1,424 research outputs found
Wetting to Non-wetting Transition in Sodium-Coated C_60
Based on ab initi and density-functional theory calculations, an empirical
potential is proposed to model the interaction between a fullerene molecule and
many sodium atoms. This model predicts homogeneous coverage of C_60 below 8 Na
atoms, and a progressive droplet formation above this size. The effects of
ionization, temperature, and external electric field indicate that the various,
and apparently contradictory, experimental results can indeed be put into
agreement.Comment: 4 pages, 4 postscript figure
Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1α : modulation by p38 MAPK
The transcriptional coactivator PPAR gamma coactivator 1 α (PGC-1α) is a key regulator of metabolic processes such as mitochondrial biogenesis and respiration in muscle and gluconeogenesis in liver. Reduced levels of PGC-1α in humans have been associated with type II diabetes. PGC-1α contains a negative regulatory domain that attenuates its transcriptional activity. This negative regulation is removed by phosphorylation of PGC-1α by p38 MAPK, an important kinase downstream of cytokine signaling in muscle and ÎČ-adrenergic signaling in brown fat. We describe here the identification of p160 myb binding protein (p160MBP) as a repressor of PGC-1α. The binding and repression of PGC-1α by p160MBP is disrupted by p38 MAPK phosphorylation of PGC-1α. Adenoviral expression of p160MBP in myoblasts strongly reduces PGC-1α's ability to stimulate mitochondrial respiration and the expression of the genes of the electron transport system. This repression does not require removal of PGC-1α from chromatin, suggesting that p160MBP is or recruits a direct transcriptional suppressor. Overall, these data indicate that p160MBP is a powerful negative regulator of PGC-1α function and provide a molecular mechanism for the activation of PGC-1α by p38 MAPK. The discovery of p160MBP as a PGC-1α regulator has important implications for the understanding of energy balance and diabetes
Exchange Monte Carlo for Molecular Simulations with Monoelectronic Hamiltonians
We introduce a general Monte Carlo scheme for achieving atomistic simulations
with monoelectronic Hamiltonians including the thermalization of both nuclear
and electronic degrees of freedom. The kinetic Monte Carlo algorithm is used to
obtain the exact occupation numbers of the electronic levels at canonical
equilibrium, and comparison is made with Fermi-Dirac statistics in infinite and
finite systems. The effects of a nonzero electronic temperature on the
thermodynamic properties of liquid silver and sodium clusters are presented
Combined impact of lifestyle factors on mortality: prospective cohort study in US women
Objective To evaluate the impact of combinations of lifestyle factors on mortality in middle aged women
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Toenail Selenium and Incidence of Type 2 Diabetes in U.S. Men and Women
OBJECTIVE Compelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM. RESEARCH DESIGN AND METHODS We performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982â1983 and 1986â1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards. RESULTS During 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73â1.14), 0.78 (0.62â0.99), 0.72 (0.57â0.91), and 0.76 (0.60â0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear. CONCLUSIONS At dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk
Home Endotoxin Exposure and Wheeze in Infants: Correction for Bias Due to Exposure Measurement Error
Exposure to elevated levels of endotoxin in family-room dust was previously observed to be significantly associated with increased wheeze in the first year of life among a cohort of 404 children in the Boston, Massachusetts, metropolitan area. However, it is likely that family-room dust endotoxin was a surrogate for airborne endotoxin exposure. Therefore, a related substudy characterized the relationship between levels of airborne household endotoxin and the level of endotoxin present in house dust, in addition to identifying other significant predictors of airborne endotoxin in the home. We now reexamine the relationship between endotoxin exposure and wheeze under the assumption that the level of airborne endotoxin in the home is the exposure of interest and that the amount of endotoxin in household dust is a surrogate for this exposure. We applied a measurement error correction technique, using all available data to estimate the effect of endotoxin exposure in terms of airborne concentration and accounting for the measurement error induced by using house-dust endotoxin as a surrogate measure in the portion of the data in which airborne endotoxin could not be directly measured. After adjusting for confounding by lower respiratory infection status and race/ethnicity, endotoxin exposure was found to be significantly associated with a nearly 6-fold increase in prevalence of wheeze for a one interquartile range increase in airborne endotoxin (95% confidence interval, 1.2â26) among the 360 children in households with dust endotoxin levels between the 5th and 95th percentiles
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Circulating Omegaâ3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study
Background: Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omegaâ3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results: In the communityâbased Cardiovascular Health Study, 3660 participants aged â„65 underwent brain MRI in 1992â1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992â1993 and related to crossâsectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest longâchain omegaâ3 PUFA quartile. Higher longâchain omegaâ3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediateâchain omegaâ3 PUFA alphaâlinolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alphaâlinolenic acid intake. Conclusions: Among older adults, higher phospholipid longâchain omegaâ3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of longâchain omegaâ3 PUFAs, on brain health in later life. The role of plantâderived alphaâlinolenic acid in brain health requires further investigation
Partnership of PGC-1α and HNF4α in the regulation of lipoprotein metabolism
Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator involved in several aspects of energy metabolism. It is induced or activated under different stimuli in a highly tissue-specific manner and subsequently partners with certain transcription factors in those tissues to execute various biological programs. In the fasted liver, PGC-1α is induced and interacts with hepatocyte nuclear factor 4α (HNF4α) and other transcription factors to activate gluconeogenesis and increase hepatic glucose output. Given the broad spectrum of liver genes responsive to HNF4α, we sought to determine those that were specifically targeted by the combination of PGC-1α and HNF4α. Coexpression of these two molecules in murine stem cells reveals a high induction of mRNA for apolipoproteins A-IV and C-II. Forced expression of PGC-1α in mouse and human hepatoma cells increases the mRNA of a subset of apolipoproteins implicated in very low density lipoprotein and triglyceride metabolism, including apolipoproteins A-IV, C-II, and C-III. Coactivation of the apoC-III/A-IV promoter region by PGC-1α occurs through a highly conserved HNF4α response element, the loss of which completely abolishes activation by PGC-1α and HNF4α. Adenoviral infusion of PGC-1α into live mice increases hepatic expression of apolipoproteins A-IV, C-II, and C-III and increases serum and very low density lipoprotein triglyceride levels. Conversely, knock down of PGC-1α in vivo causes a decrease in both apolipoprotein expression and serum triglyceride levels. These data point to a crucial role for the PGC-1α/HNF4α partnership in hepatic lipoprotein metabolism
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