Biology subjects

Zhang, W.

Publications and source records attributed to Zhang, W..

At least 1,117 records · Page 62Linked to original sources

bioRxiv2017

Genome-wide homology analysis reveals new insights into the origin of the wheat B genome

Wheat is a typical allopolyploid with three homoeologous subgenomes (A, B, and D). The ancestors of the subgenomes A and D had been identified, but not for the subgenome B. The goatgrass Aegilops speltoides (genome SS) has been controversially considered a candidate for the ancestor of the wheat B genome. However, the relationship of the Ae. speltoides S genome with the wheat B genome remains largely obscure, which has puzzled the wheat research community for nearly a century. In the present study, the genome-wide homology analysis identified perceptible homology between wheat chromosome 1B and Ae. speltoides chromosome 1S, but not between other chromosomes in the B and S genomes. An Ae. speltoides-originated segment spanning a genomic region of approximately 10.46 Mb was identified on the long arm of wheat chromosome 1B (1BL). The Ae. speltoides-originated segment on 1BL was found to co-evolve with the rest of the B genome in wheat species. Thereby, we conclude that Ae. speltoides had been involved in the origin of the wheat B genome, but should not be considered an exclusive ancestor of this genome. The wheat B genome might have a polyphyletic origin with multiple ancestors involved, including Ae. speltoides. These novel findings provide significant insights into the origin and evolution of the wheat B genome, and will facilitate polyploid genome studies in wheat and other plants as well.

genetics↗

bioRxiv2017

Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli

Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further demonstrate that far-downstream mutations can also modulate mRNA levels by occluding the SD sequence through the formation of non-equilibrium secondary structures. By contrast, a non-endogenous RNA polymerase that decouples transcription and translation largely alleviates the effects of synonymous substitutions on mRNA levels. Finally, a complementary statistical analysis of the E. coli genome specifically implicates avoidance of intra-molecular base-pairing with the SD sequence. Our results provide general physical insights into the coding-level features that optimize protein expression in prokaryotes.

biophysics↗

bioRxiv2017

Aging Of Antiviral CD8+ Memory T Cells Fosters Increased Survival, Metabolic Adaptations And Lymphoid Tissue Homing

Aging of established antiviral T cell memory fosters a series of progressive adaptations that paradoxically improve rather than compromise protective CD8+T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8+ memory T cell (CD8+TM) homeostasis. Over time, CD8+TM become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8+TM quiescence and fitness but also impart the re-acquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8+TM from blood and nonlymphoid tissues to lymphatic organs results in CD8+TM accumulations in bone marrow, splenic white pulp and particularly lymph nodes. Altogether, these data demonstrate how temporal alterations of fundamental homeostatic determinants converge to render aged CD8+TM poised for greater recall responses.\n\nABBREVIATIONST cell subsets

immunology↗

bioRxiv2017

Clofazimine targets essential nucleoid associated protein, mycobacterial integration host factor (mIHF), in Mycobacterium tuberculosis

Clofazimine (CFZ) is a phenazine derivative used for treatment of leprosy, MDR-TB and XDR-TB. There is recent interest in understanding how CFZ works following the demonstration of its unique ability to shorten the treatment of MDR-TB. However, the target of CFZ in mycobacteria has remained elusive. Here, we show that CFZ binds to mycobacterial integration host factor (mIHF), which is an essential nucleoid associated protein in mycobacteria involved in DNA protection, chromosome organization and global gene regulation. We demonstrate that CFZ inhibits mIHF binding to DNA and interferes with mycobacterial gene expression. This mode of action is unique among all antibiotics including antimycibacterial agents and may help to explain its unusual action against Mycobacterium tuberculosis. Our study provides new insight about the mechanism of action of this intriguing drug and has implications for developing more effective treatment of TB.

microbiology↗

bioRxiv2017

Investigation of the role of a macromolecular complex of CFTR-NHERF2-LPA2 in the fluid hemostasis and inflammatory responses in intestinal epithelial cells

CFTR is a cAMP-regulated chloride channel located in the apical surface of intestinal epithelial cells; where it forms a macromolecular complex with NHERF2 and LPA2. CFTR has been shown to play a role in the pathogenies of several types of secretory diarrheas. Inflammatory bowel disease (IBD) is a chronic condition of intestine characterized by severe inflammation and mucosal destruction, genetic analysis has shown that LPA contribute to IBD and patients of cystic fibrosis also display the phenotype of diarrhea. The purpose of this study is to investigate if this complex plays a role in the inflammatory responses of intestinal epithelium.\n\nWe then explored the role of this complex in maintaining the integrity of tight junction and inflammatory responses in these cells. In vitro assays show that inhibiting CFTR or LPA2 in the intestinal epithelial cell could disrupt the epithelial cell junction, and reduce the TER of intestinal epithelial cells in both mouse and human cell line. EUSA assay show that intriguing LPA2 through LPS or LPA can increase the secretion of IL-8, while inhibiting or SiRNA knockdown of LPA2 can decrease the secretion of IL-8 in mouse or human intestinal epithelial cells. The CFTR inhibitor can reduce the IL-8 secretion in both mouse and human cell line, the deletion of CFTR in mouse intestine does not affect the IL-8 level, but the knockdown of CFTR in human cell line reduced the IL-8 protein level. The deletion of CFTR in human also reduced the IL-8 mRNA level. This indicates the CFTR-LPA complex is necessary for the expression of IL-8.

pathology↗

bioRxiv2017

A negative feedback mechanism in the insulin-regulated glucose homeostasis in Japanese flounder Paralichthys olivaceus by two ways of glucose administration

The present study comparatively analyzed the blood glucose and insulin concentration, the temporal and spatial expression of brain-gut peptides and the key enzymes of glycolysis and gluconeogenesis in Japanese flounder by intraperitoneal (IP) injection and oral (OR) administration of glucose. Samples were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48h after IP and OR, respectively. Results showed that the hyperglycemia lasted 5 hours and 21 hours in OR and IP group, respectively. The serum insulin concentration significantly decreased (1.58{+/-}0.21mIU/L) at 3h after IP glucose. However, it significantly increased at 3h (3.37{+/-}0.34mIU/L) after OR glucose. The gene expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and orexin precursor in the brain showed different profiles between the OR and IP group. The OR not IP administration of glucose had significant effects on the gene expressions of preprovasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and gastrin in the intestine. When the blood glucose concentration peaked in both IP and OR group, the glucokinase expression in liver was stimulated, but the expression of fructose-1,6-bisphosphatase was depressed. In conclusion, brain-gut peptides were confirmed in the present study. And the serum insulin and the brain-gut peptides have different responses between the IP and OR administration of glucose. A negative feedback mechanism in the insulin-regulated glucose homeostasis was suggested in Japanese flounder. Furthermore, this regulation could be conducted by activating PI3k-Akt, and then lead to the pathway downstream changes in glycolysis and gluconeogenesis.

biochemistry↗

bioRxiv2017

Evaluation of Topramezone on Zebrafish Retinoid Signaling

Topramezone is a highly selective herbicide developed for broadleaf and grass weeds control in corn. In this study, the effects of topramezone on zebrafish, especially in retinoid signaling were investigated. Zebrafish embryos were treated with topramezone from 4 hours post-fertilization (hpf) to 144 hpf. Exposed to topramezone significantly reduced the retinal and retinoic levels compared to controls. The transcriptional expression levels of retinol dehydrogenase (rdh1), retinoic acid receptor subunit (raraa), retinal dehydrogenase (raldh2), retinol binding protein (rbp1a), and cellular retinoic acid binding protein (crabp1a and crabp2a) were significantly decreased. Our results suggested that topramezone significantly impaired zebrafish retinoid signaling during a short time exposure. However, treatment with topramezone significantly increased the mRNA expression levels of zfblue, zfrho, zfgr1, zfuv, and zfred. Our data demonstrated that topramezone treatment could interrupt retinoid signaling and further affect zebrafish eye development.

molecular biology↗

bioRxiv2017

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

cancer biology↗

bioRxiv2017

5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages

5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof of principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.\n\nOne Sentence SummaryAnalyzing the epigenetic modification 5-hydroxymethylcysoine in circulating cell-free DNA reveals tumor tissue of origin and stages for cancer diagnostics.

genomics↗

bioRxiv2017

The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology

Pomegranate (Punica granatum L.) with an uncertain taxonomic status has an ancient cultivation history, and has become an emerging fruit due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the absence of genomic resources has restricted further elucidating genetics and evolution of these interesting traits. Here we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336 Mb genome, consists of 2,177 scaffolds with an N50 size of 1.7 Mb, and contains 30,903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis shares the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the color formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence represents the first reference in Lythraceae, providing an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding.

genomics↗

bioRxiv2017

A Bayesian Framework for Multiple Trait Colocalization from Summary Association Statistics

MotivationMost genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci.\n\nResultsWe applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes.\n\nAvailabilitymoloc is available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest.\n\nContactclaudia.giambartolomei@gmail.com\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

genomics↗

bioRxiv2017

The Molecular Genetic Basis of Herbivory between Butterflies and their Host-Plants

Interactions between herbivorous insects and their host-plants are a central component of terrestrial food webs and a critical topic in agriculture, where a substantial fraction of potential crop yield is lost annually to pests. Important insights into plant-insect interactions have come from research on specific plant defenses and insect detoxification mechanisms. Yet, much remains unknown about the molecular mechanisms that mediate plant-insect interactions. Here we use multiple genome-wide approaches to map the molecular basis of herbivory from both plant and insect perspectives, focusing on butterflies and their larval host-plants. Parallel genome-wide association studies in the Cabbage White butterfly, Pieris rapae, and its host-plant, Arabidopsis thaliana, pinpointed a small number of butterfly and plant genes that influenced herbivory. These genes, along with much of the genome, were regulated in a dynamic way over the time course of the feeding interaction. Comparative analyses, including diverse butterfly/plant systems, showed a variety of genome-wide responses to herbivory, yet a core set of highly conserved genes in butterflies as well as their host-plants. These results greatly expand our understanding of the genomic causes and evolutionary consequences of ecological interactions across two of Natures most diverse taxa, butterflies and flowering plants.

genomics↗

bioRxiv2017

Faster carbon accumulation in global forest soils

Comparing soil organic carbon (SOC) stocks across space and time is a fundamental issue in global ecology. However, the conventional approach fails to determine SOC stock in an equivalent volume of mineral-soil, and therefore, SOC stock changes can be under- or overestimates if soils swell or shrink during forest development or degradation. Here, we propose to estimate SOC stock as the product of mineral-soil mass in an equivalent mineral-soil volume and SOC concentration expressed as g C Kg-1 mineral-soil. This method enables researchers to compare SOC stocks across space and time. Our results show an unaccounted SOC accumulation of 2.4 - 10.1 g C m-2 year-1 in the 1m surface mineral-soils in global forests. This unaccounted SOC amounts to an additional C sink of 0.12 - 0.25 Pg C year-1, which equals 30 - 62% of the previously estimated annual SOC accumulation in global forests. This finding suggests that forest soils are stronger C sinks than previously recognized.

ecology↗

bioRxiv2017

The industrial anaerobe Clostridium acetobutylicum uses polyketides to regulate butanol production and differentiation

Polyketides are an important class of bioactive small molecules valued not only for their diverse therapeutic applications, but also for their role in controlling interesting biological phenotypes in their producing organisms. While numerous examples of polyketides derived from aerobic organisms exist, only a single family of polyketides has been identified from anaerobic organisms. Here we uncover a novel family of polyketides native to the anaerobic bacterium Clostridium acetobutylicum, an organism well-known for its historical use as an industrial producer of the organic solvents acetone, butanol, and ethanol. Through mutational analysis and chemical complementation assays, we demonstrate that these polyketides influence butanol production and act as chemical triggers of sporulation and granulose accumulation in this strain. This study represents a significant addition to the body of work demonstrating the existence and importance of polyketides in anaerobes, and showcases a novel strategy of manipulating the secondary metabolism of an organism to improve traits significant for industrial applications.

microbiology↗

bioRxiv2017

Attention is required for knowledge-based sequential grouping of syllables into words

How the brain sequentially groups sensory events into temporal chunks and how this process is modulated by attention are fundamental questions in cognitive neuroscience. Sequential grouping includes bottom-up primitive grouping and top-down knowledge-based grouping. In speech perception, grouping acoustic features into syllables can rely on bottom-up acoustic continuity cues but grouping syllables into words critically relies on the listeners lexical knowledge. This study investigates whether top-down attention is required to apply lexical knowledge to group syllables into words, by concurrently monitoring neural entrainment to syllables and words using electroencephalography (EEG). When attention is directed to a competing speech stream or cross-modally to a silent movie, neural entrainment to syllables is weakened but neural entrainment to words largely diminishes. These results strongly suggest that knowledge-based grouping of syllables into words requires top-down attention and is a bottleneck for the neural processing of unattended speech.

neuroscience↗

bioRxiv2017

Biosynthesis of Isonitrile Lipopeptides by Conserved Non-ribosomal Peptide Synthetase Gene Clusters in Actinobacteria

A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in intro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a new family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a non-heme iron(II)-dependent oxidase homologue, and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a non-ribosomal peptide synthetase (NRPS). In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.\n\nSignificance StatementMycobacterium tuberculosis is the leading causative agent of tuberculosis (TB), of which millions of deaths occur annually. A putative lipopeptide biosynthetic gene cluster has been shown to be essential for the survival of this pathogen in hosts, and homologous gene clusters have also been found in all pathogenic mycobacteria and other species of Actinobacteria. We have identified the function of these gene clusters in making a new family of isonitrile lipopeptides. The biosynthesis has several unique features, including an unprecedented mechanism for isonitrile synthesis. Our results have further suggested that these biosynthetic gene clusters play a role in metal transport, and thus have shed light on a new metal transport system that is crucial for virulence of pathogenic mycobacteria.

biochemistry↗

bioRxiv2017

Arabidopsis thaliana Trihelix Transcription factor AST1 mediates abiotic stress tolerance by binding to a novel AGAG-box and some GT motifs

Trihelix transcription factors are characterized by containing a conserved trihelix (helix-loop-helix-loop-helix) domain that bind to GT elements required for light response, play roles in light stress, and also in abiotic stress responses. However, only few of them have been functionally characterised. In the present study, we characterized the function of AST1 (Arabidopsis SIP1 clade Trihelix1) in response to abiotic stress. AST1 shows transcriptional activation activity, and its expression is induced by osmotic and salt stress. The genes regulated by AST1 were identified using qRT-PCR and transcriptome assays. A conserved sequence highly present in the promoters of genes regulated by AST1 was identified, which is bound by AST1, and termed AGAG-box with the sequence [A/G][G/A][A/T]GAGAG. Additionally, AST1 also binds to some GT motifs including GGTAATT, TACAGT, GGTAAAT and GGTAAA, but failed in binding to GTTAC and GGTTAA. Chromatin immunoprecipitation combined with qRT-PCR analysis suggested that AST1 binds to AGAG-box and/or some GT motifs to regulate the expression of stress tolerance genes, resulting in reduced reactive oxygen species, Na+ accumulation, stomatal apertures, lipid peroxidation, cell death and water loss rate, and increased proline content and reactive oxygen species scavenging capability. These physiological changes mediated by AST1 finally improve abiotic stress tolerance.

physiology↗

bioRxiv2017

A microbially derived tyrosine sulfated peptide mimics a plant peptide hormone

O_LIThe biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX functionally mimics the growth stimulating activity of PSY peptides.\nC_LIO_LIRoot length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analysis and Reactive Oxygen Species (ROS) burst assay to evaluate the activity of RaxX and PSY peptides.\nC_LIO_LIHere we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence.\nC_LIO_LIThese findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide.\nC_LI

plant biology↗