The Osiris family genes function as novel regulators of the tube maturation process in the Drosophila trachea.

Drosophila trachea is a premier model to study tube morphogenesis. After the formation of continuous tubes, tube maturation follows. Tracheal tube maturation starts with an apical secretion pulse that deposits extracellular matrix components to form a chitin-based apical luminal matrix (aECM). This aECM is then cleared and followed by the maturation of taenidial folds. Finally, air fills the tubes. Meanwhile, the cellular junctions are maintained to ensure tube integrity. Previous research has identified several key components (ER, Golgi, several endosomes) of protein trafficking pathways that regulate the secretion and clearance of aECM, and the maintenance of cellular junctions. The Osiris (Osi) gene family is located at the Triplo-lethal (Tpl) locus on chromosome 3R 83D4-E3 and exhibits dosage sensitivity. Here, we show that three Osi genes (Osi9, Osi15, Osi19), function redundantly to regulate adherens junction (AJ) maintenance, luminal clearance, taenidial fold formation, tube morphology, and air filling during tube maturation. The localization of Osi proteins in endosomes (Rab7-containing late endosomes, Rab11-containing recycling endosomes, Lamp-containing lysosomes) and the reduction of these endosomes in Osi mutants suggest the possible role of Osi genes in tube maturation through endosome-mediated trafficking. We analyzed tube maturation in zygotic rab11 and rab7 mutants, respectively, to determine whether endosome-mediated trafficking is required. Interestingly, similar tube maturation defects were observed in rab11 but not in rab7 mutants, suggesting the involvement of Rab11-mediated trafficking, but not Rab7-mediated trafficking, in this process. To investigate whether Osi genes regulate tube maturation primarily through the maintenance of Rab11-containing endosomes, we overexpressed rab11 in Osi mutant trachea. Surprisingly, no obvious rescue was observed. Thus, increasing endosome numbers is not sufficient to rescue tube maturation defects in Osi mutants. These results suggest that Osi genes regulate other aspects of endosome-mediated trafficking, or regulate an unknown mechanism that converges or acts in parallel with Rab11-mediated trafficking during tube maturation.

Correlation of urinary cotinine with cardiovascular risk factors in pan masala tobacco users.

BACKGROUND: Tobacco consumption is considered as one of the major risk factors for cardiovascular (CV) morbidity. However, the effect of paan masala tobacco (PMT) (a type of smokeless tobacco) consumption has not been well studied in our context. Our study is aimed to find an association of CV risk factors between PMT users and nonusers and to correlate those parameters with urinary cotinine level, a degradation product of nicotine occurring in tobacco. METHODS: This comparative cross-sectional study was carried out among 200 participants. The effect of PMT use on CV risk factors such as blood pressure (BP), lipid profile, and body mass index was measured against urine cotinine level. Statistical tests used were χ2 test for categorical variable, independent t-test, Mann-Whitney U test, and Spearman's correlation applied for numerical variable, and multivariate regression analysis was performed as required. The level of significance was set at p < 0.05. RESULT: Mean BP, total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and median cotinine level were found to be significantly higher in PMT users than in controls (p < 0.001). Urinary cotinine level was positively correlated with mean BP, TC, TG, and LDL-C in PMT users (p < 0.001). Similarly, the odds of having hypercholesterolemia and increased diastolic BP was also significantly higher in PMT users (p < 0.001). CONCLUSION: PMT use has an adverse effect on CV risk parameters and there is a rational of cotinine measurement for screening CV risk among PMT users.

Oxidative stress and nutritional status in chronic obstructive pulmonary disease.

BACKGROUND: Oxidative stress and malnutrition are shown to have pathogenic effect in Chronic Obstructive Pulmonary Disease (COPD). AIM: This study was done to assess the burden of oxidative stress in COPD and to determine its relation to their nutritional status. MATERIALS AND METHODS: In this cross-sectional study, 100 COPD cases from emergency and medical ward and meeting inclusion criteria, along with age, sex and occupation (mainly farmers, housewives and drivers) matched 100 controls without COPD and meeting inclusion criteria were enrolled. Oxidative stress was assessed by measuring lipid peroxidation product, Malondialdehyde (MDA) and antioxidants, like Vitamin C, E and Red Blood Cell Catalase (RBCC). Mini Nutritional Assessment (MNA) tool and Body Mass Index (BMI) were used to assess nutritional status. STATISTICAL ANALYSIS: Chi-square test was applied for categorical variable. Student t-test was applied for comparison of means. Analysis of Variance (ANOVA) was applied for comparison between groups followed by Bonferroni post hoc analysis. Pearson correlation method was used for quantitative variables. Statistical significance was defined as p< 0.05 (two tailed). RESULTS: COPD cases had significantly high MDA level with low level of Vitamin E and catalase as compared to controls (p < 0.001). Most of the COPD cases were underweight (BMI ≤ 18.5 Kg/m(2)) and malnourished (MNA score less than 7). Bonferroni post-hoc analysis, showed significantly high burden of oxidative stress in underweight and malnourished cases as compared to normal weight (p < 0.05) among COPD cases. Highly significant correlation was seen between BMI and plasma MDA level (r = -0.27, p = 0.008) in COPD cases. CONCLUSION: This study shows impaired oxidant/antioxidant balance along with malnutrition and underweight in COPD, which signals for considering antioxidant therapy along with nutritional management.