Biology subjects

Yuan, Z.

Publications and source records attributed to Yuan, Z..

11 recordsLinked to original sources

bioRxiv2018

Longitudinal Visual Analytics for Unpacking the Cancer Journey

Retrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often based on factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. We discuss qualitative inquiry into user tasks and goals, data elements and models resulting in an innovative natural language processing pipeline and a visual analytics tool designed to facilitate interpretation of patient summaries and identification of cohorts for retrospective research.

cancer biology↗

bioRxiv2018

Altered microRNA expression profles are involved in Storage Lesions of Apheresis Platelet

Although platelet is anucleate cell, it contains a large amount miRNAs. This study aims to explore the relationship between miRNAs expression profles and platelets function, as well as miRNAs potential roles during platelet storage lesions. Platelets were collected from 15 healthy men with O blood types. MiRNAs profiles in platelets were detected by Agilent Human miRNA Array Differential miRNA levels were studied using human platelets after apheresis and stored for 2, 5 and 8 days using microarray. There were 167 and 230 altered miRNAs during the 5 and 8 day storage, respectively. In addition, the number of reduced miRNAs was much greater than that of increased. And many of them are involved in functions of platelet activation, degranulation, PDGF receptor signaling pathway and cell differentiation. The results of RT-PCR showed that the expression of miR-21-5p, miR-21-3p and miR-155 decreased on the 5th day, while miR-223, miR-3162 and let-7b increased. Flow cytometry results revealed that with increase of storage time, the expression of P2Y12 increased and phosphorylation level of VASP reduced. Meanwhile, the platelet reactivity index (PRI) decreased from 72.7% to 18.2%, while the apoptotic percentage of platelet significantly increased. For the first time, we found altered miRNAs are closely related to platelet aggregation, including P2Y12, VASP and GPb/a. Through KEGG database prediction, we verified there were many miRNAs impacting the pathway of platelet aggregation, such as miR-223, miR-21 and let-7b, which indicated miRNAs might serve as potential biomarkers of storage lesion in platelet. These target miRNAs are related to activation, degranulation and PDGF receptor signaling pathway of platelet.

molecular biology↗

bioRxiv2018

Regulatory networks of gene expression in maize (Zea mays) under drought stress and re-watering

Drought can severely limit plant growth and production. However, few studies have investigated gene expression profiles in maize during drought/re-watering. We compared drought-treated and water-sufficient maize plants by measuring their leaf relative water content, superoxide dismutase and peroxidase activities, proline content, and leaf gas exchange parameters (photosynthetic rates, stomatal conductance, and transpiration rates). We conducted RNA sequencing analyses to elucidate gene expression profiles and identify miRNAs that might be related to drought resistance. A GO enrichment analysis showed that the common DEGs (differently expressed genes) between drought-treated and control plants were involved in response to stimulus, cellular process, metabolic process, cell part, and binding and catalytic activity. Analyses of gene expression profiles revealed that 26 of the DEGs under drought encoded 10 enzymes involved in proline synthesis, suggesting that increased proline synthesis was a key part of the drought response. We also investigated cell wall-related genes and transcription factors regulating abscisic acid-dependent and -independent pathways. The expression profiles of the miRNAs miR6214-3p, miR5072-3p, zma-miR529-5p, zma-miR167e-5p, zma-miR167f-5p, and zma-miR167j-5p and their relevant targets under drought conditions were analyzed. These results provide new insights into the molecular mechanisms of drought tolerance, and may identify new targets for breeding drought-tolerant maize lines.\n\nAbbreviationsleaf relative water content: RWC, superoxide dismutase activity: SOD, peroxidase activity: POD, proline content: Pro, photosynthetic rates: Pn, stomatal conductance: Cond, transpiration rates: Tr.; quantitative real-time polymerase chain reaction: qPCR; abscisic acid; ABA; polyethylene glycol :PEG; Principal component analysis :PCA; polyacrylamide gel electrophoresis :PAGE\n\nHighlightThe study of physiology and molecular mechanism of maize laid a theoretical foundation for drought resistance breeding under drought stress and re-watering.

genomics↗

bioRxiv2018

Hepatitis C virus NS5A inhibitor daclatasvir allosterically impairs NS4B-involved protein-protein interactions within the viral replicase and disrupts the replicase quaternary structure in a replicase assembly surrogate system

Daclatasvir (DCV) is a highly potent direct-acting antiviral that targets the non-structural protein 5A (NS5A) of hepatitis C virus (HCV) and has achieved great clinical successes. Previous studies demonstrate its impact on the viral replication complex assembly. However the precise mechanism by which DCV impairs the replication complex assembly remains elusive. In this study, by using HCV subgenomic replicons and a viral replicase assembly surrogate system that expresses the HCV NS3-5B polyprotein to mimic the viral replicase assembly, we dissected the impacts of DCV on aggregation and tertiary structure of NS5A, the protein-protein interactions within the viral replicase and the quaternary structure of the viral replicase. We found that DCV didnt affect aggregation and tertiary structure of NS5A. DCV induced a quaternary structural change of the viral replicase, evidenced by selectively increasing of the NS4Bs sensitivity to proteinase K digestion. Mechanically, DCV impaired the NS4B-involved protein-protein interactions within the viral replicase. The DCV-resistant mutant Y93H was refractory to the DCV-induced reduction of the NS4B-invoved protein interactions and the quaternary structural change of the viral replicase. In addition, Y93H reduced NS4B-involed protein-protein interactions within the viral replicase and attenuated viral replication. We propose that DCV may induce a position change of NS5A, which allosterically affects the protein interactions within the replicase components and disrupts the replicase assembly.\n\nImportanceThe development of the direct-acting antivirals (DAA) has resulted in great clinical achievements for Hepatitis C Virus (HCV) treatment. Daclatasvir (DCV) is an inhibitor targeting the non-enzymatic NS5A, with the 50% effective concentration values in the picomolar range. Accumulated data suggest that DCV blocks the biogenesis of the HCV replication complex. However the mechanistic actions of DCV are still largely unknown. Insights into the action mechanism of DCV on the viral replication complex assembly of HCV may enlighten the development of next generation of DAAs and new anti-viral strategies for other positive-strand RNA viruses for which there are a scarcity of DAAs. Herein, using HCV subgenomic replicons and a viral replicase assembly surrogate system, we dissected the mechanistic actions of DCV on the viral replicase assembly. We found that DCV allosterically impairs NS4B-involved protein-protein interactions within the viral replicase and disrupts the quaternary structure of the viral replicase.

microbiology↗

bioRxiv2018

Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients

Extracellular HBV RNA has been detected in both HBV-replicating cell culture media and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition remain controversial. Here, we demonstrated that extracellular HBV RNA species were of heterogeneous lengths, ranging from the length of pregenomic RNA to a few hundred nucleotides. In cell models, these RNAs were predominantly associated with naked capsids although virions also harbored a minority of them. Moreover, HBV RNAs in hepatitis B patients blood circulation were localized in unenveloped capsids in the form of capsid-antibody-complexes (CACs) and in virions. Furthermore, we showed that extracellular HBV RNAs could serve as template for viral DNA synthesis. In conclusion, extracellular HBV RNAs mainly consist of pgRNA or the pgRNA species degraded by the RNase H domain of the polymerase in the process of viral DNA synthesis and circulate as CACs and virions. Their presence in the blood circulation of CHB patients may be exploited to develop novel biomarkers for HBV persistence.

microbiology↗

bioRxiv2018

Structural and functional studies of the RBPJ-SHARP complex reveal conserved corepressor binding site

The Notch pathway is a conserved signaling mechanism that is essential for cell fate decisions during pre and postnatal development. Dysregulated signaling underlies the pathophysiology of numerous human diseases, most notably T-cell acute lymphoblastic leukemia. Receptor-ligand interactions result in changes in gene expression, which are regulated by the transcription factor CSL. CSL forms a complex with the intracellular domain of the Notch receptor and the transcriptional coactivator Mastermind, which is required to activate transcription of all Notch target genes. CSL can also function as repressor by interacting with corepressor proteins, e.g. SHARP in mammals and Hairless in Drosophila melanogaster; however, its role as a transcriptional repressor is not well understood. Here we determine the high-resolution structure of RBPJ, the mouse CSL ortholog, bound to the corepressor SHARP and DNA, which reveals a new mode of corepressor binding to CSL and an interesting example for how ligand binding sites evolve in proteins. Based on the structure, we designed and tested a number of mutants in biophysical, biochemical, and cellular assays to characterize the role of RBPJ as a repressor of Notch target genes. Our cellular studies clearly demonstrate that RBPJ mutants that are deficient for binding SHARP are incapable of repressing transcription from genes responsive to Notch signaling. Altogether, our structure-function studies of the RBPJ-SHARP corepressor complex bound to DNA provide significant insights into the repressor function of RBPJ and identify a new binding pocket on RBPJ that could be targeted for therapeutic benefit.

biochemistry↗

bioRxiv2018

Exosomes exploit the virus entry machinery and pathway to transmit IFN-α-induced antiviral activity.

Interferon- (IFN-) induces the transfer of resistance to hepatitis B virus (HBV) from liver nonparenchymal cells (LNPCs) to hepatocytes via exosomes. However, little is known about the entry machinery and pathway involved in the transmission of IFN--induced antiviral activity. Here, we found that macrophage exosomes depend on T cell immunoglobulin and mucin receptor 1 (TIM-1), a hepatitis A virus (HAV) receptor, to enter hepatocytes for delivering IFN--induced anti-HBV activity. Moreover, two primary endocytic routes for virus infection, clathrin-mediated endocytosis (CME) and macropinocytosis, collaborate to permit exosome entry and anti-HBV activity transfer. Subsequently, lysobisphosphatidic acid (LBPA), an anionic lipid closely related to endosome penetration of virus, facilitates membrane fusion of exosomes in late endosomes/ multivesicular bodies (LEs/MVBs) and the accompanying exosomal cargo uncoating. Together, this study provides comprehensive insights into the transmission route of macrophage exosomes to efficiently deliver IFN--induced anti-HBV activity and highlights the similarities between the entry mechanisms of exosomes and virus.\n\nImportanceOur previous study showed that LNPC-derived exosomes could transmit IFN--induced antiviral activity to HBV replicating hepatocytes, but the concrete transmission mechanisms which include exosome entry and exosomal cargo release remain unclear. In this study, we found that virus entry machinery and pathway were also applied to exosome-mediated cell-to-cell antiviral activity transfer. Macrophage-derived exosomes exploit hepatitis A virus receptor for access to hepatocytes. Later, CME and macropinocytosis are utilized by exosomes which is followed by exosome-endosome fusion for efficient transfer of IFN--induced anti-HBV activity. Dissecting the similarities between exosome and virus entry will be beneficial to designing exosomes as efficient vehicles for antiviral therapy.

microbiology↗

bioRxiv2018

Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation

Antibiotic resistance poses a major threat to public health. Overuse and misuse of antibiotics are generally recognised as the key factors contributing to antibiotic resistance. However, whether non-antibiotic, anti-microbial (NAAM) chemicals can directly induce antibiotic resistance is unclear. We aim to investigate whether the exposure to a NAAM chemical triclosan (TCS) has an impact on inducing antibiotic resistance on Escherichia coli. Here, we report that at a concentration of 0.2 mg/L TCS induces multi-drug resistance in wild-type Escherichia coli after 30-day TCS exposure. The oxidative stress induced by TCS caused genetic mutations in genes such as fabI, frdD, marR, acrR and soxR, and subsequent up-regulation of the transcription of genes encoding beta-lactamase and multi-drug efflux pump, together with down-regulation of genes related to membrane permeability. The findings advance our understanding of the potential role of NAAM chemicals in the dissemination of antibiotic resistance in microbes, and highlights the need for controlling biocide applications.

microbiology↗

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 mouse model of necrotic biliary pancreatitis induced by combining gallstone formation and ligation of the biliary-pancreatic duct

ObjectiveThe aim of the present investigation is to develop a mouse model of biliary pancreatitis with characteristics of both gallstone formation and pancreatitis, mimicking the human etiology and pathphysiological character.\n\nDesignMale C57BL/6 mice were fed with chow, high fat/cholesterol and lithogenic diet for 12 weeks respectively. Laparotomy was done followed by ligation of pancreatic duct (PD), bile duct and pancreatic duct (BPD), or sham operation.\n\nResultsLittle or no evidence of pancreatitis was observed in PD group of mice fed with chow or high fat/cholesterol diet, or in the tail of pancreata removed from animals fed with lithogenic diet. In the head of pancreas, pancreas damage was dramatically more severe in the lithogenic group. When bile reflux was blocked by BPD, pancreas damage markedly reduced to level of chow diet group. The lithogenic diet group also developed significantly more severe multi organ dysfunction syndrome (MODS) in the lung, kidney and liver. The severity of pancreatitis is associated with persistent high bile level of cholesterol and bile acid after obstruction of the biliary-pancreatic duct. Cholesterol crystal aggravated injury of pancreatic acinar cells caused by taurocholate. After obstruction of the biliary-pancreatic duct, in the lithogenic diet group, liver Abcg8 and Cyp7a1 was up-regulated, compared to the control group.\n\nConclusionWe developed a mouse model of severe biliary pancreatitis in both local pancreas damage and MODS. This model provides a sound explanation for the Opie theory dilemma and a potential therapeutical direction in clinical practice as well.\n\nSummary statementA biliary pancreatitis has characters of both gallstone and pancreatitis, mimicking human etiology and pathophysiology, which gave a clear answer to the long time Opie theory dilemma.

pathology↗

bioRxiv2016

The Monarch Initiative: Insights across species reveal human disease mechanisms

The principles of genetics apply across the whole tree of life: on a cellular level, we share mechanisms with species from which we diverged millions or even billions of years ago. We can exploit this common ancestry at the level of sequences, but also in terms of observable outcomes (phenotypes), to learn more about health and disease for humans and all other species. Applying the range of available knowledge to solve challenging disease problems requires unified data relating genomics, phenotypes, and disease; it also requires computational tools that leverage these multimodal data to inform interpretations by geneticists and to suggest experiments. However, the distribution and heterogeneity of databases is a major impediment: databases tend to focus either on a single data type across species, or on single species across data types. Although each database provides rich, high-quality information, no single one provides unified data that is comprehensive across species, biological scales, and data types. Without a big-picture view of the data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) is an international consortium dedicated to providing computational tools that leverage a computational representation of phenotypic data for genotype-phenotype analysis, genomic diagnostics, and precision medicine on the basis of a large-scale platform of multimodal data that is deeply integrated across species and covering broad areas of disease.

evolutionary biology↗