Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin −0.7 ± 0.7%, p ≤ 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 ± 14.5 μmol glucose/min/kg free fat mass, p < 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p ≤ 0.05) with RSG (2.1 ± 2.0 kg and 1.4 ± 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 ± 28.7 cm², p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (−6.7 ± 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.     

Detection of hard and soft selective sweeps from Drosophila melanogaster population genomic data

Whether hard sweeps or soft sweeps dominate adaptation has been a matter of much debate. Recently, we developed haplotype homozygosity statistics that (i) can detect both hard and soft sweeps with similar power and (ii) can classify the detected sweeps as hard or soft. The application of our method to population genomic data from a natural population of Drosophila melanogaster (DGRP) allowed us to rediscover three known cases of adaptation at the loci Ace, Cyp6g1, and CHKov1 known to be driven by soft sweeps, and detected additional candidate loci for recent and strong sweeps. Surprisingly, all of the top 50 candidates showed patterns much more consistent with soft rather than hard sweeps. Recently, Harris et al. 2018 criticized this work, suggesting that all the candidate loci detected by our haplotype statistics, including the positive controls, are unlikely to be sweeps at all and that instead these haplotype patterns can be more easily explained by complex neutral demographic models. They also claim that these neutral non-sweeps are likely to be hard instead of soft sweeps. Here, we reanalyze the DGRP data using a range of complex admixture demographic models and reconfirm our original published results suggesting that the majority of recent and strong sweeps in D. melanogaster are first likely to be true sweeps, and second, that they do appear to be soft. Furthermore, we discuss ways to take this work forward given that most demographic models employed in such analyses are necessarily too simple to capture the full demographic complexity, while more realistic models are unlikely to be inferred correctly because they require a large number of free parameters.     

Prevalence and Associated Factors for Pterygium in Rural Agrarian Central India. The Central India Eye and Medical Study

Purpose

To evaluate the prevalence of pterygia and associated factors in a rural population in a mostly undeveloped agrarian region.

Methods

The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects (aged 30+ years). A detailed ophthalmic and medical examination was performed. A pterygium was diagnosed during the slit lamp examination and confirmed on corneal photographs. It was defined as a fleshy fibrovascular growth, crossing the limbus and typically seen on the nasal, and sometimes temporal, conjunctiva.

Results

A pterygium was detected in 798 eyes (prevalence rate: 8.47±0.29%) of 608 (12.91±0.49%) subjects. Bilateral pterygia were present in 190 subjects (4.0% of study population). Pterygia prevalence increased from 6.7±0.8% in the age group 30-39 years, to 13.5±1.2% in the age group 50-59 years, to 25.3±2.1% in the age group 70-79 years. Prevalence of pterygia was associated with older age (P<0.001; regression coefficient B: 0.02; odds ratio (OR): 1.02; 95%CI: 1.01, 1.03), male gender (P<0.001;B:-0.73;OR: .48;95%CI:0.39,0.61), lower level of education (P<0.001;B:-0.30;OR:0.74;95%CI:0.69,0.80), lower body height (P=0.001;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.26;95%CI:1.18,1.34). If the education level was dropped, the number of hours spent with vigorous activity outdoors (P=0.001;B:0.001;OR:1.001;95%CI:1.000,1.0001) was significantly associated with the prevalence of pterygia, in addition to older age (P<0.001;B:0.03;OR:1.03;95%CI:1.03,1.04), male gender (P<0.001;B:-0.49;OR:0.62;95%CI:0.49,0.77), lower body height (P=0.005;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.25;95%CI:1.18,1.34).

Conclusions

Pterygium prevalence in rural Central India is about 13% among adult Indians aged 30+ years. Older age, male gender, lower educational level, lower body height and more time spent outdoors with vigorous work were associated factors. Since the living conditions in the study location were mostly untouched by modern developments, the results may show the prevalence and associations of pterygia without major medical or technologic influences.     

Structure prediction and binding sites analysis of curcin protein of Jatropha curcas using computational approaches

Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher-plant species that are directly targeted toward herbivores. Jatropha curcas is one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction of oil, is rich in curcin, a highly toxic RIP similar to ricin, which makes it unsuitable for animal feed. Although the toxicity of curcin is well documented in the literature, the detailed toxic properties and the 3D structure of curcin has not been determined by X-ray crystallography, NMR spectroscopy or any in silico techniques to date. In this pursuit, the structure of curcin was modeled by a composite approach of 3D structure prediction using threading and ab initio modeling. Assessment of model quality was assessed by methods which include Ramachandran plot analysis and Qmean score estimation. Further, we applied the protein-ligand docking approach to identify the r-RNA binding residue of curcin. The present work provides the first structural insight into the binding mode of r-RNA adenine to the curcin protein and forms the basis for designing future inhibitors of curcin. Cloning of a future peptide inhibitor within J. curcas can produce non-toxic varieties of J. curcas, which would make the seed-cake suitable as animal feed without curcin detoxification.     

Oral health‐related quality of life and nutritional status of institutionalized elderly population aged 60 years and above in Mysore City,India

doi: 10.1111/j.1741‐2358.2012.00651.x Oral health‐related quality of life and nutritional status of institutionalized elderly population aged 60 years and above in Mysore City, India Objective: To assess whether oral health–related quality of life (OHRQoL) is associated with nutritional status in the institutionalised elderly population of Mysore. Background: Malnutrition in the elderly has an evident impact on their general health and quality of life. Analysis of data of the Geriatric Oral Health Assessment Index (GOHAI) and their association with the Mini Nutritional Assessment (MNA) results improves our understanding of the complex relationship between oral health and malnutrition. Materials and methods: The study was conducted among the institutionalised elderly population in Mysore city, Karnataka. Data on socio‐demographic, oral health status were gathered. OHRQoL was evaluated using GOHAI, and malnutrition risk using MNA. Results: Out of 141 elderly, 41.1% were men and 58.9% were women with mean age of 72.2 ± 7.5 years. Mean GOHAI score was 47.03 ± 9.2, with 69.5% had low perception of oral health. Mean MNA score was 9.91 ± 2.4, 15.6% were malnourished, 52.5% were at risk of malnutrition and 31.9% were adequately nourished. A strong association was found between the mean GOHAI and MNA scores. Conclusion: Oral health–related quality of life was associated with nutritional deficit, and it requires a greater integration between dentistry and nutrition in the health promotion of older adults.     

Recent Selective Sweeps in North American Drosophila melanogaster Show Signatures of Soft Sweeps

Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.     

Mining the metagenome of activated biomass of an industrial wastewater treatment plant by a novel method

Metagenomic libraries herald the era of magnifying the microbial world, tapping into the vast metabolic potential of uncultivated microbes, and enhancing the rate of discovery of novel genes and pathways. In this paper, we describe a method that facilitates the extraction of metagenomic DNA from activated sludge of an industrial wastewater treatment plant and its use in mining the metagenome via library construction. The efficiency of this method was demonstrated by the large representation of the bacterial genome in the constructed metagenomic libraries and by the functional clones obtained. The BAC library represented 95.6 times the bacterial genome, while, the pUC library represented 41.7 times the bacterial genome. Twelve clones in the BAC library demonstrated lipolytic activity, while four clones demonstrated dioxygenase activity. Four clones in pUC library tested positive for cellulase activity. This method, using FTA cards, not only can be used for library construction, but can also store the metagenome at room temperature.