Salt Stress Induced Variation in DNA Methylation Pattern and Its Influence on Gene Expression in Contrasting Rice Genotypes

BACKGROUND: Salinity is a major environmental factor limiting productivity of crop plants including rice in which wide range of natural variability exists. Although recent evidences implicate epigenetic mechanisms for modulating the gene expression in plants under environmental stresses, epigenetic changes and their functional consequences under salinity stress in rice are underexplored. DNA methylation is one of the epigenetic mechanisms regulating gene expression in plant's responses to environmental stresses. Better understanding of epigenetic regulation of plant growth and response to environmental stresses may create novel heritable variation for crop improvement. METHODOLOGY/PRINCIPAL FINDINGS: Methylation sensitive amplification polymorphism (MSAP) technique was used to assess the effect of salt stress on extent and patterns of DNA methylation in four genotypes of rice differing in the degree of salinity tolerance. Overall, the amount of DNA methylation was more in shoot compared to root and the contribution of fully methylated loci was always more than hemi-methylated loci. Sequencing of ten randomly selected MSAP fragments indicated gene-body specific DNA methylation of retrotransposons, stress responsive genes, and chromatin modification genes, distributed on different rice chromosomes. Bisulphite sequencing and quantitative RT-PCR analysis of selected MSAP loci showed that cytosine methylation changes under salinity as well as gene expression varied with genotypes and tissue types irrespective of the level of salinity tolerance of rice genotypes. CONCLUSIONS/SIGNIFICANCE: The gene body methylation may have an important role in regulating gene expression in organ and genotype specific manner under salinity stress. Association between salt tolerance and methylation changes observed in some cases suggested that many methylation changes are not "directed". The natural genetic variation for salt tolerance observed in rice germplasm may be independent of the extent and pattern of DNA methylation which may have been induced by abiotic stress followed by accumulation through the natural selection process

Is PTEN loss associated with clinical outcome measures in human prostate cancer?

Inactivating PTEN mutations are commonly found in prostate cancer, resulting in an increased activation of Akt. In this study, we investigate the role of PTEN deletion and protein expression in the development of hormone-refractory prostate cancer using matched hormone-sensitive and hormone-refractory tumours. Fluorescent in situ hybridisation and immunohistochemistry was carried out to investigate PTEN gene deletion and PTEN protein expression in the transition from hormone-sensitive to hormone-refractory prostate cancer utilising 68 matched hormone sensitive and hormone-refractory tumour pairs (one before and one after hormone relapse). Heterogeneous PTEN gene deletion was observed in 23% of hormone sensitive tumours. This increased significantly to 52% in hormone-refractory tumours (P=0.044). PTEN protein expression was observed in the membrane, cytoplasm and the nucleus. In hormone sensitive tumours, low levels of cytoplasmic PTEN was independently associated with shorter time to relapse compared to high levels of PTEN (P=0.028, hazard ratio 0.51 (95%CI 0.27–0.93). Loss of PTEN expression in the nucleus of hormone sensitive tumours was independently associated with disease-specific survival (P=0.031, hazard ratio 0.52, 95%CI 0.29–0.95). The results from this study demonstrate a role for both cytoplasmic and nuclear PTEN in progression of prostate cancer to the hormone-refractory state

Real-time large-scale dense RGB-D SLAM with volumetric fusion

We present a new simultaneous localization and mapping (SLAM) system capable of producing high-quality globally consistent surface reconstructions over hundreds of meters in real time with only a low-cost commodity RGB-D sensor. By using a fused volumetric surface reconstruction we achieve a much higher quality map over what would be achieved using raw RGB-D point clouds. In this paper we highlight three key techniques associated with applying a volumetric fusion-based mapping system to the SLAM problem in real time. First, the use of a GPU-based 3D cyclical buffer trick to efficiently extend dense every-frame volumetric fusion of depth maps to function over an unbounded spatial region. Second, overcoming camera pose estimation limitations in a wide variety of environments by combining both dense geometric and photometric camera pose constraints. Third, efficiently updating the dense map according to place recognition and subsequent loop closure constraints by the use of an ‘as-rigid-as-possible’ space deformation. We present results on a wide variety of aspects of the system and show through evaluation on de facto standard RGB-D benchmarks that our system performs strongly in terms of trajectory estimation, map quality and computational performance in comparison to other state-of-the-art systems.Science Foundation Ireland (Strategic Research Cluster Grant 07/SRC/I1168)Irish Research Council (Embark Initiative)United States. Office of Naval Research (Grant N00014-10-1-0936)United States. Office of Naval Research (Grant N00014-11-1-0688)United States. Office of Naval Research (Grant N00014-12-1-0093)United States. Office of Naval Research (Grant N00014-12-10020)National Science Foundation (U.S.) (Grant IIS-1318392

Health Outcomes and Policy in India

After reviewing health outcomes and policy in India, this chapter concludes that there are at least six sets of issues to be addressed with regard to improving the quantity and quality of health services, and ipso facto improving health outcomes, in India. First, the amount of resources earmarked for health needs to increase. Second, health resources need to be used in a fair and just manner and, in particular, complaints relating to egregious health outcomes need to be addressed. Predominant in this set of issues is oversight and regulation of private sector health provision. The third set of issues relates to the allocation of health resources and, in particular, to the imbalance in the allocation of health resources between towns and villages. A fourth issue is the accessibility of rural areas since it is the most remote areas that have the lowest density of health workers. Another issue is the more efficient use of health workers in order to make them more productive. Finally, Indian health policy is stronger on rhetoric and aspiration than it is on action and implementation. The successful implementation of policy requires the explicit recognition that objectives are often competing (primary versus tertiary care) and the acknowledgement that, with budgetary constraints, one cannot have more of one without having less of the other. The first role of policy is to then choose the optimal mix of objectives with respect to these trade-offs. Secondly, policies come up against vested interests which agitate (often with the support of opposition politicians) and litigate against proposed changes. Lastly, policies in India are made against a background of poor governance with the predatory presence of corruption looming over every policy initiative. In implementing, rather than simply articulating, policy it is important to address these governance issue

Plasma irisin is elevated in type 2 diabetes and is associated with increased E-selectin levels

BACKGROUND: Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM). METHODS: This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL). RESULTS: Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p < 0.001). Moreover, plasma irisin displayed a positive correlation with body mass index (p = 0.04), body fat percentage (p = 0.03), HbA1c (p = 0.03) and soluble E-selectin (p < 0.001). A significant negative association was observed between plasma irisin and visceral adiposity (p = 0.006) in T2DM patients. Multiple regression analysis revealed that circulating soluble E-selectin levels could be predicted by plasma irisin (p = 0.004). Additionally, cultured human umbilical vein endothelial cells (HUVEC) exposed to 200 ng/ml irisin for 4 h showed a significant fourfold increase in E-selectin and 2.5-fold increase in ICAM-1 gene expression (p = 0.001 and p = 0.015 respectively), and there was a 1.8-fold increase in soluble E-selectin in conditioned media (p < 0.05). CONCLUSION: These data suggest that elevated plasma irisin in T2DM is associated with indices of adiposity, and that irisin may be involved in pro-atherogenic endothelial disturbances that accompany obesity and T2DM. Accordingly, irisin may constitute a potentially novel therapeutic opportunity in the field of obesity and cardiovascular diabetology