Biology subjects

Tian, J.

Publications and source records attributed to Tian, J..

5 recordsLinked to original sources

bioRxiv2018

Differential gene expression, including Sjfs800, in Schistosoma japonicum females before, during, and after male-female pairing

Schistosomiasis is a prevalent but neglected tropical disease caused by parasitic trematodes of the genus Schistosoma, with the primary disease-causing species being S. haematobium, S. mansoni, and S. japonicum. Male-female pairing of schistosomes is necessary for sexual maturity and the production of a large number of eggs, which are primarily responsible for schistosomiasis dissemination and pathology. Here, we used microarray hybridization, bioinformatics, quantitative PCR, in situ hybridization, and gene silencing assays to identify genes that play critical roles in S. japonicum reproduction biology, particularly in vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. Microarray hybridization analyses generated a comprehensive set of genes differentially transcribed before and after male-female pairing. Although the transcript profiles of females were similar 16 and 18 days after host infection, marked gene expression changes were observed at 24 days. The 30 most abundantly transcribed genes on day 24 included those associated with vitellarium development. Among these, genes for female-specific 800 (fs800), eggshell precursor protein, and superoxide dismutase (cu-zn-SOD) were substantially upregulated. Our in situ hybridization results in female S. japonicum indicated that cu-zn-SOD mRNA was highest in the ovary and vitellarium, eggshell precursor protein mRNA was expressed in the ovary, ootype, and vitellarium, and Sjfs800 mRNA was observed only in the vitellarium, localized in mature vitelline cells. Knocking down the Sjfs800 gene in female S. japonicum by approximately 60% reduced the number of mature vitelline cells, decreased rates of pairing and oviposition, and decreased the number of eggs produced in each male-female pairing by about 50%. These results indicate that Sjfs800 is essential for vitellarium development and egg production in S. japonicum and suggest that Sjfs800 regulation may provide a novel approach for the prevention or treatment of schistosomiasis.\n\nAuthor SummarySchistosomiasis is a common but largely unstudied tropical disease caused by parasitic trematodes of the genus Schistosoma. The eggs of schistosomes are responsible for schistosomiasis transmission and pathology, and the production of these eggs is dependent on the pairing of females and males. In this study, we determined which genes in Schistosoma japonicum females were differentially expressed before and after pairing with males, identifying the 30 most abundantly expressed of these genes. Among these 30 genes, we further characterized those in female S. japonicum that were upregulated after pairing and that were related to reproduction and vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. We identified three such genes, S. japonicum female-specific 800 (Sjfs800), eggshell precursor protein, and superoxide dismutase, and confirmed that the mRNAs for these genes were primarily localized in reproductive structures. By using gene silencing techniques to reduce the amount of Sjfs800 mRNA in females by about 60%, we determined that Sjfs800 plays a key role in development of the vitellarium and egg production. This finding suggests that regulation of Sjfs800 may provide a novel approach to reduce egg counts and thus aid in the prevention or treatment of schistosomiasis.

genomics↗

bioRxiv2018

Increased GITRL impairs the function of MDSCs and exacerbates primary Sjögren’s syndrome

It is largely unclear how MDSCs contribute to the development of primary Sjogrens syndrome (pSS). In experimental SS (ESS) mice, MDSCs were significantly increased but exhibited gradually diminished suppressive capacity during the disease progression. The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased with the development of pSS, and the increased GITRL was found to down-regulate the function of MDSCs while blocking GITR signal in MDSCs significantly restored their function and ameliorated ESS progression in mice. In pSS patients, expanded MDSCs expressed lower level of arginase were observed in patients with higher SSDAI. Moreover, the increased GITRL in serum was also found to closely correlate with the aberrant function of MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive capacity of MDSCs in pSS, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.

immunology↗

bioRxiv2017

An evidence-based approach to globally assess the covariate-dependent effect of MTHFR SNP rs1801133 on plasma homocysteine: a systematic review and meta-analysis

BackgroundThe single nucleotide polymorphism (SNP) of the gene Methylenetetrahydrofolate Reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for a rs1801133 carrier.\n\nObjectiveWe hypothesized that variability of this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers and/or confounders, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates.\n\nDesignWe systematically extracted from published studies the data of tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting meta-dataset was first used to analyze the covariates modifying effect by meta regression and other statistical means. Subsequently, we stratified tHcy data by the rs1801133 genotypes and analyzed under each genotype the variability of the risk resulted from the covariates confounding.\n\nResultsThe dataset contains data of 36 rs1801133 covariates that were collected from 114,448 subjects and 249 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification and, to a larger degree, confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner.\n\nConclusionswe demonstrated an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public that increasingly receives genetic data from commercial services without interpretation of its clinical relevance.

genetics↗

bioRxiv2017

Karyotype stability and unbiased fractionation in the paleo-allotetraploid Cucurbita genomes

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Interspecific hybrids between C. maxima and C. moschata are widely used as rootstocks for other cucurbit crops. We report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), and the allotetraploidization happened earlier than 3 Mya, when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization is uncommon in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima x C. moschata interspecific F1 hybrid and the two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into plant genome evolution and valuable resources for genetic improvement of cucurbit crops.

genomics↗

bioRxiv2016

Optimization of lag phase shapes the evolution of a bacterial enzyme

Mutations provide the variation that drives evolution, yet their effects on fitness remain poorly understood. Here we explore how mutations in the essential enzyme Adenylate Kinase (Adk) of E. coli affect multiple phases of population growth. We introduce a biophysical fitness landscape for these phases, showing how they depend on molecular and cellular properties of Adk. We find that Adk catalytic capacity in the cell (product of activity and abundance) is the major determinant of mutational fitness effects. We show that bacterial lag times are at a well-defined optimum with respect to Adks catalytic capacity, while exponential growth rates are only weakly affected by variation in Adk. Direct pairwise competitions between strains show how environmental conditions modulate the outcome of a competition where growth rates and lag times have a tradeoff, altogether shedding light on the multidimensional nature of fitness and its importance in the evolutionary optimization of enzymes.

evolutionary biology↗