Biology subjects

Gong, X.

Publications and source records attributed to Gong, X..

8 recordsLinked to original sources

bioRxiv2018

Individual variations of the human corticospinal tract and its hand-related motor fibers using diffusion MRI tractography

The corticospinal tract (CST) is one of the most well-studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we proposed a novel method, using manually-drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heatmaps from 37 subjects for both the aforementioned tracts, which could be utilized as reference for clinicians to explore neuropathology in both trauma and disease states.

neuroscience↗

bioRxiv2018

Different SUMO Paralogs Determine the Fate of WT and Mutant CFTRs: Biogenesis vs. Degradation

A pathway for CFTR degradation is initiated by Hsp27 which cooperates with Ubc9 and binds to the common F508del mutant to modify it with SUMO-2/3. These SUMO paralogs form poly-chains, which are recognized by the ubiquitin ligase, RNF4, for proteosomal degradation. Here, protein array analysis identified the SUMO E3, PIAS4, which increased WT and F508del CFTR biogenesis in CFBE airway cells. PIAS4 increased immature CFTR three-fold and doubled expression of mature CFTR, detected by biochemical and functional assays. In cycloheximide chase assays, PIAS4 slowed immature F508del degradation 3-fold and stabilized mature WT CFTR at the PM. PIAS4 knockdown reduced WT and F508del CFTR expression by 40-50%, suggesting a physiological role in CFTR biogenesis. PIAS4 modified F508del CFTR with SUMO-1 in vivo and reduced its conjugation to SUMO-2/3. These SUMO paralog specific effects of PIAS4 were reproduced in vitro using purified F508del NBD1 and SUMOylation reaction components. PIAS4 reduced endogenous ubiquitin conjugation to F508del CFTR by ~50%, and blocked the impact of RNF4 on mutant CFTR disposal. These findings indicate that different SUMO paralogs determine the fates of WT and mutant CFTRs, and they suggest that a paralog switch during biogenesis can direct these proteins to different outcomes: biogenesis vs. degradation.

cell biology↗

bioRxiv2018

MECP2 duplication and mutations impair NSCs differentiation via miR-197 regulated ADAM10

How MECP2 (Methyl-CpG-binding protein 2) duplication affects cortex development remains elusive. We found that elevated MeCP2 expression promotes neurogenesis during cortex development in Tg(MECP2) mouse brain. Ectopic expression of MeCP2 in NPCs inhibits ADAM10 and hence compromises the NOTCH pathway during NPC differentiation. MeCP2 up-regulates miR-197 to down-regulate ADAM10. The enhanced NPC differentiation/migration in Tg(MECP2) embryonic brain can be repressed by overexpression of ADAM10 or a miR-197 inhibitor.\n\nConsistently, the reduced neurogenesis induced by three rare MeCP2 missense mutations (H371R, E394K, G428S) identified in a Han Chinese autism spectrum disorders (ASD) cohort, can be reversed by miR-197 both in vitro and in vivo. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for neurogenesis, which is affected by both MeCP2 duplication and mutation.

developmental biology↗

bioRxiv2018

Bi-clustering interpretation and prediction of correlation between gene expression and protein abundance

Most organisms transcript and protein level only moderately correlate for various reasons, such as regulation of transcription and protein degradation. Better prediction and understanding the correlation between gene expression and protein abundance has been possible by harnessing the matching RNA/protein datasets produced by modern high-throughput RNA-Seq and mass spectrometry methods. In this work, we have utilized some well-studied matching RNA/protein datasets, and explored for the first time a bi-clustering method to cluster genes that have consistent correlation patterns between gene expression and protein abundance. The clustering results have been interpreted from the perspective of both transcriptomic and proteomic features, which show that mRNA half-life, protein half-life and protein structure in concert significantly affect the correlation of gene expression and protein abundance. With these and other carefully selected features, a prediction model based on individual clusters, called Cluster-based Linear prediction Model (CLM), was built and tested on mouse liver mitochondrial, mouse brainstem mitochondrial, Saccharomyces cerevisiae and Danio rerio datasets. CLM could find genes for which protein abundance can be predicted from mRNA data. In summary, based on bi-clustering, feature selection and CLM model, we have established a new and valuable cluster-based protein abundance prediction method.

bioinformatics↗

bioRxiv2017

Reticular adhesions: A new class of adhesion complex that mediates cell-matrix attachment during mitosis

Adhesion to the extracellular matrix (ECM) persists during mitosis in most cell types. Yet, classical adhesion complexes (ACs), such as focal adhesions and focal complexes, do and must disassemble to enable cytoskeletal rearrangements associated with mitotic rounding. Given this paradox, mechanisms of mitotic cell-ECM adhesion remain undefined. Here, we identify reticular adhesions, a new class of AC that is mediated by integrin v{beta}5, formed during interphase and preserved at cell-ECM attachment sites throughout cell division. Consistent with this role, integrin {beta}5 depletion perturbs mitosis and disrupts spatial memory transmission between cell generations. Quantitative imaging reveals reticular adhesions to be both morphologically and dynamically distinct from classic focal adhesions, while mass spectrometry defines their unique composition; lacking virtually all consensus adhesome components. Indeed, remarkably, reticular adhesions are functionally independent of both talin and F-actin, yet are promoted by phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2). Overall, the distinct characteristics of reticular adhesions provide a unique solution to the problem of maintaining cell-ECM attachment during mitotic rounding and division.

cell biology↗

bioRxiv2017

Three-dimensional single cell patterning for mid- to high-throughput studies of tumor cell and extracellular matrix heterogeneity

Cancer heterogeneity includes cancer cell genetic heterogeneity and heterogeneity in the tumor microenvironment (TME)--both stromal cells and extracellular matrix (ECM). Determining which combinations of the vast array of possibly interacting heterogeneities drive tumor progression presents a major multi-disciplinary challenge in cancer research. To make effective treatment decisions this challenge must be addressed. The practical challenge is assessing cellular heterogeneity in a statistically powerful way with respect to targeted TME characteristics. Here we present a simple, but extensible, and low-cost method for conducting mid- to high-throughput and long-term studies of heterogeneous cell responses to various biomechanical stimuli in 3D models mimicking the biomechanical properties of the ECM. Using a platform we term \"the drop-patterning chip\" thousands of cells are simultaneously transferred from microwells and fully embedded, only using the force of gravity, in precise patterns in 3D. This method allows for throughputs approaching flow-through methods, which lack phenotypic information on cell-matrix interactions, and does not rely on expensive or harsh patterning forces, which often times also result in a proximal stiff surface.

bioengineering↗

bioRxiv2017

Rice TSV3 Encoding Obg-like GTPase Protein is Essential for Chloroplast Development during the Early Leaf Stage under Cold Stress

The Spo0B-associated GTP-binding (Obg) proteins occupy a wide variety of roles in the viability of nearly all bacteria. Its detailed roles in higher plants have not yet been elucidated. A novel rice thermo-sensitive virescent mutant tsv3 was identified in this study that displayed albino phenotype at 20{degrees}C before the 3-leaf stage while being normal green at 32{degrees}C or even at 20{degrees}C after the 4-leaf stage. The mutant phenotype was aligned with altered chlorophyll (Chl) content and chloroplast development. Map-based cloning and complementation test showed that TSV3 encoded a kind of small GTP binding protein. Subcellular localization revealed that TSV3 was in chloroplast. TSV3 transcripts were highly expressed in leaves and weak or undetectable in other tissues, suggesting the tissue-specific expression. In tsv3 mutant, the transcriptional levels of certain genes associated with biogenesis of chloroplast ribosomes 50S subunit were severely decreased at the 3-leaf-stage under cold stress, but could be recovered to normal levels at a higher temperature (32{degrees}C). The observations from this study indicated that the rice nuclear-encoded TSV3 plays important roles in chloroplast development at early leaf stage under cold stress.

plant biology↗

bioRxiv2017

Gut microbiota analysis in rats with methamphetamine-induced conditioned place preference

Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analysed through 16S rRNA gene sequencing. The faecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the faecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

microbiology↗