Biology subjects

Yue, W.

Publications and source records attributed to Yue, W..

4 recordsLinked to original sources

bioRxiv2018

Tissue-expression profiles unveils the gene interaction of hepatopancreas, eyestalk, and ovary in precocious female Chinese mitten crab, Eriocheir sinensis

Sexual precocity is a serious and common biological phenomenon in animal species. Large amount of precocity individuals was identified in Chinese mitten crab, Eriocheir sinensis, which caused huge economical loss every year. However, the underlying genetic basis of precocity in E. sinensis is still lack. In this study, histology observation, comparative transcriptome was conducted among different stages of precocious one-year old and normal two-year old E. sinensis, tissue-expression profiles of ovary, hepatopancreas, and eyestalk tissues were presented and compared. Genes associated with lipid metabolic process, lipid transport, vitelline membrane formation, vitelline synthesis and neuropeptide hormone related genes were upregulated in the ovary, hepatopancreas and eyestalk of precocious E. sinensis. Our results indicated eyestalk involved in neuroendocrine system providing neuropeptide hormone that may induce vitellogenesis in hepatopancreas and further stimulate ovary development. Hepatopancreas is a site for energy storage, vitellogenin synthesis and may assist to induce oogenesis through lipid transport in precocious E. sinensis. The genetic basis of precocity in E. sinensis is an integrated gene regulatory network of eyestalk, hepatopancreas, and ovary tissues. Our study provides effective convenient phenotype measurement method for identification of potential precocious E. sinensis detection, and valuable genetic resources and novel insights into the research of molecular mechanism of precocity in E. sinensis.

bioinformatics↗

bioRxiv2018

Structural basis of human 5,10-methylenetetrahydrofolate reductase (MTHFR) regulation by phosphorylation and S-adenosylmethionine inhibition

The folate and methionine cycles are crucial to the biosynthesis of lipids, nucleotides and proteins, and production of the global methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 [A] resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of novel fold provides the predominant interface for MTHFR homo-dimerization, positioning the N-terminal serine-rich phosphorylation region into proximity with the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16-total), increases sensitivity to SAM binding and inhibition. Finally, we demonstrate the 25-amino-acid inter-domain linker enables conformational plasticity and propose it to be a key mediator of SAM regulation.

biochemistry↗

bioRxiv2018

Zinc(II) binding on human wild-type ISCU and Met140 variants modulates Fe-S complex activity

The human de novo iron-sulfur (Fe-S) assembly complex consists of the cysteine desulfurase NFS1, accessory protein ISD11, scaffold protein ISCU, and allosteric activator frataxin (FXN). FXN has been shown to bind the NFS1-ISD11-ISCU complex (SDU), to activate the desulfurase activity and thus Fe-S cluster biosynthesis. Conversely, in the absence of FXN, the NFS1-ISD11 (SD) complex was reported to be inhibited by the binding of recombinant ISCU. Here, we show that recombinant ISCU binds zinc(II) ion, and that the presence of zinc in as-isolated ISCU has impacts on the SDU desulfurase activity as measured by sulfide production. Indeed, the removal of this zinc(II) ion from ISCU causes a moderate but significant increase in activity compared to SD alone, and FXN can activate both zinc-depleted and zinc-bound forms of ISCU complexed to SD. Recent yeast studies have reported a substitution on the yeast ISCU orthologue Isu, at position Met141 (Met140 in human numbering of precursor protein) to Ile, Leu, Val, or Cys that could bypass the requirement of FXN for Fe-S cluster assembly and cell viability. Using recombinant human proteins, we report no significant differences in the biochemical and biophysical properties observed between wild-type and variants M140I, M140 L, and M140 V of ISCU. Importantly, in the absence of FXN, ISCU variants behaved like wild-type and did not stimulate the desulfurase activity of the SD complex. This study therefore identifies an important regulatory role for ISCU-bound zinc in modulation of the human Fe-S assembly system in vitro but no FXN bypass effect on mutations at position Met140 in human ISCU.\n\nABBREVIATIONS

biochemistry↗

bioRxiv2018

Structural and functional influences of urban and rural childhoods on the medial prefrontal cortex

Global increases in urbanization have brought dramatic economic, environmental and social changes. However, less is understood about how these may influence disease-related brain mechanisms underlying epidemiological observations that urban birth and childhoods may increase the risk for neuropsychiatric disorders, including increased social stress and depression. In a genetically homogeneous Han Chinese adult population with divergent urban and rural birth and childhoods, we examined the structural and functional MRI neural correlates of childhood urbanicity, focusing on behavioral traits responding to social status threats, and polygenic risk for depression. Subjects with divergent rural and urban childhoods were similar in adult socioeconomic status and were genetically homogeneous. Urban childhoods, however, were associated with higher trait anxiety-depression. On structural MRI, urban childhoods were associated with relatively reduced medial prefrontal gray matter volumes. Functional medial prefrontal engagement under social status threat during working memory correlated with trait anxiety-depression in subjects with urban childhoods, to a significantly greater extent than in their rural counterparts, implicating an exaggerated physiological response to the threat context. Stress-associated medial prefrontal engagement also interacted with polygenic risk for depression, significantly predicting a differential response in individuals with urban but not rural childhoods. Developmental urbanicity thus differentially influenced medial prefrontal structure and function, at least in part through mechanisms associated with the neural processing of social status threat, trait anxiety, and genetic risk for depression, which may be factors in the association of urbanicity with adult psychopathology.\n\nSignificance StatementUrban living has been associated with social inequalities and stress. However, less is understood about the neural underpinnings by which these stressors affect disease risk, and in particular, genetic risk for depression. Leveraging urbanization in China, we studied adults with diverse urban and rural upbringings, who were genetically homogeneous and with similar current socioeconomic status, to isolate the effects of childhood urbanicity. At medial prefrontal cortex, a region critical for processing emotional stressors and social status, genetic risk for depression resulted in more deleterious function under stress in individuals with urban, but not rural childhoods. This implicates medial prefrontal cortexs critical role in brain development, integrating genetic mechanisms of stress and depression with the childhood environment.

neuroscience↗