Aortic Elasticity is Impaired in Patients with Endemic Fluorosis

Sixty-three patients with endemic fluorosis (36 males/27 females; mean age 33.9 ± 8.6 years) and 45 age-, sex-, and body mass index-matched healthy controls (30 males/15 females; mean age 32.7 ± 8.8 years) were included in this study. Aortic stiffness indices, aortic strain (AS), aortic distensibility (AD), and aortic strain index (ASI) were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.9 ± 0.1 mg/l vs. 0.4 ± 0.1 mg/l, respectively; P < 0.001). AS and AD were significantly lower in fluorosis patients than in the controls (for AS 5.3 ± 3.6 vs. 8.0 ± 3.4%; P < 0.001 and for AD 0.2 ± 0.1 vs. 0.3 ± 0.1 cm² dyn⁻¹ 10⁻³; P < 0.001, respectively). In contrast, signicantly higher ASI was observed in fluorosis patients than in the controls (3.4 ± 0.6 vs. 3.0 ± 0.4; P < 0.001, respectively). The results of our study demonstrate that elastic properties of ascending aorta are impaired in patients with endemic fluorosis.     

Integrated protein network and microarray analysis to identify potential biomarkers after myocardial infarction

A significant proportion of patients develop left ventricular (LV) dysfunction and heart failure (HF) after acute myocardial infarction (MI). Existing biomarkers of HF provide limited information after MI. To identify new prognostic biomarkers in MI patients, we designed an approach combining protein interaction networks and microarray analysis of blood cells. Blood samples for RNA and protein analysis were taken from 127 acute MI patients. Echocardiography was performed at one month. Assuming that angiogenesis is related to cardiac repair after MI, a protein-protein interaction network of angiogenesis was constructed and analyzed. Among the 556 proteins and 686 interactions of this network, a cluster of 53 proteins highly specialized in regulation of cell growth was identified. Of these 53 proteins, 38 were found differentially expressed by microarrays between low (≤ 40%) and high (>40%) LV ejection fraction (EF) patients (n = 32). Among these 38 genes, prediction analysis identified a set of three genes able to predict significant LV dysfunction (EF ≤ 40%) with an area under the receiver operating characteristic curve (AUC) of 0.82. These three genes—vascular endothelial growth factor B, thrombospondin-1 and placental growth factor—had a stronger predictive value than brain natriuretic peptide and troponin T (AUC of 0.63). Independent validations on protein expression and quantitative PCR datasets confirmed the results. In conclusion, a new strategy is described that allows identifying new potential biomarkers. The three specific biomarkers described here remain to be validated in a larger patient population.     

Atopic dermatitis in West Highland white terriers is associated with a 1.3-Mb region on CFA 17

Canine atopic dermatitis (AD) is an allergic inflammatory skin disease that shares similarities with AD in humans. Canine AD is likely to be an inherited disease in dogs and is common in West Highland white terriers (WHWTs). We performed a genome-wide association study using the Affymetrix Canine SNP V2 array consisting of over 42,800 single nucleotide polymorphisms, on 35 atopic and 25 non-atopic WHWTs. A gene-dropping simulation method, using SIB-PAIR, identified a projected 1.3 Mb area of association (genome-wide P = 6 × 10⁻⁵ to P = 7 × 10⁻⁴) on CFA 17. Nineteen genes on CFA 17, including 1 potential candidate gene (PTPN22), were located less than 0.5 Mb from the interval of association identified on the genome-wide association analysis. Four haplotypes within this locus were differently distributed between cases and controls in this population of dogs. These findings suggest that a major locus for canine AD in WHWTs may be located on, or in close proximity to an area on CFA 17.     

Hippocampal CA1 Pyramidal Cell Size is Reduced in Bipolar Disorder

1. Schizophrenia and bipolar disorder are neurodevelopmental disorders with significant genetic vulnerabilities. Several trophic genes and/or proteins have been implicated in the causation for both disorders. 2. We hypothesized that these genes and/or proteins may impact neuronal growth in both disorders. 3. Hippocampal tissue sections from CA1 area of schizophrenic, bipolar, depressed, and controls subjects, matched for age, sex, PMI, drug exposure, and brain pH were prepared for cell size determination using the Stanley Medical Research Foundation postmortem brain collection. 4. Quantification of hippocampal CA1 pyramidal neuron size showed a significant 12% reduction in cell size (p < 0.05) in bipolar subjects vs. controls. There were nonsignificant trends for reduction in cell size in both schizophrenic and depressed subjects vs. controls. 5. These results indicate for the first time that pyramidal cell atrophy is present in hippocampus of subjects with bipolar disorder.     

Construction of a Full-Length cDNA Library and Analysis of Expressed Sequence Tags from Inflorescence of Apomictic Sabaigrass (Eulaliopsis binata)

Eulaliopsis binata, which is a close relative of cereal crops, was recognized as an important research material owing to its high frequency of apospory and autonomous endosperm formation. However, little information is known about its genomics and regulatory pathway participating in reproductive development. For the first step to understand molecular basis in sabaigrass (E. binata), a SMART complementary DNA library from the inflorescence tissue was constructed and characterized. The titers of original and amplified libraries were 5.53 × 10⁶ and 1.49 × 10¹⁰ pfu/ml, respectively. The percentage of recombinants was 96% in the original library. Analysis of sequencing results of 398 out of 437 randomly picked clones showed that 271 (68.1%) expressed sequence tags (ESTs) exhibited significant similarity with known putative functional nucleotide sequences in the GenBank databases, 25 (6.3%) ESTs have significant matches with hypothetical proteins, putative proteins, and unknown proteins, and the other 25.6% ESTs had no significant similarity to sequences in the public databases. Based on molecular function of GO annotation, the four most abundant terms are nucleotide binding, hydrolase activity, ion binding, and protein binding, and these genes were involved in 61 different pathways using the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Besides, simple sequence repeats detection in 398 ESTs was carried out, and several genes were chosen to perform expression analysis. This report represents a first step in expanding molecular-genetic analyses in E. binata and can be used to optimally mine useful information from a relatively small data set.     

Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii, during short-term exposure to irradiance stress reveals significant down regulation of several heat-shock proteins

Oxygenic photosynthetic organisms often suffer from excessive irradiance, which cause harmful effects to the chloroplast proteins and lipids. Photoprotection and the photosystem II repair processes are the mechanisms that plants deploy to counteract the drastic effects from irradiance stress. Although the protective and repair mechanisms seemed to be similar in most plants, many species do confer different level of tolerance toward high light. Such diversity may originate from differences at the molecular level, i.e., perception of the light stress, signal transduction and expression of stress responsive genes. Comprehensive analysis of overall changes in the total pool of proteins in an organism can be performed using a proteomic approach. In this study, we employed 2-DE/LC–MS/MS-based comparative proteomic approach to analyze total proteins of the light sensitive model unicellular green alga Chlamydomonas reinhardtii in response to excessive irradiance. Results showed that among all the differentially expressed proteins, several heat-shock proteins and molecular chaperones were surprisingly down-regulated after 3–6 h of high light exposure. Discussions were made on the possible involvement of such down regulation and the light sensitive nature of this model alga.     

Protective Effects of Selenium and Vitamin E Combination on Experimental Colitis in Blood Plasma and Colon of Rats

Ulcerative colitis increases oxidative damage accompanied by production of free oxygen radicals. Selenium (Se) and vitamin E are two natural antioxidants. The present study was undertaken to investigate the possible protective role of Se and vitamin E combination in experimental colitis induced by acetic acid (AA) in rats. This study was carried out on three groups, namely the first (control), the second (experimental colitis group, 2 ml 5% acetic acid), and the third groups (2 ml 5% acetic acid, vitamin E (100 mg/kg body weight (bw)) plus Se (0.2 mg/kg bw)). The activities of catalase (CAT), prolidase (PRS), myeloperoxidase (MPO), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), total thiol (T-SH) were determined in plasma and colon samples. Macroscopic and microscopic damages in colon were increased by AA treatment (p < 0.01 and p < 0.01, respectively), whereas they were decreased by selenium and vitamin E treatment (p < 0.05 and p < 0.01, respectively). The activities of CAT and PRS in the plasma and colon were significantly affected (p < 0.05 and p < 0.01) by treatment of AA, Se, and vitamin E. MPO activity in colon was increased (p < 0.01) by AA treatment and decreased (p < 0.05) by Se and vitamin E administration. The values of TOS and OSI in plasma were increased (p < 0.5) by AA. The TAC and T-SH in colon were decreased (p < 0.05) by AA and increased (p < 0.05) by Se and vitamin E. Based upon these results, Se and vitamin E may play an important role in preventive indication of the oxidative damage associated by acetic acid caused inflammation.     

Enhanced mitochondrial complex gene function and reduced liver size may mediate improved feed efficiency of beef cattle during compensatory growth

Growing ruminants under extended dietary restriction exhibit compensatory growth upon ad libitum feeding, which is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentrations of metabolic hormones. To identify mechanisms contributing to these physiological changes, 8-month-old steers were fed either ad libitum (control; n = 6) or 60–70% of intake of control animals (feed-restricted; n = 6) for a period of 12 weeks. All steers were fed ad libitum for the remaining 8 weeks of experimentation (realimentation). Liver was biopsied at days −14, +1, and +14 relative to realimentation for gene expression analysis by microarray hybridization. During early realimentation, feed-restricted steers exhibited greater rates of gain and feed efficiency than controls and an increase in expression of genes functioning in cellular metabolism, cholesterol biosynthesis, oxidative phosphorylation, glycolysis, and gluconeogenesis. Gene expression changes during feed restriction were similar to those reported in mice, indicating similar effects of caloric restriction across species. Based on expression of genes involved in cell division and growth and upregulation of genes encoding mitochondrial complex proteins in early realimentation, it was concluded that reduced hepatic size and increased mitochondrial function may contribute to improved feed efficiency observed during compensatory growth.     

Oligonucleotide-based Analysis of Differentially Expressed Genes in Hippocampus of Transgenic Mice Expressing NSE-controlled APPsw

The complexity of Alzheimer’s disease (AD) has made it difficult to examine its underlying mechanisms. A gene microarray offers a solution to the complexity through parallel analysis of most of the genes expressed in the hippocampal tissues from AD-transgenic and age-matched control littermates. This study examined the potential effect of APPsw over-expression on the modulation of genes for AD. To accomplish this, an oligonucleotide array was used with the large-scale screening of the hippocampus mRNA from 12-month-old APPsw-transgenic and control mice. There was a total of 116 differentially expressed genes, 59 up-regulated and 57 down-regulated, in the hippocampal region of the transgenic mice compared with the control mice. Initially, two of each of the down-regulated (Xlr3b and Mup3) and up-regulated genes (Serpina9 and Ccr6) were chosen for further investigation if the magnitude of change in these genes on the oligonucleotide array would correspond to those in the RT-PCR analysis from APPsw-transgenic mice. We also found that the changes in the differentially expressed genes are reliable. Thus, these genes might associate with AD neuropathology in neurodegenerative process of AD, although relevance of long lists altered genes should be evaluated in a future study.     

iTRAQ联用串联质谱鉴定食管鳞状细胞癌差异表达蛋白质及蛋白质相互作用网络

基于质谱的蛋白质组学结果不仅具有重复性差和覆盖率低等缺陷,并且针对数十至百个差异表达蛋白质分子的分析非常具有挑战性,而蛋白质与蛋白质相互作用网络（protein-protein interaction network, PPIN）分析能够在一定程度上弥补上述不足,使各种组学研究结果具有一致性和可比性。本研究应用同位素标记相对和绝对定量（iTRAQ）联用串联质谱技术鉴定了与食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）相关的差异表达蛋白质244个（ESCC中,升高和降低的蛋白质分别为119个和125个）,基因本体论（gene ontology, GO）富集与肿瘤十大特征相关的17个GO条目|以该17个条目包含的117个蛋白质为种子蛋白搜索STRING（http: //www.string-db.org）数据库,构建包含96个存在相互作用的PPIN和21个离散蛋白质。用CytoHubba算法确定34个中心节点蛋白质和36个瓶颈蛋白质,非重复49个中心节点和/或瓶颈蛋白质中含7个目前已报道的癌基因表达蛋白（PPP2R1A、CTNNB1、ENO1、EZR、TPM4、COL1A1、TPM3）,确定与该7个癌蛋白直接相互作用的4个蛋白质（FN1、ITGB1、TAGLN和YWHAZ）可能为参与食管癌变的关键蛋白质,并应用Western印迹实验验证了 FN1、ITGB1、TAGLN和YWHAZ等4个关键蛋白质在ESCC中具有显著的表达差异,表明PPIN分析是确定具有重要生物学意义分子的有效途经之一。     

Selenium Levels in First-Degree Relatives of Diabetic Patients

The present study was conducted to evaluate the serum selenium levels in first-degree relatives of diabetic patients (FDR) according to controls. Insulin resistance, serum lipid levels, inflammation markers, and blood pressure were also studied in these patients. Serum levels of selenium in FDR were significantly lower than control group (74.65 ± 5.9 vs 88.7 ± 8.7 μg/dl, p < 0.0001). HsCRP, HOMA-IR, insulin, homocysteine levels were significantly higher in FDR according to the control group (1.32 ± 0.9 vs 0.63 ± 0.4 mg/dL, p < 0.0001; 2.07 ± 0.84 vs 1.51 ± 0.69, p < 0.0001; 9.26 ± 3.8 vs 6.8 ± 2.98 μU/MI, p < 0.0001; 15.7 ± 7.4 vs 11.5 ± 5.1 μmol/L, p < 0.0001, respectively). There was significant correlation between selenium levels and hsCRP (r = − 0.450, p < 0.0001). There was also weak significant correlation also between HOMA-IR and selenium levels (r = −0.227, p = 0.003). There was a correlation between systolic blood pressure and BMI (r = 0.365, p < 0.0001). But there was no correlation between selenium levels and blood pressure or other parameters. HsCRP, HOMA-IR, homocysteine levels in individuals with selenium levels < 80 μg/L (n = 78) was significantly higher than hsCRP HOMA-IR, homocysteine levels in individuals with selenium levels ≥ 80 (n = 91; 1.23 ± 0.98 vs 0.81 ± 0.76 mg/dL, p < 0.003; 1.99 ± 0.88 vs 1.64 ± 0.74, p < 0.005; 15.0 ± 7.6 vs 12.9 ± 5.7 μmol/L, p < 0.049, respectively). Selenium deficiency may contribute to cardiovascular disease risk in FDR.