Predicting protein functions by relaxation labelling protein interaction network

<p>Abstract</p> <p>Background</p> <p>One of key issues in the post-genomic era is to assign functions to uncharacterized proteins. Since proteins seldom act alone; rather, they must interact with other biomolecular units to execute their functions. Thus, the functions of unknown proteins may be discovered through studying their interactions with proteins having known functions. Although many approaches have been developed for this purpose, one of main limitations in most of these methods is that the dependence among functional terms has not been taken into account.</p> <p>Results</p> <p>We developed a new network-based protein function prediction method which combines the likelihood scores of local classifiers with a relaxation labelling technique. The framework can incorporate the inter-relationship among functional labels into the function prediction procedure and allow us to efficiently discover relevant non-local dependence. We evaluated the performance of the new method with one other representative network-based function prediction method using E. coli protein functional association networks.</p> <p>Conclusion</p> <p>Our results showed that the new method has better prediction performance than the previous method. The better predictive power of our method gives new insights about the importance of the dependence between functional terms in protein functional prediction.</p

The prevalence of metabolic syndrome and cardiovascular risk factors in adults in southern China

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome has been shown to increase the incidence of cardiovascular disease. Little information exists on the prevalence of the metabolic syndrome for southern Chinese. We therefore investigate the prevalence of the metabolic syndrome in a southern Chinese population with 85 million residents.</p> <p>Methods</p> <p>The Guangdong Nutrition and Health Survey 2002 is a cross-sectional survey designed to assess the health and nutritional status of 85 million residents in Guangdong province located in southern China. Stratified multistage random sampling method was applied in this survey and a provincial representative sample of 6,468 residents aged 20 years or above was obtained in the present study. The participants received a full medical check-up including measurement of blood pressure, obesity indices, fasting lipids and glucose levels. Data describing socioeconomic and lifestyle factors was also collected through interview. Metabolic syndrome was defined in accordance with the International Diabetes Federation criteria.</p> <p>Results</p> <p>The prevalence of metabolic syndrome was 7.30%, translating into a total of 4.0 million residents aged 20 years or above having the condition in this southern Chinese population. The urban population had higher prevalence of the syndrome than the rural population (10.57% vs 4.30%). Females had a higher prevalence of metabolic syndrome than males (8.99% vs 5.27%). More than 60% of the adults had at least one component of the metabolic syndrome.</p> <p>Conclusions</p> <p>Our results indicate that a large proportion of southern Chinese adults have the metabolic syndrome and associated risk factors. The metabolic syndrome has become an important public health problem in China. These findings emphasize the urgent need to develop population level strategies for the prevention, detection, and treatment of cardiovascular risk in China.</p

Unexpected High Digestion Rate of Cooked Starch by the Ct-Maltase-Glucoamylase Small Intestine Mucosal α-Glucosidase Subunit

For starch digestion to glucose, two luminal α-amylases and four gut mucosal α-glucosidase subunits are employed. The aim of this research was to investigate, for the first time, direct digestion capability of individual mucosal α-glucosidases on cooked (gelatinized) starch. Gelatinized normal maize starch was digested with N- and C-terminal subunits of recombinant mammalian maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) of varying amounts and digestion periods. Without the aid of α-amylase, Ct-MGAM demonstrated an unexpected rapid and high digestion degree near 80%, while other subunits showed 20 to 30% digestion. These findings suggest that Ct-MGAM assists α-amylase in digesting starch molecules and potentially may compensate for developmental or pathological amylase deficiencies

HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study

<p>Abstract</p> <p>Background</p> <p>How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE).</p> <p>Methods</p> <p>A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells to sodium fluorescein was measured. The expressions of the occludin and claudins were determined by real-time polymerase chain reaction, immunofluorescence, and Western blot analysis. Activation of ERK1/2 was detected by Western blot analysis with specific antiphospho protein antibodies. NF-κB DNA binding activity was determined by transcription factor assay. Specific pharmacologic inhibitors directed against the MAPKs were used to analyze the signaling involved in barrier destruction of RPE cells exposed to HIV-1 Tat.</p> <p>Results</p> <p>Treating cultured human retinal pigment epithelial cells with 100 nM Tat for 24 hours increased the permeability and decreased the TER of the epithelial monolayer. HIV-1 Tat also disrupted and downregulated the tight-junction proteins claudin-1, claudin-3, and claudin-4 in these cells, whereas claudin-2 was upregulated, and the expression of occludin was unaffected. HIV-1 Tat protein also induced activation of ERK1/2 and NF-κB. HIV-1 Tat protein induced barrier destruction, changes in expression of TJs, and activation of ERK1/2 and NF-κB were abrogated by inhibitor of ERK1/2 and NF-κB.</p> <p>Conclusion</p> <p>HIV-1 Tat protein causes increases in the paracellular permeability of RPE cells in vitro concomitant with changes in expression of certain transmembrane proteins associated with the tight junction. The effects of HIV-1 Tat on barrier function of the RPE may be mediated by ERK MAPK and NF-κB activation, which may represent potential targets for novel therapeutic approaches for the retinopathy induced by HIV infection.</p

Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Limited studies have prospectively examined the role of body mass index (BMI) as a major risk factor for asthma during adolescence. This study investigates whether BMI is associated with increased risk of developing physician-diagnosed asthma during 12-month follow-up among adolescents with undiagnosed asthma-like symptoms at baseline.</p> <p>Methods</p> <p>A total of 4,052 adolescents with undiagnosed asthma-like symptoms at baseline were re-examined after a 12-month follow-up. Asthma cases were considered confirmed only after diagnosis by a physician based on the New England core and International Study of Asthma and Allergies in Childhood (ISAAC) criteria video questionnaires, and accompanying pulmonary function tests. Logistic regression analyses were used to evaluate the relationship of BMI and the risk of acquiring asthma.</p> <p>Results</p> <p>The results indicated that girls with higher BMI were at an increased risk of developing asthma during the 12-month follow-up. The odds ratios for girls developing physician-diagnosed asthma were 1.75 (95% CI = 1.18-2.61) and 1.12 (95% CI = 0.76-1.67), respectively, for overweight and obesity as compared to the normal weight reference group after adjustment for other covariates. A similar relationship was not observed for overweight and obese boys who were also significantly more active than their female counterparts.</p> <p>Conclusions</p> <p>Increased BMI exaggerates the risk of acquiring asthma in symptomatic adolescent females but not in adolescent males. Thus, gender is an important modifier of BMI-related asthma risk. Additional research will be required to determine whether the increased asthma risk results from genetic, physiological or behavioural differences.</p

A cost-effectiveness analysis evaluating endoscopic surveillance for gastric cancer for populations with low to intermediate risk

10.1371/journal.pone.0083959PLoS ONE812-POLN

Smoking, Green Tea Consumption, Genetic Polymorphisms in the Insulin-Like Growth Factors and Lung Cancer Risk

Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR) = 13.16, 95% confidence interval (CI) = 2.96–58.51). Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA)19/(CA)19 and (CA)19/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01–0.44) compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment

Compartmentalized Culture of Perivascular Stroma and Endothelial Cells in a Microfluidic Model of the Human Endometrium

The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-m porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal versus disease-related endometrial microenvironments

The Relationship between Urinary Renin Angiotensin System Markers, Renal and Vascular Function in Adolescents with Type 1 Diabetes

AIMS: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess (1) levels of urinary RAAS components and (2) the association between RAAS components and HbA1c, urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and blood pressure in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). METHODS: Urinary angiotensinogen and ACE2 levels, activity of ACE and ACE2, blood pressure (BP), HbA1c, ACR and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). RESULTS: Urinary levels of all RAAS components were higher in T1D vs. HC (p<0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (p<0.0001, p=0.0003, p=0.003 and p=0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (p<0.0001) and ACE activity (p=0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. CONCLUSIONS: Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared to HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range