus infection, body mass index, history of hypertension, preoperative liver function, preoperative fasting plasma glucose, total cholesterol, and total triglyceride levels, severity of liver cirrhosis, acute rejection, initial immunosuppressant regimen type, and postoperative immunosuppressant levels.ConclusionIn conclusion, IL‐2Ra reduces the risk of NODAT in liver transplant recipients.