Biology subjects

Jia, H.

Publications and source records attributed to Jia, H..

87 records · Page 5Linked to original sources

bioRxiv2019

The YdiU Domain Modulates Bacterial Stress Signaling through UMPylation

Sensing stressful conditions and adjusting cellular metabolism to adapt to the environment is essential for bacteria to survive in variable situations. Here, we describe a new stress-related protein YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine 5-monophosphate to a protein tyrosine/histidine residue--a novel modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+-binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. The detailed mechanism is proposed based on Apo-YdiU, YdiU-ATP, YdiU-AMP crystal structures and molecular dynamics simulation models of YdiU-UTP and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation. HighlightsO_LIYdiU involves in stress-resistance of Salmonella. C_LIO_LIYdiU mediates protein UMPylation in a Mn2+-dependent manner. C_LIO_LIStructural insights into YdiU-mediated UMPylation. C_LIO_LIUMPylation of chaperones by YdiU modulates their function. C_LI

biochemistry↗

bioRxiv2019

Shotgun Metagenomics of 361 elderly women reveals gut microbiome change in bone mass loss

Bone mass loss contributes to the risk of bone fracture in the elderly. Many factors including age, obesity, estrogen and diet, are associated with bone mass loss. Mice studies suggest that the intestinal microbiome might influence the bone mass by regulating the immune system, however there has been little evidence from human studies. We have recruited 361 Chinese elderly women to collect data for a metagenomic-wide association study (MWAS) to investigate the influence of the gut microbiome on bone health. Gut microbiome data were produced using BGISEQ500 sequencing, BMD was calculated using Hologic dual energy X-ray machine, BMI (Body Mass Index) and age were also provided. This therefore data allows exploration of gut microbiome diversity and links to bone mass loss, as well as microbial species and modules as markers for bone mineral density. Making these data potentially useful in studying the role the gut microbiota might play in bone mass loss and offering exploration into the bone mass loss process.

microbiology↗

bioRxiv2019

Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics

BackgroundThe gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.\n\nMethodWe used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naive type 2 diabetic (TN-T2D, n=77), pre-diabetic (Pre-DM, n=80), and normal glucose tolerant (NGT, n=97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naive T2D individuals to elucidate possible host-microbial interplays characterising different disease stages.\n\nFindingsWe observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D.\n\nInterpretationOur findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.\n\nFundingNational Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.

microbiology↗

bioRxiv2019

Biased Signaling: Distinct Ligand-directed Plasma Membrane Signalsomes Using a Common RGS/G Protein Core

Biased signaling occurs when different ligands that are directed at the same receptor launch different cellular outcomes. Because of their pharmacological importance, we know the most about biased ligands and little is known about other mechanisms to achieve signaling bias. In the canonical animal G protein system, endocytosis of a 7-transmembrane GPCR is mediated by arrestins to propagate or arrest cytoplasmic signaling depending on the bias. In Arabidopsis, GPCRs are not required for G protein coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the prototype 7-transmembrane Regulator of G Signaling 1 protein AtRGS1 modulates G signaling and through ligand-dependent endocytosis, de-repression of signaling is initiated but canonical arrestins are not involved. Endocytosis initiates from two separate pools of plasma membrane: sterol-dependent domains, possibly lipid rafts, and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and newly-discovered arrestin-like adaptors. Different trafficking origins and trajectories lead to different cellular outcomes. Thus, compartmentation with its attendant signalosome architecture is a previously unknown mechanism to drive biased signaling.

plant biology↗

bioRxiv2019

The Urinary Microbiota in Relation to the Reproductive Tract Microbiota

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. The potential link between female urine and reproductive tract microbial communities is currently not clear. Here we collected the urine samples from 147 Chinese women of reproductive age, and explored the nature of colonization by 16S rRNA gene amplicon sequencing, real-time qPCR and live bacteria culture. To demonstrate utility intra-individual Spearmans correlation was used to explore the relationship between urine and multi-sites of the reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Types of diverse, Streptococcus-dominated, and Lactobacillus-dominated were the three most common types in the cohort. Detailed comparison of the urinary microbiota to the multi-sites of reproductive tract microbiota demonstrated the urinary microbiota was more similar to the microbiota in the cervix and uterine cavity instead of vagina in the same women. Our data demonstrates the potential connectivity of the microbiota in the female urogenital system and provided insight into the exploration of urethra and genital tract diseases.

microbiology↗

bioRxiv2019

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

More than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.

microbiology↗

bioRxiv2019

The vagino-cervical microbiome as a woman's life history

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.

microbiology↗

bioRxiv2019

Heterologous expression of Stlac2, a laccase isozyme of Setosphearia turcica, and the ability of decolorization of malachite green

Laccases can catalyze monoelectronic oxidation and have shown to have an increasing value in industrial application. In this study, as identified by Native-PAGE and ESI-MS/MS, ascomycetous fungus Setosphaeria turcica produced three laccase isozymes: Stlac1, Stlac2, and Stlac6. Stlac2 was heterologously expressed in both eukaryotic and prokaryotic expression systems. The eukaryotic recombinant Stlac2 expressed in Pichia pastoris was inactive, and also showed a higher molecular weight than predicted because of glycosylation. The depression of laccase activity was attributable to the incorrect glycosylation at Asn97. Stlac2 expressed in Escherichia coli and after being renaturated from the inclusion body, the recombinant Stlac2 exhibited activity of 28.23 U/mg with 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. The highest activity was observed at pH of 4.5 and the temperature of 60 {degrees}C. The activity of recombinant Stlac2 was inhibited by 10 mM Na+, Mg2+, Ca2+, Mn2+, and increased by 10 mM of Fe3+ with a relatively activity of 315% compared with no addition. Cu2+ did not affect enzyme activity. Recombinant Stlac2 was capable of decolorizing 67.08% of 20 mg/L malachite green in 15 min without any mediators. It is suggested that Stlac2 has potential industrial applications. ImportanceSetosphaeria turcica, an ascomycetous fungus causes northern corn leaf blight, product three laccase isozymes identified by Native-PAGE and ESI-MS/MS. The major expression laccase gene StLAC2 was expression in both eukaryotic and prokaryotic expression systems, which found incorrect glycosylation at Asn97 may result in the depression of laccase activity. The heterologous laccase Stlac2 decolorize organic dye malachite green, which had a potential industrial application.

bioengineering↗

bioRxiv2019

MATRIEX Imaging: Multi-Area Two-photon Real-time In-vivo Explorer

Two-photon laser scanning microscopy, originally developed since 1990s1, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo2. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel multi-axis optical conjugation method that enables two-photon imaging at single-cell resolution simultaneously in multiple areas at different depths, each of which could have a view diameter of ~200 m and could be largely freely targeted within a zone up to 12-mm diameter. For example, we show simultaneous imaging of neuronal activities in the primary visual cortex (V1), the primary motor cortex (M1) and the hippocampal CA1 region of awake mice. This method can be readily implemented on a single conventional two-photon microscope to enable multi-area exploration of neuronal activities in vivo.

neuroscience↗

bioRxiv2018

Bacterial strain displacement in inflammatory bowel diseases after fecal microbiota transplantation

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has recently been used to treat inflammatory bowel disease (IBD). To elucidate the extent and principles of microbiota engraftment in IBD patients after FMT treatment, we conducted an interventional prospective cohort study. The cohort included two categories of patients: (1) patients with moderate to severe Crohns disease (CD) (Harvey-Bradshaw Index [≥] 7, n = 11, and (2) patients with ulcerative colitis (UC) (Montreal classification, S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples of the participants were collected along with their clinical metadata. For comparative analysis, 10 fecal samples from 10 healthy people were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent natural microbiota shifts during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as the most contributive factors for prediction accuracy.

clinical trials↗

bioRxiv2018

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

ImportanceAlthough a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE by large-scale sequencing data.\n\nObjectiveTo identify the genetic variants that caused MACE.\n\nDesignAll patients in this study were allocated to dual antiplatelet therapy for up to 12 months and have the follow-up duration of 18 months.\n\nSettingA two-stage association study was performed.\n\nParticipantsWe evaluated the associations of genetic variants and MACE in 1961 patients with ACS undergoing PCI (2009-2012), including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort.\n\nMain Outcomes and MeasureThe primary clinical efficacy endpoint was the major adverse cardiovascular events (MACE) composite endpoint, including cardiovascular death, myocardial infarction (MI), stroke (CT or MR scan confirmed) and repeated revascularization (RR).\n\nResultsWe discovered and confirmed six new genotypes associated with MACE in patients with ACS. Of which, rs17064642 at MYOM2 increased the risk of MACE (hazard ratio [HR] 2.76; P = 2.95 x 10-9) and reached genome-wide significance. The other five suggestive variants were KRTAP10-4 (rs201441480), WDR24 (rs11640115), ECHS1 (rs140410716), AGAP3 (rs75750968) and NECAB1 (rs74569896). Notably, the expressions of MYOM2 and ECHS1 are down-regulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting MACE and achieved high predictive accuracy (0.809).\n\nConclusions and RelevanceWe identified six new genotypes associated with MACE and developed a superior classifier for predicting MACE. Our findings shed light on the pathogenesis of cardiovascular outcomes and may help clinician to make decision on the therapeutic intervention for ACS patients.\n\nTrial RegistrationThis study has been registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, Registration number: ChiCTR-OCH-11001198).

genetics↗

bioRxiv2018

Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the real or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQ1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 x 10-36, OR=2.29). Further stepwise conditional analysis revealed that DR{beta}1:37N has an independent protective effect on ACPA-positive RA (P = 5.81 x 10-16, OR=0.49). The DQ1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 x 10-5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQ1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DR{beta}1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.\n\nIn this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.

genetics↗

bioRxiv2018

MetaPGN: a pipeline for construction and graphical visualization of annotated pangenome networks

Pangenome analyses facilitate the interpretation of genetic diversity and evolutionary history of a taxon. However, there is an urgent and unmet need to develop new tools for advanced pangenome construction and visualization, especially for metagenomic data. Here we present an integrated pipeline, named MetaPGN, for construction and graphical visualization of pangenome network from either microbial genomes or metagenomes. Given either isolated genomes or metagenomic assemblies coupled with a reference genome of the targeted taxon, MetaPGN generates a pangenome in a topological network, consisting of genes (nodes) and gene-gene genomic adjacencies (edges) of which biological information can be easily updated and retrieved. MetaPGN also includes a self-developed Cytoscape plugin for layout of and interaction with the resulting pangenome network, providing an intuitive and interactive interface for full exploration of genetic diversity. We demonstrate the utility of MetaPGN by constructing Escherichia coli (E. coli) pangenome networks from five E. coli pathogenic strains and 760 human gut microbiomes respectively, revealing extensive genetic diversity of E. coli within both isolates and gut microbial populations. With the ability to extract and visualize gene contents and gene-gene physical adjacencies of a specific taxon from large-scale metagenomic data, MetaPGN provides advantages in expanding pangenome analysis to uncultured microbial taxa. MetaPGN is available at https://github.com/peng-ye/MetaPGN.

genomics↗

bioRxiv2018

Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton

Ciliary and rhabdomeric photoreceptor cells represent two main lines of photoreceptor evolution in animals. The two photoreceptor-cell types coexist in some animals, however how they functionally integrate is unknown. We used connectomics to map synaptic paths between ciliary and rhabdomeric photoreceptors in the planktonic larva of the annelid Platynereis and found that ciliary photoreceptors are presynaptic to the rhabdomeric circuit. The behaviors mediated by the ciliary and rhabdomeric cells also interact hierarchically. The ciliary photoreceptors are UV-sensitive and mediate downward swimming to non-directional UV light, a behavior absent in ciliary-opsin knockouts. UV avoidance antagonizes positive phototaxis mediated by the rhabdomeric eyes so that vertical swimming direction is determined by the ratio of blue/UV light. Since this ratio increases with depth, Platynereis larvae may use it as a depth gauge during planktonic migration. Our results revealed a functional integration of ciliary and rhabdomeric photoreceptors with implications for eye and photoreceptor evolution.

neuroscience↗

bioRxiv2017

Secretogranin-II Plays A Critical Role In Zebrafish Neurovascular Modeling

Summary statementNeurons expressing sgIIb align with central arteries in hindbrain. We show that sgIIb is critical for neurovascular modeling the larval zebrafish mediated by MAPK and PI3K/AKT signaling in vivo.\n\nAbstractSecretoneurin (SN) is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II (SgII). In zebrafish and other teleosts there are 2 paralogs we previously named sgIIa and sgIIb. Our results showed that neurons expressing sgIIb were aligned with central arteries in hindbrain, demonstrating a close neurovascular association. Both sgIIb-/- and sgIIa-/- /sgIIb-/- mutant embryos were defective in hindbrain central artery development, while artery development in sgIIa-/- mutant embryos was not affected. Hindbrain arterial and venous network identities were not affected in sgIIb-/- mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways were inhibited in sgIIb-/- mutant embryos. Injection of a synthetic SNb mRNA or delivery of the protein kinase activator N-arachidonoyl-L-serine could partially rescue the central artery developmental defects in the sgIIb mutants. This study provides the first in vivo evidence that sgIIb plays a critical role in neurovascular modeling the hindbrain.

developmental biology↗