Lipidomics: Potential role in risk prediction and therapeutic monitoring for diabetes and cardiovascular disease

Lipidomics has developed rapidly over the past decade to the point where clinical application may soon be possible. Developments including high throughput technologies enable the simultaneous quantification of several hundred lipid species, thereby providing a global assessment of lipid metabolism. Given the key role of lipids in the pathophysiology of diabetes and cardiovascular disease, lipidomics has the potential to:

i)

Significantly improve prediction of future disease risk,     

What the semantic web could do for the life sciences

Scientific research is predicated on the effective exchange of knowledge. The effective exchange of data and accompanying interpretation underpin new hypotheses and experimental designs, typically followed by a community-based process of debate and rebuttal. This community-driven process clarifies and strengthens the elements of facts and hypothesis. Within the life sciences, the result of this process is a collective understanding of emerging biological viewpoints. The methodologies for community debate and knowledge transfer have changed little over the past twenty years, although both scientific instrumentation and publishing technologies have undergone revolutionary change. It is proposed that newly published recommendations from the World Wide Web Consortium (W3C), which handle the domain and process-specific semantics of life sciences, would better support the application of peer-reviewed knowledge in discovery research. W3C semantic web technologies support flexible, extensible and evolvable knowledge transfer and reuse, enabling scientists and their organizations to increase efficiency across the scientific process.     

In silico prediction and ex vivo evaluation of potential T-cell epitopes in glycoproteins 4 and 5 and nucleocapsid protein of genotype-I (European) of porcine reproductive and respiratory syndrome virus

T-cell epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) glycoproteins 4 (GP4), 5 (GP5) and nucleocapsid (N) were predicted using bioinformatics and later tested by IFN-γ ELISPOT in pigs immunized with either a modified live vaccine (MLV) or DNA (open reading frames 4, 5 or 7). For MLV-vaccinated pigs, immunodominant epitopes were found in N but T-epitopes were also found in GP4 and GP5. For DNA-immunized pigs, some peptides were differently recognized. Using a large set of PRRSV sequences it was shown that N contains a conserved epitope and that for GP5, the genotype-I counterparts of previously reported epitopes of genotype-II strains were also immunogenic.     

Use of genomics to select antibacterial targets

The problem of antibiotic resistance has eroded the usefulness of our arsenal of effective antibiotics. There is a need for new strategies to discover and develop new, effective drugs. The advent of the microbial genomics era has provided a wealth of information on a variety of microorganisms. This has allowed the identification and/or validation of a number of gene products that could serve as targets for the discovery of novel antibacterial agents. New genetic techniques and approaches have arisen in an attempt to exploit this newly available genomic data. Both random and targeted gene disruption efforts have proven effective in this process. Many of these methods would have been difficult to accomplish without DNA sequence and bioinformatics analyses. Several targets have been selected to further characterize and screen for inhibitors and one has yielded two clinical candidates.     

肝癌肝移植术后肿瘤复发相关蛋白的鉴定及生物信息学分析

目的 鉴定肝癌肝移植术后肿瘤复发相关蛋白并进行相关生物信息学分析.方法 取肝癌肝移植术后3年患者原发瘤标本,根据肿瘤复发情况,分为复发组(10例)和未复发组(10例).用双向电泳对两组总蛋白进行分离,质谱鉴定差异蛋白;用Gene Ontology和MetaCore软件进行生物信息学分析;用蛋白印迹法测定核纤层蛋白A/C(lamin A/C)的表达.结果 共鉴定出37个差异蛋白,相对于未复发组,复发组中表达上调2倍以上的蛋白16个,表达下调2倍以上的蛋白21个.按Gene Ontology进行分类发现它们主要分布于细胞浆(27％)和细胞器(24％);主要参与体内催化反应(38％)和结合反应(24％)等生物学功能.MetaCore数据库分析,发现多种蛋白参与细胞凋亡、细胞死亡、细胞发育过程的信号调控网络.我们应用蛋白免疫印迹对lamin A/C在两组间的差异表达情况进行了再验证,验证结果与质谱结果吻合.结论 肝癌肝移植术后转移复发与多种蛋白表达改变相关,lamin A/C可能为移植后肿瘤转移复发的潜在分子靶点.     

紧密连接蛋白Claudin-15基因5′调控区序列的生物信息学分析

目的:研究紧密连接蛋白Claudin-15基因转录调控机制,并对潜在的转录因子结合位点进行分析。方法:利用BLAST比对获得Claudin-15基因5′调控区序列;利用模序识别分析TATA-box、GC-box和CAAT-box;利用在线分析软件Neural Network Promoter Prediction和PROMOTER 2.0分析Claudin-15基因5′调控区序列中启动子;利用在线分析软件EMBOSS和CpG Island Searcher分析Claudin-15基因5′调控区序列中CpG岛位置;利用在线分析软件TFSEARCH分析Claudin-15基因5′调控区序列中潜在的转录因子结合位点。结果:Claudin-15基因5′调控区序列中存在1个CAAT-box和1个GC-box,没有TATA-box;Caudin-15基因可能存在4个启动子位点;CpG岛为70bp区间(51～120bp)、77bp区间(312～388bp)、72bp区间(2 029～2 100bp)、204bp区间(1 745～1 948bp);结果显示评分在85分以上(Score Threshold:85.0)时,该区域具有470个潜在的转录因子结合位点;评分在90分以上(Score Threshold:90.0)时,该区域具有162个潜在的转录因子结合位点;评分在95分以上(Score Threshold:95.0)时,该区域具有59个潜在的转录因子结合位点;评分在100分(ScoreThreshold:99.0)时,该区域具有14个潜在的转录因子结合位点。结论:通过生物信息学的方法对于Claudin-15基因转录起始位点、启动子区域和潜在的转录因子结合位点进行预测,对于科研具有十分重要的指导意义。     

Discontinuous epitopes on the C2 domain of coagulation Factor VIII mapped by computer-designed synthetic peptides

The occurrence of alloantibodies against Factor VIII (FVIII) is the main iatrogenic complication in haemophilia A (HA). Anti-FVIII autoantibodies may also spontaneously appear in non-HA patients, leading to acquired haemophilia A. In both contexts, the antibody response against FVIII is complex and difficult to analyse due to the lack of suitable tools. Our purpose was to comprehensively map, at the amino acid level, discontinuous epitopes of the C2 domain of FVIII targeted by patients' antibodies. We synthesized 33 synthetic peptides, which were predicted by the bioinformatic algorithm PEPOP to mimic C2 domain discontinuous epitopes. Using an inhibition assay based on the x-MAP technology, we evaluated their ability to block the binding to the C2 domain of anti-C2 domain antibodies from pooled plasma samples. Nine peptides were thus selected and tested again in individual plasma samples. Our results support the view that C2 domain epitopes are organized as an epitopic mosaic distributed around the molecule, showed that each patient displayed a specific anti-C2 epitopic profile, and confirmed the complexity and variability of the immune response against the C2 domain of FVIII. This ability to finely map epitopes could be further used to follow the antibody specificity modifications over time.     

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics anal...     

吸烟对慢性阻塞性肺疾病气道基因表达影响研究新进展

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种具有气流受限特征的可以预防和治疗的疾病,气流受限不完全可逆、呈进行性发展,与肺部对香烟烟雾等有害气体或有害颗粒的异常炎症反应有关。COPD患病率及致残率高,吸烟为目前公认的危险因素,然而仅一部分吸烟者才发展成为...     

Sexual differences in mitochondrial and related proteins in rat cerebral microvessels: A proteomic approach

Sex differences in mitochondrial numbers and function are present in large cerebral arteries, but it is unclear whether these differences extend to the microcirculation. We performed an assessment of mitochondria-related proteins in cerebral microvessels (MVs) isolated from young, male and female, Sprague-Dawley rats. MVs composed of arterioles, capillaries, and venules were isolated from the cerebrum and used to perform a 3 versus 3 quantitative, multiplexed proteomics experiment utilizing tandem mass tags (TMT), coupled with liquid chromatography/mass spectrometry (LC/MS). MS data and bioinformatic analyses were performed using Proteome Discoverer version 2.2 and Ingenuity Pathway Analysis. We identified a total of 1969 proteins, of which 1871 were quantified by TMT labels. Sixty-four proteins were expressed significantly (p < 0.05) higher in female samples compared with male samples. Females expressed more mitochondrial proteins involved in energy production, mitochondrial membrane structure, anti-oxidant enzyme proteins, and those involved in fatty acid oxidation. Conversely, males had higher expression levels of mitochondria-destructive proteins. Our findings reveal, for the first time, the full extent of sexual dimorphism in the mitochondrial metabolic protein profiles of MVs, which may contribute to sex-dependent cerebrovascular and neurological pathologies.