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Biomedical subjects

Jing Zhang

Publications and source records attributed to Jing Zhang.

At least 37 records · Page 2Linked to original sources

Biophysical metabolic modeling of complex bacterial colony morphology.

Microbial colony growth is shaped by the physics of biomass propagation and nutrient diffusion and by the metabolic reactions that organisms activate as a function of the surrounding environment. While microbial colonies have been explored using minimal models of growth and motility, full integration of biomass propagation and metabolism is still lacking. Here, building upon our framework for computation of microbial ecosystems in time and space (COMETS), we combine dynamic flux balance modeling of metabolism with collective biomass propagation and demographic fluctuations to provide nuanced simulations of E. coli colonies. Simulations produced realistic colony morphology, consistent with our experiments. They characterize the transition between smooth and furcated colonies and the decay of genetic diversity. Furthermore, we demonstrate that under certain conditions, biomass can accumulate along "metabolic rings" that are reminiscent of coffee-stain rings but have a completely different origin. Our approach is a key step toward predictive microbial ecosystems modeling. A record of this paper's transparent peer review process is included in the supplemental information.

Models, Biological↗

The TONSL-MMS22L complex and FANCM form an interdependent complex on chromatin to counter replication stress.

FANCM is branchpoint DNA translocase essential for cellular response to replication stress. Here, we show that replication stress stimulates FANCM and the TONSL-MMS22L heterodimer bound to histones H3-H4 to form an interdependent complex on chromatin. TONSL-MMS22L recruits FANCM and Fanconi anemia (FA) core complex to stalled and collapsed forks, maintains FANCM on replication-stressed chromatin, promotes FANCD2 monoubiquitination, facilitates both repair and replication traverse of DNA interstrand crosslinks (ICLs), and suppresses sister chromatid exchanges, through its interactions with FANCM and H3-H4. Reciprocally, both DNA translocase activity and phosphorylation of FANCM facilitate recruitment of TONSL-MMS22L and RAD51 to perturbed forks. Moreover, TONSL-MMS22L and FANCM function together to promote activation of the FA pathway, ICL repair, homologous recombination and replication traverse. Cancer patients with tumors with wildtype FANCM and low expression of TONSL-MMS22L have a more favorable prognosis than those with high expression. Thus, FANCM-TONSL-MMS22L acts coordinately as a complex on chromatin that resolves replication stress, and this complex may present a therapeutic target for wildtype FANCM-linked cancer.

FANCM↗

Genetic and Microbial Analysis of Invasiveness for Escherichia coli Strains Associated With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The adherent-invasive Escherichia coli (AIEC) pathotype is implicated in inflammatory bowel disease (IBD) pathogenesis. AIEC strains are currently defined by phenotypic measurement of their pathogenicity, including invasion of epithelial cells. This broad definition, combined with the genetic diversity of AIEC across patients with IBD, has complicated the identification of virulence determinants. We sought to quantify the invasion phenotype of clinical isolates from patients with IBD and identify the genetic basis for their invasion into epithelial cells. METHODS: A pangenome with core and accessory genes (genotype) was assembled using whole genome sequencing of 168 E coli samples isolated from 13 patients with IBD. A modified assay for invasion of epithelial cells (phenotype) was established with consideration of antibiotic resistance phenotypes. Isolate genotype was correlated to invasiveness phenotype to identify genetic factors that cosegregate with invasion. RESULTS: Pangenome-wide comparisons of E coli clinical isolates identified accessory genes that can cosegregate with invasion phenotype. These correlations found the acquisition of antibiotic resistance genes in clinical isolates compromised the traditional gentamicin protection assays used to quantify invasion. Therefore, an alternate assay, based on amikacin resistance, identified genes cosegregating with invasion. These genes encode an arylsulfatase, a glycoside hydrolase, and genetic islands carrying propanediol utilization and sulfoquinovose metabolism pathways. CONCLUSIONS: This study highlights the importance of incorporating antibiotic resistance screening for invasion assays used in AIEC identification. Accurately screened invasion phenotypes identified accessory genome elements among E coli IBD isolates that correlate with their ability to invade epithelial cells. These results help explain why single genetic markers for the AIEC phylotype are challenging to identify.

Humans↗

Identification of autophagy-related genes as potential biomarkers correlated with immune infiltration in bipolar disorder: a bioinformatics analysis.

BACKGROUND: Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. METHODS: The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. RESULTS: In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. CONCLUSIONS: Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD.

Bipolar Disorder↗

A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.

BACKGROUND: Although there is evidence that ribonucleotide reductase subunit M2 (RRM2) is associated with numerous cancers, pan-cancer analysis has seldom been conducted. This study aimed to explore the potential carcinogenesis of RRM2 in pan-cancer using datasets from The Cancer Genome Atlas (TCGA). METHODS: Data from the UCSC Xena database were analyzed to investigate the differential expression of RRM2 across multiple cancer types. Clinical data such as age, race, sex, tumor stage, and status were acquired to analyze the influence of RRM2 on the clinical characteristics of the patients. The role of RRM2 in the onset and progression of multiple cancers has been examined in terms of genetic changes at the molecular level, including tumor mutational burden (TMB), microsatellite instability (MSI), biological pathway changes, and the immune microenvironment. RESULTS: RRM2 was highly expressed in most cancers, and there was an obvious correlation between RRM2 expression and patient prognosis. RRM2 expression is associated with the infiltration of diverse immune and endothelial cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the cell cycle is involved in the functional mechanisms of RRM2. CONCLUSIONS: Our pan-cancer study provides a comprehensive understanding of the carcinogenesis of RRM2 in various tumors.

Humans↗

Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated alpha-synuclein.

BACKGROUND: The pathogenesis of idiopathic Parkinson's disease (PD) remains elusive, although evidence has suggested that neuroinflammation characterized by activation of resident microglia in the brain may contribute significantly to neurodegeneration in PD. It has been demonstrated that aggregated alpha-synuclein potently activates microglia and causes neurotoxicity. However, the mechanisms by which aggregated alpha-synuclein activates microglia are not understood fully. METHODS: We investigated the role of prostaglandin E2 receptor subtype 2 (EP2) in alpha-synuclein aggregation-induced microglial activation using ex vivo, in vivo and in vitro experimental systems. RESULTS: Results demonstrated that ablation of EP2(EP2-/-) significantly enhanced microglia-mediated ex vivo clearance of alpha-synuclein aggregates (from mesocortex of Lewy body disease patients) while significantly attenuating neurotoxicity and extent of alpha-synuclein aggregation in mice treated with a parkinsonian toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Furthermore, we report that reduced neurotoxicity by EP2-/- microglia could be attributed to suppressed translocation of a critical cytoplasmic subunit (p47-phox) of NADPH oxidase (PHOX) to the membranous compartment after exposure to aggregated alpha-synuclein. CONCLUSION: Thus, it appears that microglial EP2 plays a critical role in alpha-synuclein-mediated neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Improvement in selectivity and storage stability of a choline biosensor fabricated from poly(aniline-co-o-aminophenol).

A choline biosensor was fabricated by using electrochemical doping to immobilize choline oxidase in poly(aniline-co-o-aminophenol) film that exhibits a good electric activity over a wide pH range. Using cyclic voltammetry, impedance measurement and scanning electron microscopy characterized the poly(aniline-co-o-aminophenol) film doped with choline oxidase. The amperometric detection of choline is based on the oxidation of the H2O2 enzymatically produced on the choline biosensor. The choline biosensor has a lower potential dependence. Thus, its operational potential was controlled at a low potential of 0.40 V (vs.SCE). The response current of the choline biosensor increases with increasing temperature from 277.1 to 308.1 K. An apparent activation energy of 30.8 kJ mol(-1) was obtained. The choline biosensor has a wide linear response range from 1x10(-7) to 1x10(-4) M choline with a correlation coefficient of 0.9999 and has a high sensitivity of 127 microA cm(-2), at 0.40 V and pH 8.0. The response time of the biosensor is 15-25 s, depending on the applied potentials. An apparent Michaelis constant and an optimum pH for the immobilized enzyme are 1.8 mM choline and 8.4, respectively, which are very close to those of choline oxidase in solution. The effect of selected organic compounds on the response of the choline biosensor was studied. Together, these findings show that the choline biosensor exhibits a better selectivity to interfering species and a better storage stability.

Alcohol Oxidoreductases↗

A combined dataset of human cerebrospinal fluid proteins identified by multi-dimensional chromatography and tandem mass spectrometry.

Human cerebrospinal fluid (CSF) is an important source for studying protein biomarkers of age-related neurodegenerative diseases. Before characterizing biomarkers unique to each disease, it is necessary to categorize CSF proteins systematically and extensively. However, the enormous complexity, great dynamic range of protein concentrations, and tremendous protein heterogeneity due to post-translational modification of CSF create significant challenges to the existing proteomics technologies for an in-depth, nonbiased profiling of the human CSF proteome. To circumvent these difficulties, in the last few years, we have utilized several different separation methodologies and mass spectrometric platforms that greatly enhanced the identification coverage and the depth of protein profiling of CSF to characterize CSF proteome. In total, 2594 proteins were identified in well-characterized pooled human CSF samples using stringent proteomics criteria. This report summarizes our efforts to comprehensively characterize the human CSF proteome to date.

Cerebrospinal Fluid Proteins↗

Partial scapulectomy for congenital elevation of the scapula.

We treated 26 patients with congenital elevation of the scapula by excising the superomedial part of the scapula. We also simultaneously resected the omovertebral bone when present. A modified inverted L-shape incision was used to release the contracted tissue around the medial edge of the scapula. We evaluated 28 shoulders (26 patients) at a minimum of 10 months followup (mean, 3.9 years; range, 10 months-7 years). The improvement rate for range of shoulder abduction was 59.11%. Eighteen shoulders with preoperative abduction less than 120 degrees achieved an average improvement of 52 degrees, whereas 10 shoulders with a preoperative abduction range greater than 120 degrees achieved an average improvement of 19 degrees. However, there was no difference in the improvement rate of the range of shoulder abduction between the two groups (60.94% versus 56%). Twenty-three shoulders (82.24%) attained various degrees of cosmetic improvement after the operation. There were no neurologic complications during or after surgery. No patients complained of scar problems. Excising the superomedial part of the scapula is a safe, simple operation for treating congenital elevation of the scapula.

Adolescent↗

Effect of aluminum on the nature of the iron species in Fe-SBA-15.

We report the preparation of highly ordered mesoporous Fe-Al-SBA-15 with isolated extraframework Fe species under acidic conditions. The materials were characterized by means of UV resonance Raman spectroscopy, in conjunction with BET, XRD, TEM, UV-vis, H2-TPR, FT-IR, and 27Al MAS NMR spectroscopy. The addition of both Fe and Al to the synthesis gel of SBA-15 results in the formation of isolated extraframework Fe species located close to the framework Al ions and the Fe content an order of magnitude higher than that in Fe-SBA-15 synthesized without Al. The existence of anchored extraframework Fe species was confirmed by the presence of a strong absorption band at 270 nm, hydrogen reduction at relatively low temperature, and the presence of a resonance Raman band at 1140 cm(-1). The location of Fe in close proximity to framework Al nuclei is further supported by 27Al MAS NMR measurements. Two characteristic UV Raman bands at 510 cm(-1) and 1090 cm(-1) excited by 244-nm laser are assigned to Fe-O-Si symmetric and asymmetric stretching modes of isolated tetrahedral Fe ions in the silica framework for Fe-SBA-15. The resonance Raman band at 1140 cm(-1) excited by 325-nm laser is attributed to the asymmetric stretching mode of the isolated extraframework iron species in Fe-Al-SBA-15. The isolated Fe species close to framework Al species are stable in acidic HCl solution, whereas the majority of Fe species in Fe-SBA-15 can be easily removed.

Journal Article↗

Aquaporin 4 regulates the effects of ovarian hormones on monoamine neurotransmission.

Aquaporin 4 (AQP4) is the predominant water channels in the brain of mammals. Our previous study has reported that AQP4 knockout induced sex-specific alterations in neurotransmission, indicating that AQP4 might regulate the interaction between sex hormones and neurotransmission. In the present study, we found that AQP4 knockout decreased the concentrations of estrogen and progestogen. Further study showed that exogenous estrogen decreased DA and 5-HT in cortex, reduced DA and 5-HT in striatum, but increased 5-HT in hippocampus in AQP4+/+ male mice. However, in AQP4-/- male mice, exogenous estrogen almost did not alter the levels of neurotransmitters except for decreasing DA in cortex. In female mice, ovariectomy decreased DA in the striatum of AQP4+/+ mice, but did not alter the levels of DA in AQP4-/- mice. These findings reveal for the first time that AQP4 regulates not only water and ion homeostasis but also the functions of ovarian hormone and neurotransmitter.

Animals↗

Positive association between SIAT8B and schizophrenia in the Chinese Han population.

The Sialyltransferase 8B gene (SIAT8B) is located at 15q26, a susceptibility region for both schizophrenia and bipolar disorder. The protein encoded by this gene has an important role in neural development and sialic acid synthesis on the neural cell adhesion molecule (NCAM). Previous research had indicated that the promoter region of SIAT8B is associated with schizophrenia in the Japanese population. To take this further we carried out an association study based on 643 unrelated schizophrenics and 527 unrelated healthy subjects, all Han Chinese, recruited from Shanghai. Although our results differed from those of the Japanese research, rs3759915, also located in the promoter region of SIAT8B, showed nominally significant association with schizophrenia (P=0.0036). Moreover, haplotypes constructed from rs3759915 and another two SNPs reported in the Japanese study (rs3759914 and rs3759916, also located in promoter region of SIAT8B) which located in the same LD block were significantly associated with schizophrenia (global P=0.0000050). Our findings indicate that SIAT8B may be a candidate susceptibility gene for schizophrenia in the Chinese Han population and may also provide further support for the potential importance of polysaccharide-synthesizing genes in the etiology of schizophrenia.

Adult↗

Helper virus-independent trans-replication of hepatitis C virus-derived minigenome.

We have previously described a synthetic T7-driven cDNA minigenome containing the antisense sequence of luciferase gene and internal ribosome entry site of encephalomyocarditis virus flanked by 5'- and 3'-end sequences of hepatitis C virus (HCV) that contain cis-acting replication elements. Synthesis of minus-strand RNA from the artificial minigenome was determined by using Huh-7 cells harboring autonomously replicating HCV subgenome as a helper for provision of functional replication components. To further confirm and extend these studies, we investigated here whether the minigenome replication system could be reconstituted by transfection of naïve Huh-7 cells with plasmid expressing nonstructural (NS) proteins. Reporter assay and Northern blot analysis revealed that trans-expression of NS proteins from 3 to 5 resulted in high level of luciferase activity and synthesized minus-strand RNA. The analogous result was also obtained with the minigenome derived from HCV 2a, and both HCV 1b- and 2a-derived NS protein were able to support the chimeric minigenomes whose 5'- or 3'-end was replaced by the respective region of the heterologous virus. These results provide a basis for establishing the reverse genetic system that is helpful to study cis- and trans-acting factors involved in HCV RNA replication.

Cell Line, Tumor↗

Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia.

The chitinase 3-like 1 gene (CHI3L1) is abnormally expressed in the hippocampus of subjects with schizophrenia and may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia. Here, we provide evidence that the functional variants at the CHI3L1 locus influence the genetic risk of schizophrenia. First, using case-control and transmission/disequilibrium-test (TDT) methodologies, we detected a significant association between schizophrenia and haplotypes within the promoter region of CHI3L1 in two independent cohorts of Chinese individuals. Second, the at-risk CCC haplotype (P=.00058 and .0018 in case-control and TDT studies, respectively) revealed lower transcriptional activity (P=2.2 x 10(-7)) and was associated with lower expression (P=3.1 x 10(-5)) compared with neutral and protective haplotypes. Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype. In contrast, the protective TTG haplotype was associated with a high level of CHI3L1 expression. Our findings identify CHI3L1 as a potential schizophrenia-susceptibility gene and suggest that the genes involved in the biological response to adverse environmental conditions are likely to play roles in the predisposition to schizophrenia.

Adipokines↗

Electron-rich, bulky PNN-type ruthenium complexes: synthesis, characterization and catalysis of alcohol dehydrogenation.

Reaction of the electron-rich, bulky tridentate PNN ligand (PNN=2-di-tert-butylphosphinomethyl-6-diethylaminomethylpyridine) with Ru(PPh3)3Cl2 at 65 degrees C resulted in formation of the mononuclear dinitrogen complex (PNN)Ru(Cl)2N2 (minor) and the N2 bridged Ru(II) dinuclear complex [(PNN)Ru(Cl)2]2(micro-N2) (major). These complexes can be interconverted; passing argon through a solution of the mixture resulted in formation of pure . The cationic square-pyramidal [(PNN)Ru(PPh3)Cl]OTf was obtained by the reaction of complex with silver triflate followed by PPh3. Reaction of complex with CO yielded (PNN)Ru(CO)Cl2, which upon reaction with one equiv. of AgBF4 gave the cationic [(PNN)Ru(CO)Cl]BF4. The dicationic [(PNN)Ru(CO)(H2O)(acetone)](BF4)2 was obtained from with 2 equiv. of AgBF4 in acetone solution. Complexes , and were structurally characterized by X-ray crystallography. Complexes and upon addition of an equivalent of base, catalyzed the dehydrogenation of secondary alcohols to the corresponding ketones and primary alcohols to esters in good yields and high selectivity accompanied with the evolution of hydrogen gas.

Journal Article↗

The physical and functional interaction of NDRG2 with MSP58 in cells.

NDRG2, a member of N-Myc downstream regulated gene family, exerts the important functions in cell differentiation and tumor suppression. Although the ectopic expressed Ndrg2 inhibits the proliferation of tumor cells, its intracellular signal transduction pathway is hardly known. Here, we identified MSP58, a 58-kDa microspherule protein, as an interacting partner of human Ndrg2 by using yeast two-hybrid screening. The interaction was confirmed by glutathione S-transferase pull-down assay in vitro and by co-immune-precipitation assay in vivo. The forkhead associated domain of MSP58 is essential for its interaction with Ndrg2. Ndrg2 could co-localize with MSP58 in nuclear of HeLa cell during cell stress. Furthermore, the modulation of Ndrg2 level influences the cell cycle process together with MSP58. In conclusion, the findings offered a novel insight into the physiological roles of Ndrg2.

Animals↗

Introduction of G1 phase arrest in Human Hepatocellular carcinoma cells (HHCC) by APMCF1 gene transfection through the down-regulation of TIMP3 and up-regulation of the CDK inhibitors p21.

We previously found that there was up-regulation of APMCF1 expression in apoptotic MCF-7 cells. Moreover, bioinformatics analysis has found that APMCF1 molecules had similar size and structure with molecules which belong to small G-protein superfamily. We presume that APMCF1 plays certain biological role in the regulation of cell proliferation and apoptosis. In this study, we first detected the expression pattern of APMCF1 in human hepatocellular carcinoma cell line and find no expression in Human Hepatocellular carcinoma cells (HHCC) and enhanced expression in HepG2 cells. Expression of liposome-mediated ectogenic APMCF1 induced inhibition of HHCC growth and cell cycle, and RNAi inhibited APMCF1 expression and promoted HepG2 cell growth. Results of cell cycle gene chips analysis showed up-regulation of p21 expression and down-regulation of TIMP3 in HHCC cells expressing ectogenic APMCF1, indicating that APMCF1 participates at least partially in cell cycle regulation through regulating genes such as p21 and TIMP3.

Carcinoma, Hepatocellular↗