Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere organization in neonatal rat cardiomyocytes

Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to hypertrophic response. Hypertrophic hallmarks such as cell size and [3H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1 was transfected for 8 h. The finding that cardiac hypertrophy was induced long after increase of sarcomere organization indicates that the promoted sarcomere organization may be one of the crucial factors causing hypertrophy. Furthermore, when MR-1 was transfected into cardiomyocytes, the nuclear localization of myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte hypertrophy via myomesin-1-mediated sarcomere organization

A systematic review of population health interventions and Scheduled Tribes in India

<p>Abstract</p> <p>Background</p> <p>Despite India's recent economic growth, health and human development indicators of Scheduled Tribes (ST) or <it>Adivasi </it>(India's indigenous populations) lag behind national averages. The aim of this review was to identify the public health interventions or components of these interventions that are effective in reducing morbidity or mortality rates and reducing risks of ill health among ST populations in India, in order to inform policy and to identify important research gaps.</p> <p>Methods</p> <p>We systematically searched and assessed peer-reviewed literature on evaluations or intervention studies of a population health intervention undertaken with an ST population or in a tribal area, with a population health outcome(s), and involving primary data collection.</p> <p>Results</p> <p>The evidence compiled in this review revealed three issues that promote effective public health interventions with STs: (1) to develop and implement interventions that are low-cost, give rapid results and can be easily administered, (2): a multi-pronged approach, and (3): involve ST populations in the intervention.</p> <p>Conclusion</p> <p>While there is a growing body of knowledge on the health needs of STs, there is a paucity of data on how we can address these needs. We provide suggestions on how to undertake future population health intervention research with ST populations and offer priority research avenues that will help to address our knowledge gap in this area.</p

In Vitro Transformation of Primary Human CD34+ Cells by AML Fusion Oncogenes: Early Gene Expression Profiling Reveals Possible Drug Target in AML

Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of 4 major groups of AML fusion oncogenes on primary human CD34+ cells. As expected from their clinical similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They both caused erythroid hyperplasia and a clear block in erythroid and myeloid maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a dramatic increase in long-term proliferation and self-renewal. Gene expression profiling revealed two distinct temporal patterns of gene deregulation. Gene deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA occurred within 6 hours, followed by a dramatic drop in the numbers of deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1-ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53, specifically inhibited the proliferation and self-renewal of primary human CD34+ cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in cell transformation by AML1-ETO. These data show that differences among AML fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells and that early gene expression profiling in these cells can reveal potential drug targets in AML

Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome

Prediction of LDL cholesterol response to statin using transcriptomic and genetic variation

BACKGROUND: Statins are widely prescribed for lowering LDL-cholesterol (LDLC) levels and risk of cardiovascular disease. There is, however, substantial inter-individual variation in the magnitude of statin-induced LDLC reduction. To date, analysis of individual DNA sequence variants has explained only a small proportion of this variability. The present study was aimed at assessing whether transcriptomic analyses could be used to identify additional genetic contributions to inter-individual differences in statin efficacy. RESULTS: Using expression array data from immortalized lymphoblastoid cell lines derived from 372 participants of the Cholesterol and Pharmacogenetics clinical trial, we identify 100 signature genes differentiating high versus low statin responders. A radial-basis support vector machine prediction model of these signature genes explains 12.3% of the variance in statin-mediated LDLC change. Addition of SNPs either associated with expression levels of the signature genes (eQTLs) or previously reported to be associated with statin response in genome-wide association studies results in a combined model that predicts 15.0% of the variance. Notably, a model of the signature gene associated eQTLs alone explains up to 17.2% of the variance in the tails of a separate subset of the Cholesterol and Pharmacogenetics population. Furthermore, using a support vector machine classification model, we classify the most extreme 15% of high and low responders with high accuracy. CONCLUSIONS: These results demonstrate that transcriptomic information can explain a substantial proportion of the variance in LDLC response to statin treatment, and suggest that this may provide a framework for identifying novel pathways that influence cholesterol metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0460-9) contains supplementary material, which is available to authorized users

Angle tunable trapped mode in a THz metamaterial

We report trapped mode in Fano-like resonance in a terahertz (THz) metameterial (MM) consisting of a concentric circular and elliptical gold rings on semi-insulating GaAs substrate. We present the finite element method (FEM) based design, electron beam lithography based fabrication and 0.2-2 THz window spectroscopic results. The trapped mode of the MM can be tuned by the angle between the major axis of the ellipse and the polarization of incident THz electric field (maximum amplitude similar to 100V/m)

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Not AvailableCotton lint samples drawn from densely packed bales are required to be well opened and cleaned before being used for fibre quality assessment using modern testing equipment. Importance of proper opening of lint samples introduced into the porosity chamber for measurement of fibre fineness (micronaire) is well recognised to ensure not only correct micronaire but also strength values. If lint samples are tested as such without any opening and cleaning, there is every possibility of variations in the micronaire reading from the actual value. In this paper, performance of the two equipments namely trash analyzer and opener blender has been analysed for opening of cotton lint samples to ensure accurate and precise measurement of fibre fineness using High Volume Instrument. It was observed that while both equipments gave similar quality of opening, the capacity of trash analyser was nearly double due to its larger size when compared to opener blender.Not Availabl