Institutes of Biomedical science

Shanghai, China

Institutes of Biomedical science

Shanghai, China
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Zhou X.,Institutes of Biomedical science | Yang P.,Institutes of Biomedical science | Jiang Y.,Tsinghua UniversityShenzhen518055 Peoples Republic of China
Journal of Polymer Science, Part A: Polymer Chemistry | Year: 2017

Molecular weights of seven poly(phenylene ethynylene)-based water-soluble conjugated polyelectrolytes (CPEs) obtained through Sonogashira coupling are determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A standard sample preparation protocol is developed to characterize the seven CPEs using 2,5-dihydroxybenzoic acid as the matrix (M) and AgTFA as the cationization reagent (CR). High-quality MALDI mass spectra are obtained at volume mixing ratios (CPE/M/CR) of 5/5/1 for anionic polymers (P1-P4) and 5/50/1 for cationic polymers (P5-P7). Molecular weight, molecular weight distribution, and end-group information are analyzed. The effects of molecular weight of CPEs on optical and quenching properties are also studied. © 2017 Wiley Periodicals, Inc.

Gu X.,Fudan University | Guo L.,Fudan University | Ji H.,Fudan University | Sun S.,Fudan University | And 5 more authors.
Clinical Genetics | Year: 2015

The genetic heterogeneity of non-syndromic hearing loss (NSHL) has hampered the identification of its pathogenic mutations. Several recent studies applied targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to simultaneously screen a large set of known hearing loss (HL) genes. However, most of these studies were focused on familial cases. To evaluate the effectiveness of TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated sporadic NSHL probands, who had various levels of HL and were excluded for mutations in GJB2, MT-RNR1, and SLC26A4 genes. TGE and MPS were performed on 131 known HL genes using the Human Deafness Panel oto-DA3 (Otogenetics Corporation., Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate = 12.7%). Among these variants, 10 were novel compound heterozygous mutations. The identification of pathogenic mutations could predict the progression of HL, and guide diagnosis and treatment of the disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Xu Y.,Institutes of Biomedical science | Xu Y.,Fudan University | Li F.,Institutes of Biomedical science | Li F.,Fudan University | And 14 more authors.
Cancer Research | Year: 2014

Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth. Cancer Res; 74(13); 3630-42. © 2014 American Association for Cancer Research.

Jin Y.,Fudan University | Yang H.,Fudan University | Wei Z.,Fudan University | Ma H.,Fudan University | And 3 more authors.
Molecular Plant | Year: 2013

Drought affects rice reproduction and results in severe yield loss. The developmental defects and changes of gene regulation network in reproductive tissues under drought stress are largely unknown. In this study, rice plants subjected to reproductive stage drought stress were examined for floral development and transcriptomic changes. The results showed that male fertility was dramatically affected, with differing pollen viability in flowers of the same panicle due to aberrant anther development under water stress. Examination of local starch distribution revealed that starch accumulated abnormally in terms of position and abundance in anthers of water-stressed plants. Microarray analysis using florets of different sizes identified >1000 drought-responsive genes, most of which were specifically regulated in only one or two particular sizes of florets, suggesting developmental stage-dependent responses to drought. Genes known to be involved in tapetum and/or microspore development, cell wall formation or expansion, and starch synthesis were found more frequently among the genes affected by drought than genome average, while meiosis and MADS-box genes were less frequently affected. In addition, pathways related to gibberellin acid signaling and abscisic acid catabolism were reprogrammed by drought. Our results strongly suggest interactions between reproductive development, phytohormone signaling, and carbohydrate metabolism in water-stressed plants.

Yang H.,Fudan University | Lu P.,Pennsylvania State University | Wang Y.,Fudan University | Ma H.,Fudan University | Ma H.,Institutes of Biomedical science
Plant Journal | Year: 2011

Meiosis is essential for eukaryotic sexual reproduction, with two consecutive rounds of nuclear divisions, allowing production of haploid gametes. Information regarding the meiotic transcriptome should provide valuable clues about global expression patterns and detailed gene activities. Here we used RNA sequencing to explore the transcriptome of a single plant cell type, the Arabidopsis male meiocyte, detecting the expression of approximately 20 000 genes. Transcription of introns of >400 genes was observed, suggesting previously unannotated exons. More than 800 genes may be preferentially expressed in meiocytes, including known meiotic genes. Of the 3378 Pfam gene families in the Arabidopsis genome, 3265 matched meiocyte-expressed genes, and 18 gene families were over-represented in male meiocytes, including transcription factor and other regulatory gene families. Expression was detected for many genes thought to encode meiosis-related proteins, including MutS homologs (MSHs), kinesins and ATPases. We identified more than 1000 orthologous gene clusters that are also expressed in meiotic cells of mouse and fission yeast, including 503 single-copy genes across the three organisms, with a greater number of gene clusters shared between Arabidopsis and mouse than either share with yeast. Interestingly, approximately 5% transposable element genes were apparently transcribed in male meiocytes, with a positive correlation to the transcription of neighboring genes. In summary, our RNA-Seq transcriptome data provide an overview of gene expression in male meiocytes and invaluable information for future functional studies. © 2011 Blackwell Publishing Ltd.

Guo C.,Fudan University | Ge X.,Fudan University | Ma H.,Fudan University | Ma H.,Institutes of Biomedical science
Plant Molecular Biology | Year: 2013

Drought is one of the critical factors limiting reproductive yields of rice and other crops globally. However, little is known about the molecular mechanism underlying reproductive development under drought stress in rice. To explore the potential gene function for improving rice reproductive development under drought, a drought induced gene, Oryza sativa Drought-Induced LTP (OsDIL) encoding a lipid transfer protein, was identified from our microarray data and selected for further study. OsDIL was primarily expressed in the anther and mainly responsive to abiotic stresses, including drought, cold, NaCl, and stress-related plant hormone abscisic acid (ABA). Compared with wild type, the OsDIL-overexpressing transgenic rice plants were more tolerant to drought stress during vegetative development and showed less severe tapetal defects and fewer defective anther sacs when treated with drought at the reproductive stage. The expression levels of the drought-responsive genes RD22, SODA1, bZIP46 and POD, as well as the ABA synthetic gene ZEP1 were up-regulated in the OsDIL-overexpression lines but the ABA degradation gene ABAOX3 was down-regulated. Moreover, overexpression of OsDIL lessened the down-regulation by drought of anther developmental genes (OsC4, CYP704B2 and OsCP1), providing a mechanism supporting pollen fertility under drought. Overexpression of OsDIL significantly enhanced drought resistance in transgenic rice during reproductive development, while showing no phenotypic changes or yield penalty under normal conditions. Therefore, OsDIL is an excellent candidate gene for genetic improvement of crop yield in adaption to unfavorable environments. © 2013 Springer Science+Business Media Dordrecht.

Ge X.,Fudan University | Chang F.,Fudan University | Ma H.,Fudan University | Ma H.,Institutes of Biomedical science | Ma H.,Pennsylvania State University
Current Biology | Year: 2010

Plant reproductive development is a complex process with diploid and haploid phases, including male and female organogenesis, meiosis, gametogenesis, pollination and fertilization. A number of regulatory mechanisms control both diploid and haploid cell division and differentiation, especially cell-cell signaling pathways mediated by receptor-linked protein kinases with prominent roles in early male development, and hormonal signaling pathways crucial for later events in male and female reproductive development. Furthermore, transcriptional networks control the proper formation of specific cell layers and embryo sac cell specification. © 2010 Elsevier Ltd.

Qi D.,Institutes of Biomedical science | Zhang H.,Institutes of Biomedical science | Tang J.,Institutes of Biomedical science | Deng C.,Institutes of Biomedical science | Zhang X.,Institutes of Biomedical science
Journal of Physical Chemistry C | Year: 2010

In this work, we reported an alternative strategy to the synthesis of core-shell structure Fe3O4@C@Au magnetic microspheres by a self-assembly approach. The as-synthesized Fe3O4@C@Au magnetic microspheres were functionalized with 4-mercaptophenylboronic acid and successfully applied for selective enrichment of glycopeptides and glycoproteins. At first, the Fe3O4@C magnetic microspheres were synthesized by two-step reactions including solvothermal and hydrothermal reactions. Then, Fe3O4@C@Au magnetic microspheres with core-shell structure were obtained by a self-assembly approach. Finally, the Fe3O4@C@Au magnetic microspheres were modified with 4-mercaptophenylboronic acid. The 4-mercaptophenylboronic acid-modified Fe 3O4@C@Au magnetic microspheres were successfully applied to selective enrichment of glycoproteins and glycopeptides. © 2010 American Chemical Society.

Yang H.,Institutes of Biomedical science | Xiong Y.,Institutes of Biomedical science | Guan K.L.,Institutes of Biomedical science
Science China Life Sciences | Year: 2013

Altered metabolism in cancer was first discovered by Otto Warburg early last century. Although the Warburg Effect has been widely used in tumor detection, relatively little progress had been made in mechanistic understanding of cancer metabolism in the subsequent eight decades. Genetic studies have recently identified mutations in human cancer targeting multiple enzymes involved in intermediate metabolism. One emerging mechanism common to these mutant enzymes is the accumulation of a metabolite that alters the epigenetic control. © 2013 The Author(s).

Wan Y.M.,Institutes of Biomedical science
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012

To construct and compare the immunogenicities of DNA vaccines expressing pol genes derived from B`/C and A/E recombinant subtypes of HIV-1 in China. Two DNA vaccines were constructed by inserting the codon optimized pol genes derived from B'/C and A/E subtypes of HIV-1 into mammalian expression vector pSV1.0. In vitro expression efficiencies of the two DNA vaccines were determined by Western blotting and their immunogenicities were compared by i.m. immunizing female BALB/c mice. After immunization, mice splenocytes were isolated sterilely and IFN-γ based enzyme linked immunospot assay (ELISPOT) was employed to read out the specific T cell immunity. The constructed DNA vaccines were validated by restriction enzyme digestion and DNA sequencing. Western blotting result showed both of the two DNA vaccines could be expressed at appreciable levels in vitro. Under the stimulation of Consensus B Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (636±178) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (468±265)SFCs/10(6) splenocytes (P=0.412). Under the stimulation of HIV-1 AE2f Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (1378±611) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (713±61) SFCs/10(6) splenocytes (P=0.134). Further analysis suggested pSVAE-Pol induced specific T cell responses mainly focused on Pol 1 peptide pool, while, in addition to induce Pol 1 specific T cell responses, pSVCN-Pol could also elicit T cell responses against consensus B Pol 2 peptide pool. Although pSVAE-Pol was more immunogenic, pSVCN-Pol could induce T cell responses against broader epitope spectrum. Rational vaccine design may need combine them together.

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