Application of neural network autoencoder algorithm in the cancer informatics research / 生物工程学报

Cancers have been widely recognized as highly heterogeneous diseases, and early diagnosis and prognosis of cancer types have become the focus of cancer research. In the era of big data, efficient mining of massive biomedical data has become a grand challenge for bioinformatics research. As a typical neural network model, the autoencoder is able to efficiently learn the features of input data by unsupervised training method and further help integrate and mine the biological data. In this article, the primary structure and workflow of the autoencoder model are introduced, followed by summarizing the advances of the autoencoder model in cancer informatics using various types of biomedical data. Finally, the challenges and perspectives of the autoencoder model are discussed.

Mouse liver proteome database / 生物工程学报

The liver is the metabolic center of mammalian body. Systematic study on liver's proteome expression under different physiological and pathological conditions helps us understand the functional mechanisms of the liver. With the rapid development of liquid chromatography tandem mass spectrometry technique, numerous studies on liver physiology and pathology features produced a large number of proteomics data. In this paper, 834 proteomics experiments of mouse liver were systematically collected and the mouse liver proteome database (Mouse Liver Portal, http://mouseliver.com) was established. The Mouse Liver Portal contains the liver's proteomics data under different physiology and pathology conditions, such as different gender, age, circadian rhythm, cell type and different phase of partial hepatectomy, non-alcoholic fatty liver. This portal provides the changes in proteins' expression in different conditions of the liver, differently expressed proteins and the biological processes which they are involved in, potential signal transduction and regulatory networks. As the most comprehensive mouse liver proteome database, it can provide important resources and clues for liver biology research.

Construction of human breast cancer tumor transplantation model in nude mice and isolation of tumor infiltrating myeloid cells / 军事医学

Objective To establish neoplasm transplantation models of breast cancer cells in BALB /c nude mice and to isolate tumor infiltrating myeloid cells.Methods pHAGE-EF-ZsG-DEST plasmid,pMD2.G plasmid and psPAX2 were transfected into BT474 using the method of calcium phosphate transfection .The positive cells were selected by flow cytometry and implanted in the fat pad of nude mice .A tumor model of breast cancer cells implanted in nude mice was constructed, and the tumor infiltrating myeloid cells were isolated .Conclusion Tumor infiltrating myeloid cells are successfully isolated, which will contribute to the study of the functions of tumor infiltrating myeloid cells .

Mouse liver phosphoproteome methodology optimization and kinase analysis / 军事医学

Objective To analyze the construction of mouse liver phosphoproteome and phosphorylated kinases to provide useful information for integrating mouse kinase phosphorylation regulatory networks.Methods A new method was established to identify phosphoproteome from the mouse liver.First of all, liver protein was digested with trypsin before the resulting peptides were subjected to a two-step phosphopeptide enrichment and separation procedure consisting of TiO2 chro-maphy enrichment combined with high pHHPLC separation.Samples were injected onto aNanolC-Ultra-2Dplus system cou-pled to an AB-Sciex 5600 Triple TOF mass spectrometer instrument.Then data analysis was performed to provide information of new identified phosphorylation sites of kinase.Results and Conclusion Using our efficient and high-throughput platform, we reported the identification of 5386 phosophorylation sites and 4553 phosphopeptides from 1533 proteins of the mouse liver.126 new phosphorylation sites were identified from 116 kinases, which provides valuable infor-mation for phosphorylation networks in the mouse liver.

Role of hepatic macrophages in acute liver injury / 军事医学

Objective To elaborate the role of hepatic inherent macrophages and monocyte-derived macrophages in acute liver injury.Methods A model of acute liver injury in mice was induced via intraperitoneally injection of CCl 4 .Af-ter CCl4 injection, analysis of the expression of CD45, F4/80, Ly6C and CD11b on the hepatic macrophage surface was performed by flow cytometry at 24, 48 and 72 h before the hepatic inherent macrophages (CD45+F4/80hi) and monocyte-de-rived macrophages ( CD45+F4/80 lo ) were sorted at the same time .The relative expression of cytokines in the two popula-tions of macrophages was detected by qRT-PCR.Results Compared with control , the number of total F4/80 +cells in the liver was markedly increased after CCl 4 injection, especially at 72 h.The number of CD45+F4/80lo cells increased signifi-cantly after CCl4 injection 24 h.The mRNA levels of MCP-1, TNF-α, TGF-β1, matrix metalloproteinase(MMP)-12 and MMP-13 were elevated significantly both in F 4/80 hi and F4/80 lo macrophages .IL-12βand IL-6 mRNA levels increased significantly only in F4/80hi macrophages, while the level of MMP-9 mRNA increased markedly only in F4/80lo macropha-ges.When compared with F4/80lo macrophages, MCP-1 and MMP-12 mRNA levels were elevated significantly , while the level of TNF-αmRNA decreased significantly in F4/80hi macrophages.Conclusion In acute liver injury, hepatic inherent macrophages and monocyte-derived macrophages both express inflammatory cytokines , promoting inflammation response and leading to liver damage .The ability to recruit inflammatory monocytes into the liver is much stronger ,the expression of in-flammatory cytokines ( IL-12βand IL-6 ) and MMP-12 is higher , but the expression of inflammatory cytokines ( TNF-α) MMP-9 is lower in hepatic inherent macrophages than in monocyte-derived macrophages .

Nusap1 is essential for neural crest cell migration in zebrafish

Microtubules play important roles in mitotic spindle assembly and chromosome segregation to maintain normal cell cycle progression. A number of microtubule-associated proteins have been identified in epithelial and neural cell cultures; however, their physiological significance is not well characterized due to the lack of appropriate in vivo animal models. Nucleolar spindle-associated protein (NuSAP) is a microtubule-binding protein and is reported to be involved in mitosis by cell culture studies. In this report, we identified the zebrafish homologue of human NuSAP and investigated its expression profile and functions. Using in situ hybridization, we demonstrated that transcripts of zebrafish nusap1 are specifically expressed in the retina, forebrain, hindbrain and neural crest. When the in vivo expression of nusap1 was knocked down through antisense oligonucleotide morpholino technology, the morphants of nusap1 showed impaired morphogenesis in the trunk and yolk extension, implying the involvement of Nusap1 in cell migration. Mechanistic studies revealed that nusap1 morphants have an altered expression pattern of neural crest markers crestin and sox9b, but normal expression of blood vessel and notochord markers gata1 and shh. In addition, nusap1 mRNA injection caused serious apoptosis in retina and hindbrain tissue, and these phenotypes can be rescued by co-injection of morpholino against nusap1. These observations not only suggest a role for Nusap1 in connecting apoptosis with cell migration, but also provide strong evidences that Nusap1 is potentially involved in morphogenesis in vertebrates.

Status and Development Trend on Tumor Metastasis / 生物化学与生物物理进展

Tumor metastasis, the main characteristic of malignance tumor, is the primary cause of death for most cancer patients.The initiation of tumor metastasis involves complex signaling pathway within tumor cell and microenvironment, mediating primary tumor metastasis, invasion, survival and arrest in the blood circulation, and progressive growth at the distant site.The most research on the mechanism of tumor metastais will help understand the metastasis process, and identify promising molecular targets for cancer clinical diagnosis and treatment.

Progress in Function and Regulation of Protein Neddylation / 生物化学与生物物理进展

NEDD8 is a member of the ubiquitin-like proteins. The overall structure of NEDD8 is quite similar to ubiquitin. Covalent conjugation of NEDD8 to proteins at the post-translational level is called Neddylation. Neddylation occurs similarly to ubiquitination and need enzyme cascades involving E1, E2 and E3. Neddylation has been demonstrated to be essential to maintain the ubiquitin ligase activity of Cullin-Roc based E3 ligases. Compared with the ubiquitination which was widely studied in the past two decades, few substrates were identified for Neddylation and the physiological functions of Neddylation need further investigations. The current progress of function and regulation of protein Neddylation will be reviewed.

In situ Fabrication and Application of Protein Microarray With Cell-free System / 生物化学与生物物理进展

Protein is one of major bio-functional performers. As one of several crucial proteomic research approaches, protein microarray has these following advantages: high-throughput, high sensitivity, quick detection and so on. Meanwhile, there are some critical factors that are important to the further development of protein microarray technology, for example, how to express and purify proteins for the research of protein microarray, how to immobilize proteins onto the substrate and keep the bio-function of proteins immobilized. Nano-biotechnology and cell-free expression system have been used to fabricate protein microarray by the way of immobilizing target genes onto the substrate and directly expressing corresponding proteins, which provides a new strategy to fabricate more complicated microarray. The stragegy and its progress were summarized———fabrication of protein microarray based on DNA, including immobilization of target genes, cell-free expression to proteins, immobilization of renascence proteins, advantages and drawbacks of the methods of protein chip fabrication etc.

Progress in The Study of Novel Tumor Suppressor of ING Family / 生物化学与生物物理进展

Inhibitor of growth (ING) family proteins belong to candidate tumor suppressor proteins. The ING proteins participate in PtdInsPs-mediated lipid signaling and hormone signaling pathways. They are associated with histone acetyltransferase, histone deacetylase and play a role in chromatin remodeling and gene transcription regulation. ING proteins regulate cell growth, apoptosis and DNA damage repair in p53 dependent manner; thus linking the processes of cell cycle regulation, apoptosis and cellular aging through epigenetic regulation of gene expression.

mRNA Display Technology / 生物化学与生物物理进展

mRNA display provides a new powerful tool for in vitro selecting of peptides and proteins.In the selecting process,peptides are covalently attached to their own mRNA to form mRNA-protein fusions.These mRNA-protein fusions enable in vitro selection of peptide and protein libraries of more than 1013 different sequences.The experiment conditions and protocols have been optimized in recent years.The application of mRNA display technology is mainly in the discovery of ligands for many kinds of target molecules and the analysis and mechanism elucidation on interaction between proteins.With its great potential,there will be a wide application foreground in the application of mRNA display.

Role for The Bcl-2 Family Proteins and BH3 Domain in Apoptosis / 生物化学与生物物理进展

Apoptosis action is primarily exerted at the level of mitochondira, in which Bcl-2 family of proteins play an important role in its regulation. Bcl-2 family consists of anti-apoptotic and pro-apoptotic members. The anti-apoptotic members usually exist in the outer mitochondrial membrane and inhibit cell death via interaction with pro-apoptotic counterparts BH3 domain. Pro-apoptotic members are commonly localize in the cytoplasm. A series of events occured, such as typical Bax conformational change, BAD and Bik phosphorylation as well as Bid and Bim proteolysis in response to several death stimuli. As a result, these pro-apoptotic proteins directly integrate to the outer mitochondrial membranes. Finally, mitochondrial permeability transition pore is opened, by followed the release of apoptogenic factors from the mitochondrial intermembrane space, including cytochrome c, apoptosis inducing factor(AIF) and Smac, then the activation of downstream caspases and execution of cell death.

An Integrated Strategy for Functional Analysis in Large-scale Proteomic Research by Gene Ontology / 生物化学与生物物理进展

Data analysis poses a significant challenge to the large-scale proteomics studies. Based on the structured and controlled vocabularies-Gene Ontology (GO), and the GO annotation from related databases, a strategy composed of several programs and local databases is developed to identify the functional distribution and the significantly enriched functional categories of the proteomic expression profile. It would be helpful for understanding the overall functions of these identified proteins and supply the fundamental information for further bioinformatics exploration. This strategy has been successfully used in the Human Fetal Liver (HFL) proteomic research, which is available online at http://www.hupo.org.cn/GOfact/.

Advances in the study of SR protein family / 基因组蛋白质组与生物信息学报·英文版

The name of SR proteins is derived from their typical RS domain that is rich in serine (Ser, S) and arginine (Arg, R). They are conserved in evolution. Up to now, 10 members of the SR protein family have been identified in humans. SR proteins contain one or two RNA binding motifs aside from the RS domain, and also possess special biochemical and immunological features. As to the functions of SR proteins, they facilitate the recruitment of the components of splicesome via protein-protein interaction to prompt the assembly of early splicesome; while in alternative splicing, tissue-specifically expressed SR protein along with the relative ratio of SR protein and heterogeneous nuclear ribonucleoprotein (hnRNP) is composed of two main regulative mechanisms to alternative splicing. Almost all of the biochemical functions are regulated by reversible phosphorylation.

Construction and Application of a Large-scale DNA Sequence Analysis System Based on PC/Linux / 生物化学与生物物理进展

More and more DNA sequences have been obtained since the start-up of human genome project. Powerful system is badly needed for data mining on these DNA sequences. Based on a personal computer and Linux operating system, the Phred/Phrap/Consed software and Blast software were used to construct a platform for batch analysis of the sequences, including identifying raw DNA sequence from chromatogram file, vector sequence removing, contig analysis (sequence assembly), repeat sequence identifying and sequence similarity analysis. Result demonstrated that this robust platform could accelerate data analysis for large-scale DNA sequencing.

The reversal effects of recombinant human augmenter of liver regeneration to immunocomplex induced liver fibrosis / 中国病理生理杂志

To observe the anti-fibrosis activity of recombinant human augmenter of liver regeneration (hALR). METHODS: Albumin induced rat model of liver fibrosis was established and hALR was given peritoneally after the model production. Serum concentration of alanine aminotransferase(ALT), aspartic aminotransferase(AST), lactate dehydrogenase(LDH), hepatic collagen contents and pathological examination were selected as observing parameter. RESULTS: Recombinant human augmenter of liver regeneration (hALR) could decrease ALT, AST, LDH concentration of fibrotic rats. The measurements of hepatic collagen contents showed that hepatic collagen contents in hALR treatment group was much lower than those of model group and negative control group. Pathological examination also indicated that the degree of liver fibrosis in hALR treatment group was attenuated in comparison with those of model group and negative control group. CONCLUSION: Recombinant human augmenter of liver regeneration (hALR) had reversal effects on immunocomplex induced rat liver fibrosis.