Secular trends in prevalence of overweight and obesity from 2006 to 2009 in urban asian Indian adolescents aged 14-17 years

The present study examines the secular trends in prevalence of overweight and obesity among urban Asian Indian adolescents in New Delhi (North India). The data were derived from cross-sectional sampling of children, 3493 in year 2006 and 4908 in year 2009, aged 14-17 years studying in privately-funded and government-funded schools. Age, gender and Asian Indian-specific cut offs of body mass index (BMI) were used to define overweight and obesity. The prevalence of obesity increased significantly from 9.8% in 2006 to 11.7% in 2009 (p<0.01), whereas underweight decreased from 11.3% to 3.9% (p<0.001). There was a significantly higher risk of being overweight (OR 1.28; 95% CI, 1.15-1.42) and obese (OR 1.44; 95% CI, 1.24-1.66) in year 2009 than 2006, after adjusting for age, gender and type of school. Males and privately-funded school children had significantly higher increase in prevalence and risk of being overweight and obese over the three years. In conclusion, this study showed an increasing trend in prevalence of overweight and obesity in urban Asian Indian adolescents. More specifically, the study showed the association of this increasing trend of overweight and obesity prevalence with male gender and high socio-economic status, calling for an urgent need for immediate and targeted preventive measures.     

Genome-Wide Comparative in silico Analysis of Calcium Transporters of Rice and Sorghum

The mechanism of calcium uptake, translocation and accumulation in Poaceae has not yet been fully understood. To address this issue, we conducted genome-wide comparative in silico analysis of the calcium (Ca2+) transporter gene family of two crop species, rice and sorghum. Gene annotation, identification of upstream cis-acting ele- ments, phylogenetic tree construction and syntenic mapping of the gene family were performed using several bio- informatics tools. A total of 31 Ca2+ transporters, distributed on 9 out of 12 chromosomes, were predicted from rice genome, while 28 Ca2+ transporters predicted from sorghum are distributed on all the chromosomes except chromosome 10 (Chr 10). Interestingly, most of the genes on Chr 1 and Chr 3 show an inverse syntenic relation- ship between rice and sorghum. Multiple sequence alignment and motif analysis of these transporter proteins re- vealed high conservation between the two species. Phylogenetic tree could very well identify the subclasses of channels, ATPases and exchangers among the gene family. The in silico cis-regulatory element analysis suggested diverse functions associated with light, stress and hormone responsiveness as well as endosperm- and meris- tem-specific gene expression. Further experiments are warranted to validate the in silico analysis of the predicted transporter gene family and elucidate the functions of Ca2+ transporters in various biological processes.     

Influence of language and ancestry on genetic structure of contiguous populations: A microsatellite based study on populations of Orissa

Background

Although cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines of Cftr deficient mice (CF mice: Cftr ^tm1Unc ) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.

Results

CF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.

Conclusion

Potential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype.     

Crystal structures of the PNA-porphyrin complex in the presence and absence of lactose: mapping the conformational changes on lactose binding, interacting surfaces, and supramolecular aggregations

The extraordinary recognition specificity of lectins for carbohydrate ligands appears to be violated as they also bind to porphyrins and other noncarbohydrate ligands. In this study, crystal structures of meso-tetrasulfonatophenylporphyrin (H(2)TPPS) bound to peanut agglutinin (PNA) in the presence and absence of lactose were determined. The binding of H(2)TPPS with PNA involved 11 molecules of H(2)TPPS in different supramolecular stacking arrangements associated with a tetramer of PNA in the crystals of the PNA-H(2)TPPS binary complex as well as the PNA-H(2)TPPS-lactose ternary complex. The ternary complex involved lactose binding only to two subunits of the PNA tetramer, which did not have porphyrin interacting in the vicinity of the carbohydrate-binding site. Comparison of the two structures highlighted the plasticity of the carbohydrate-binding site expressed in terms of the conformational change in lactose binding. The unusual quaternary structure of PNA, which results in exposed protein-protein interaction sites, might be responsible for the porphyrin binding. The association of porphyrin in diverse oligomeric stacking arrangements observed in the PNA-H(2)TPPS complex suggested the possibility of protein-porphyrin aggregation under abnormal physiological conditions. The structures described here provide a possible native conformation of the carbohydrate-binding site of PNA in the absence of the ligand, highlight mapping of the unsaturated binding surfaces of PNA using porphyrin interactions, indicate new leads toward possible application of this lectin in photodynamic therapy, and exhibit diverse modes of porphyrin-lectin interactions with implications to porphyria, a disease that results from abnormal accumulation of porphyrins.     

Nucleic acid amplification of Mycobacterium tuberculosis complex DNA from archival fine needle aspiration smear scrapings vs. fresh fine needle aspirates of tuberculous lymphadenitis

OBJECTIVE: To assess the efficacy of the nucleic acid amplification (NAA) technique for Mycobacterium tuberculosis (MTB) complex from archival fine needle aspirate (FNA) smear scrapings of confirmed cases of extrapulmonary tuberculosis (EPTB) for a retrospective diagnosis of EPTB as compared to NAA from fresh FNA material from the same cases. STUDY DESIGN: Smear scrapings from 51 cases; 33 cases of tuberculous lymphadenitis (from patients who had undergone NAA 1 year before for MTB from fresh FNA material); 13 negative controls from nontuberculous, archival FNA smears; and 5 known acid-fast bacilli (AFB)-positive sputum smears, were subjected to NAA using the IS6110 primer sequence of M tuberculosis. Ziehl-Neelsen staining was done in all the smears. RESULTS: Of the 33 cases of tuberculous lymphadenitis, 15 (45.4%) were AFB positive and 18 (64.5%) AFB negative. MTB NAA was positive in 73.3% (11 of 15 AFB-positive cases) in the freshly aspirated material and was observed in 60% (9 of 15 AFB-positive cases) when done on DNA extracted from the archival smear scrapings of the same cases. Similarly, in the 18 AFB-negative cases, MTB NAA positivity was 72.2% (13 of 18) on fresh material and 44.4% (8 of 18) on archival smear scrapings from the same AFB-negative cases. Overall NAA positivity was 51.5% for archival smear scrapings as compared to 71% for fresh FNA of the same cases. CONCLUSION: Low NAA sensitivity of MTB DNA in archival material of known tuberculous cases limits the routine use of NAA based retrospective molecular diagnosis of MTB complex.     

eQTL Explorer: integrated mining of combined genetic linkage and expression experiments

The development of computational resources to visualize and explore data from combined genome-wide expression and linkage studies is essential for the development of testable hypotheses. eQTL Explorer stores expression profiles, linkage data and information from external sources in a relational database and enables simultaneous visualization and intuitive interpretation of the combined data via a Java graphical interface. eQTL Explorer provides a new and powerful tool to interrogate these very large and complex datasets.     

An arousing, musically enhanced bird song stimulus mediates circadian rhythm phase advances in dim light

A musically enhanced bird song stimulus presented in the early subjective night phase delays human circadian rhythms. This study determined the phase-shifting effects of the same stimulus in the early subjective day. Eleven subjects (ages 18-63 yr; mean +/- SD: 28.0 +/- 16.6 yr) completed two 4-day laboratory sessions in constant dim light (<20 lux). They received two consecutive presentations of either a 2-h musically enhanced bird song or control stimulus from 0600 to 0800 on the second and third mornings while awake. The 4-day sessions employing either the stimulus or control were counterbalanced. Core body temperature (CBT) was collected throughout the study, and salivary melatonin was obtained every 30 min from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Dim light melatonin onset and CBT minimum circadian phase before and after stimulus or control presentation was assessed. The musically enhanced bird song stimulus produced significantly larger phase advances of the circadian melatonin (mean +/- SD: 0.87 +/- 0.36 vs. 0.24 +/- 0.22 h) and CBT (1.08 +/- 0.50 vs. 0.43 +/- 0.37 h) rhythms than the control. The stimulus also decreased fatigue and total mood disturbance, suggesting arousing effects. This study shows that a musically enhanced bird song stimulus presented during the early subjective day phase advances circadian rhythms. However, it remains unclear whether the phase shifts are due directly to effects of the stimulus on the clock or are arousal- or dim light-mediated effects. This nonphotic stimulus mediates circadian resynchronization in either the phase advance or delay direction.     

Manipulation of cellular redox parameters for improving therapeutic responses in B-cell lymphoma and multiple myeloma

Developing novel combined-modality therapeutic approaches based on understanding of the involvement of redox biology in apoptosis of malignant cells is a promising approach for improving clinical responses in B-cell lymphoma and multiple myeloma. Therapeutic modalities that generate reactive oxygen species (i.e., radiation, photodynamic therapy, and specific chemotherapeutic drugs) have been shown to be selectively cytotoxic to malignant B-cells. In this review, we will discuss agents that induce apoptosis in B-cell tumors by oxidative stress. Subsequently, a novel biochemical rationale (based on fundamental differences in cancer vs. normal cell oxidative metabolism) for combining oxidative stressors with radiotherapy and chemotherapy, that may lead to designing of more effective treatment strategies for B-cell malignancies, will be discussed. Besides providing potential curative benefit, such novel therapies could also selectively target and inhibit the emergence of drug-resistance in tumor cells, which is a major determinant of treatment failure in many B-cell malignancies.     

Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts

A canonical Wnt signal maintains adult mammary ductal stem cell activity, and this signal requires the Wnt signaling reception, LRP5. However, previous data from our laboratory have shown that LRP5 and LRP6 are co-expressed in mammary basal cells and that LRP6 is active, leading us to question why LRP6 is insufficient to mediate canonical signaling in the absence of LRP5. Here, we show that at endogenous levels of LRP5 and LRP6 both receptors are required to signal in response to some Wnt ligands both in vitro (in mouse embryonic fibroblasts and mammary epithelial cells) and in vivo (in mammary outgrowths). This subgroup of canonical ligands includes Wnt1, Wnt9b, and Wnt10b; the latter two are expressed in mammary gland. In contrast, the ligand commonly used experimentally, Wnt3a, prefers LRP6 and requires just one receptor regardless of cellular context. When either LRP5 or LRP6 is overexpressed, signaling remains ligand-dependent, but the requirement for both receptors is abrogated (regardless of ligand type). We have documented an LRP5-6 heteromer using immiscible filtration assisted by surface tension (IFAST) immunoprecipitation. Together, our data imply that under physiological conditions some Wnt ligands require both receptors to be present to generate a canonical signal. We have designed a model to explain our results based on the resistance of LRP5-6 heteromers to a selective inhibitor of E1/2-binding Wnt-LRP6 interaction. These data have implications for stem cell biology and for the analysis of the oncogenicity of LRP receptors that are often overexpressed in breast tumors.     

Molecular cloning and expression profile of snow trout GPDH gene in response to abiotic stress

Glycerol-3-phosphate dehydrogenase (GPDH) gene possibly plays a key role for cold acclimation process in snow trout during winter months when water temperature goes down to 4–5?°C. In this study, 1,012?bp nucleotide fragment of GPDH gene was obtained from two snow trout species (Schizothorax richardsonii and S. niger; family: Cyprinidae), distributed in several Himalayan rivers. The gene encoded a protein of 334 amino acids. The encoded protein sequence was very similar to GPDH of Danio rerio (94.36?%) using BLASTx searches. In S. richardsonii the qRT-PCR showed highest expression in muscle tissue followed by liver and also revealed 19 fold gene expression in liver tissue under cold (5?°C) in comparison with warm (15?°C) condition. The elevated expression levels of GPDH cDNA on cold treatment furthermore suggest that GPDH plays a role in stress related responses in S. richardsonii. The phylogenetic analysis showed that the two snow trout species GPDH share the same clade with characterized GPDHs from other teleost fishes suggesting a common evolutionary origin and a similar catalytic function. In addition, the Ka/Ks ratios of these sequences suggested that they are under purifying selection. Moreover, the expression profile of GPDH gene among co generic species of genus Schizothorax showed that GPDH cDNA expression was highest in S. richardsonii and lowest in S. esocinus which gives an indication of species specific adaptation in relation to different geographical areas.