Biology subjects

Yang, X.

Publications and source records attributed to Yang, X..

966 records · Page 54Linked to original sources

bioRxiv2017

Competitive ability of a tetraploid selfing species (Capsella bursa-pastoris) across its expansion range and comparison with its sister species

Self-fertilization is often associated with ecological traits corresponding to the ruderal strategy in Grimes Competitive-Stress-tolerant-Ruderal (CSR) classification of ecological strategies. Consequently, selfers are expected to be less competitive than outcrossers, either because of a colonization/competition trade-off or because of the deleterious genetic effects of selfing. Range expansion could reduce further competitive ability while polyploidy could mitigate the effects of selfing. Although suggested by meta-analyses, these predictions have not been directly tested yet. We compared the competitive ability of four Capsella species differing by their mating system and ploidy level. We found that the two diploid selfing species (C. rubella and C. orientalis) were more sensitive to competition than the diploid outcrosser (C. grandiflora), and that the tetraploid selfer (C. bursa-pastoris) was intermediate. Within C. bursa-pastoris, we also found that sensitivity to competition increased in parallel to range expansion. These results highlight the possible roles of ecological context and ploidy in the evolutionary trajectories of selfing species.

evolutionary biology↗

bioRxiv2017

Strong positive biodiversity-productivity relationships in a subtropical forest experiment

Forest ecosystems contribute substantially to global terrestrial primary productivity and climate regulation, but, in contrast to grasslands, experimental evidence for a positive biodiversity-productivity relationship in highly diverse forests is still lacking1. Here, we provide such evidence from a large forest biodiversity experiment with a novel design2 in subtropical China. Productivity (stand-level tree basal area, aboveground volume and carbon and their annual increment) increased linearly with the logarithm of tree species richness. Additive partitioning3 showed that increasing positive complementarity effects combined with weakening negative selection effects caused a strengthening of the relationship over time. In 2-species mixed stands, complementary effects increased with functional distance and selection effects with vertical crown dissimilarity between species. Understorey shrubs reduced stand-level tree productivity, but this effect of competition was attenuated by shrub species richness, indicating that a diverse understorey may facilitate overall ecosystem functioning. Identical biodiversity-productivity relationships were found in plots of different size, suggesting that extrapolation to larger scales is possible. Our results highlight the potential of multi-species afforestation strategies to simultaneously contribute to mitigation of climate change and biodiversity restoration.

ecology↗

bioRxiv2017

HPCDb: an integrated database of pancreatic cancer

We have established a database of Human Pancreatic Cancer (HPCDb) through effectively mining, extracting, analyzing, and integrating PC-related genes, single-nucleotide polymorphisms (SNPs), and microRNAs (miRNAs), now available online at http://www.pancancer.org/. Data were extracted from established databases, [≥]5 published literature (PubMed), and microarray chips (screening of differentially expressed genes using limma package in R, |log2 fold change (FC)| > 1). Further, protein-protein interactions (PPIs) were investigated through the Human Protein Reference Database. miRNA-target relationships were also identified using the online software TargetScan. Currently, HPCDb contains 3284 genes, 120 miRNAs, 589 SNPs, 10,139 PPIs, and 3904 miRNA-target pairs. The detailed information on PC-related genes (e.g., gene identifier (ID), symbol, synonyms, full name, chip sets, expression alteration, PubMed ID, and PPIs), miRNAs (e.g., accession number, chromosome location, related disease, PubMed ID, and miRNA-target interactions), and SNPs (e.g., SNP ID, allele, gene, PubMed ID, chromosome location, and disease) is presented through user-friendly query interfaces or convenient links to NCBI GEO, NCBI PubMed, NCBI Gene, NCBI dbSNP, and miRBase. Overall, HPCDb provides biologists with relevant information on human PC-related molecules at multiple levels, helping to generate new hypotheses or identify candidate markers.

bioinformatics↗

bioRxiv2017

GADD45α regulates cell proliferation and DNA repair of BRL-3A cells that treated by FZD/UVC via P38, JNK, CDC2/CCNB1, AKT and MTOR pathways

GADD45 is a stress-induced gene activated by a variety of stress stimuli, including ultraviolet and ionizing radiation, and involved in cell cycle regulation, apoptosis, maintenance, genomic stability, DNA repair and immune response. However, the effects and regulatory mechanism of GADD45 on proliferation, apoptosis and DNA damage repair of hepatocytes in liver regeneration remains unclear. In this study overexpression of GADD45 significantly inhibited the cell viability, proliferation, the number of cells in G1 and S phases, and of furazolidone (FZD) or UVC induced apoptosis of BRL-3A cells and decreased the inhibition of FZD/UVC on the viability, proliferation of BRL-3A cells, while increased the number of cells in G2/M phase of BRL-3A cells and FZD/UVC induced S phase arrest. Downregulated GADD45 induced the viability, proliferation, the number of cells in S and G2/M phases and the inhibition of FZD/UVC on the viability, proliferation of BRL-3A cells increased, while decreased apoptosis, the number of cells in G1 phases of BRL-3A cells and FZD/UVC induced S phase arrest. The results of qRT-PCR and western blot showed that genes/proteins related to P38MAPK, JNK, CDC2/CCNB1, AKT and MTOR signaling pathways were significantly changed in normal BRL-3A cells. The expression profiles of cell cycle, proliferation and apoptosis related genes/proteins in FZD/UVC treated BRL-3A cells were also detected by qRT-PCR and western blot, and the results indicated that the expression of Myc, Bcl-2, Ccnd1, PCNA, P21, Ccnb1, Caspase3, Caspase8, Caspase9 and Bax have significantly changes.

cell biology↗

bioRxiv2017

Beyond Autoantibodies: Biological Roles Of Human Autoreactive B Cells In Rheumatoid Arthritis Revealed By Whole Transcriptome Profiling

Although the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. Here we present the first comprehensive transcriptome profile of human autoreactive B cells in an autoimmune disease by performing RNA-sequencing of citrulline-specific B cells from RA patients. In order to facilitate a comprehensive understanding of the profile of these citrulline-specific (RA-CCPPOS) B cells, we performed comparative analyses to both citrulline-negative (RA-CCPNEG) B cells from the same donors, and identified 431 differentially expressed genes (DEGs); and hemagglutinin-specific (HA) B cells from healthy individuals and identified 1658 DEGs. Three-way comparisons of these B cell populations demonstrated that RA-CCPPOS B cells, in comparison to the RA-CCPNEG B cells, demonstrate a potential role in protein citrullination and inflammation; RA-CCPPOS B cells in comparison to HA-specific B cells demonstrate RA-specific signatures like the expression of pro-inflammatory cytokines, chemokines, costimulatory molecules and B-cell activation cascades; and all B cells from RA patients demonstrated a significant impact of the multitude of TNF signaling pathways. Furthermore, transcription factor profiling suggested that cyclic AMP (cAMP) related pathways and downstream signaling molecules are selectively enriched in RA-CCPPOS cells in comparison to the other two B cell subsets. We advanced the understanding of the citrulline reactive B cells in RA pathophysiology by documenting and validating two novel observations in independent cohorts of patients: (1) the expression of IL15R is restricted to citrulline-specific cells within RA patients and the concentration of soluble IL15R is elevated in the sera of RA patients, (2) B cells from RA patients are capable of producing epidermal growth factor ligand, amphiregulin (AREG) which in turn has a direct impact on the mechanistic effectors of RA, osteoclasts and fibroblastlike synoviocytes (FLS). Overall, our comprehensive dataset identifies several existing FDA-approved drugs that can potentially be repurposed for RA and can serve as a foundation for studying the multi-faceted roles of B cells in other autoimmune diseases.

immunology↗

bioRxiv2017

Identity-By-Descent Refines Mapping Of Candidate Regions For Preaxial Polydactyly In A Large Chinese Pedigree

Preaxial polydactyly (PPD) is congenital hand malformation characterized by the duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese family with PPD-II/III. We employ the refined IBD algorithm to identify the identity-by-decent (IBD) segments and compare the frequency among the patients and normal relatives. A total of 72 markers of 0.01 percentile of the permutation are identified as the peak signals. Among of them, 57markers locate on chromosome 7q36 which is associated with PPD. Further analyses refine the mapping of candidate region in chromosome 7q36 into two 380 Kb fragments within LMBR1 and SHH respectively. IBD approach is a suitable method for mapping cause gene of human disease. Target-enrichment sequencing as well as functional experiments are required to illustrate the pathogenic mechanisms for PPD in the future.

genetics↗

bioRxiv2017

Could The Recent Zika Epidemic Have Been Predicted?

Given knowledge at the time, the recent 2015-2016 zika virus (ZIKV) epidemic probably could not have been predicted. Without the prior knowledge of ZIKV being already present in South America, and given the lack of understanding of key epidemiologic processes and long-term records of ZIKV cases in the continent, the best related prediction was for potential risk of an Aedes-borne disease epidemic. Here we use a recently published two-vector capacity model to assess the predictability of the conditions conducive to epidemics of diseases like zika, chikungunya or dengue, transmitted by the independent or concurrent presence of Aedes aegypti and Aedes albopictus. We compare the potential risk of transmission forcing the model with the observed climate and with state-of-the-art operational forecasts from the North American Multi Model Ensemble (NMME), finding that the predictive skill of this new seasonal forecast system is highest for multiple countries in Latin America and the Caribbean during the December-February and March-May seasons, and slightly lower -but still of potential use to decision-makers- for the rest of the year. In particular, we find that above-normal suitable conditions for the occurrence of the zika epidemic at the beginning of 2015 could have been successfully predicted for several zika hotspots, and in particular for Northeast Brazil: the heart of the epidemic. Nonetheless, the initiation and spread of an epidemic depends on the effect of multiple factors beyond climate conditions, and thus this type of approach must be considered as a guide and not as a formal predictive tool of vector-borne epidemics.

epidemiology↗

bioRxiv2017

De Novo Annotation And Characterization Of The Translatome With Ribosome Profiling Data

By capturing and sequencing the RNA fragments protected by translating ribosomes, ribosome profiling sketches the landscape of translation at subcodon resolution. We developed a new method, RiboCode, which uses ribosome profiling data to assess the translation of each RNA transcript genome-wide. As shown by multiple tests with simulated data and cell type-specific QTI-seq and mass spectrometry data, RiboCode exhibits superior efficiency, sensitivity, and accuracy for de novo annotation of the translatome, which covers various types of novel ORFs in the previously annotated coding and non-coding regions and overlapping ORFs. Finally, to showcase its application, we applied RiboCode on a published ribosome profiling dataset and assembled the context-dependent translatomes of yeast under normal condition, heat shock, and oxidative stress. Comparisons among these translatomes revealed stress-activated novel upstream and downstream ORFs, some of which are associated with potential translational dysregulations of the main protein coding ORFs in response to the stress signals.

bioinformatics↗

bioRxiv2017

Cells With Treg-Specific FOXP3 Demethylation But Low CD25 Are Prevalent In Autoimmunity

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3+ cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells (here defined as CD25lowFOXP3+ T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+ T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs, including demethylation of the Treg-specific epigenetic control region in FOXP3 that is highly enriched in HELIOS+ cells, and lack of IL-2 production. As compared to conventional Tregs, more CD25lowFOXP3+HELIOS+ T cells are in cell cycle (33.0% vs 20.7% Ki-67+; P = 1.3 x 10-9) and express the late-stage inhibitory receptor PD-1 (67.2% vs 35.5%; P = 4.0 x 10-18), while having reduced expression of the early-stage inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and CD15s. The number of CD25lowFOXP3+ T cells are highly correlated (P = 1.2 x 10-19) with the proportion of CD25highFOXP3+ T cells in cell cycle (Ki-67+). These findings suggest that CD25lowFOXP3+ T cells represent a subset of Tregs that are derived from CD25highFOXP3+ T cells, and are a peripheral marker of recent Treg expansion in response to an autoimmune reaction in tissues.\n\nHighlights- FOXP3+ compartment within CD127lowCD25low T cells is expanded in autoimmune patients.\n\n- Increased numbers of CD25lowFOXP3+ T cells are a circulating marker of autoimmunity.\n\n- CD25lowFOXP3+ HELIOS+ T cells are fully demethylated at the FOXP3 TSDR.\n\n- CD25lowFOXP3+ T cells could represent a terminal stage of regulatory T cells.

immunology↗

bioRxiv2017

STAR-Fusion: Fast and Accurate Fusion Transcript Detection from RNA-Seq

MotivationFusion genes created by genomic rearrangements can be potent drivers of tumorigenesis. However, accurate identification of functionally fusion genes from genomic sequencing requires whole genome sequencing, since exonic sequencing alone is often insufficient. Transcriptome sequencing provides a direct, highly effective alternative for capturing molecular evidence of expressed fusions in the precision medicine pipeline, but current methods tend to be inefficient or insufficiently accurate, lacking in sensitivity or predicting large numbers of false positives. Here, we describe STAR-Fusion, a method that is both fast and accurate in identifying fusion transcripts from RNA-Seq data.\n\nResultsWe benchmarked STAR-Fusions fusion detection accuracy using both simulated and genuine Illumina paired-end RNA-Seq data, and show that it has superior performance compared to popular alternative fusion detection methods.\n\nAvailability and implementationSTAR-Fusion is implemented in Perl, freely available as open source software at http://star-fusion.github.io, and supported on Linux.\n\nContactbhaas@broadinstitute.org

bioinformatics↗

bioRxiv2017

Genotyping Of Zebrafish Embryos Fixed By Paraformaldehyde

The rapid generation of various species and strains of zebrafish using CRISPR/Cas9 technology has dramatically accelerated the interrogation of gene function in vivo. So far, several approaches for genotyping of unfixed genome-modified animals have been successfully developed, such as Surveyor assays, T7 endonuclease 1 (T7E1) assays, High Resolution Melt Analysis (HRMA) and PAGE-based genotyping approach. However, there is few published genotyping protocol for the embryos of lethal zebrafish mutants fixed by paraformaldehyde. We have designed this genotyping protocol so that it can be performed in a single step with reliable results. The protocol covers all steps to obtain the genotypes.

molecular biology↗

bioRxiv2016

Inference of Multiple-wave Admixtures by Length Distribution of Ancestral Tracks

The ancestral tracks in admixed genomes are of valuable information for population history inference. A few methods have been developed to infer admixture history based on ancestral tracks. Nonetheless, these methods suffered the same flaw that only population admixture history under some specific models can be inferred. In addition, the inference of history might be biased or even unreliable if the specific model is deviated from the real situation. To address this problem, we firstly proposed a general discrete admixture model to describe the admixture history with multiple ancestral populations and multiple-wave admixtures. We next deduced the length distribution of ancestral tracks under the general discrete admixture model. We further developed a new method, MultiWaver, to explore the multiple-wave admixture histories. Our method could automatically determine an optimal admixture model based on the length distribution of ancestral tracks, and estimate the corresponding parameters under this optimal model. Specifically, we used a likelihood ratio test (LRT) to determine the number of admixture waves, and implemented an expectation??maximization (EM) algorithm to estimate parameters. We used simulation studies to validate the reliability and effectiveness of our method. Finally, good performance was observed when our method was applied to real datasets of African Americans, Mexicans, Uyghurs, and Hazaras.

genetics↗