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 β-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

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

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

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

Transition State Spectroscopy of the Photoinduced Ca + CH3F Reaction. 2. Experimental and Ab Initio Studies of the Free Ca***FCH3 Complex

International audienceThe Ca* + CH3F CaF* + CH3 reaction was photoinduced in 1:1 Ca***CH3F complexes formed in a supersonic expansion. The transition state of the reaction was explored by monitoring the electronically excited product, CaF, while scanning the laser that turns on the reaction. Moreover, the electronic structure of the Ca***FCH3 system was studied using ab initio methods by associating a pseudopotential description of the [Ca2+] and [F7+] cores, a core polarization operator on calcium, an extensive Gaussian basis and a treatment of the electronic problem at the CCSD(T) (ground state) and RSPT2 (excited states) level. In this contribution we present experimental results for the free complex and a comparison with the results of a previous experiment where the Ca***CH3F complexes are deposited at the surface of large argon clusters. The ab initio calculations allowed an interpretation of the experimental data in terms of two reaction mechanisms, one involving a partial charge transfer state, the other involving the excitation of the C-F stretch in the CH3F moiety prior to charge transfer

Degenerate dispersive equations arising in the study of magma dynamics

An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Models for this process, transport in a viscously deformable porous media, give rise to scalar degenerate, dispersive, nonlinear wave equations. We establish a general local well-posedness for a physical class of data (roughly $H^1$) via fixed point methods. The strategy requires positive lower bounds on the solution. This is extended to global existence for a subset of possible nonlinearities by making use of certain conservation laws associated with the equations. Furthermore, we construct a Lyapunov energy functional, which is locally convex about the uniform state, and prove (global in time) nonlinear dynamic stability of the uniform state for any choice of nonlinearity. We compare the dynamics to that of other problems and discuss open questions concerning a larger range of nonlinearities, for which we conjecture global existence.Comment: 27 Pages, 7 figures are not present in this version. See http://www.columbia.edu/~grs2103/ for a PDF with figures. Submitted to Nonlinearit

Whole Grain, Bran, and Germ Intake and Risk of Type 2 Diabetes: A Prospective Cohort Study and Systematic Review

Background: Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes, but the role of specific dietary factors in the etiology of type 2 diabetes is less well established. We evaluated intakes of whole grain, bran, and germ in relation to risk of type 2 diabetes in prospective cohort studies. Methods and Findings: We followed 161,737 US women of the Nurses' Health Studies (NHSs) I and II, without history of diabetes, cardiovascular disease, or cancer at baseline. The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up. Other prospective cohort studies on whole grain intake and risk of type 2 diabetes were identified in searches of MEDLINE and EMBASE up to January 2007, and data were independently extracted by two reviewers. The median whole grain intake in the lowest and highest quintile of intake was, respectively, 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII. After adjustment for potential confounders, the relative risks (RRs) for the highest as compared with the lowest quintile of whole grain intake was 0.63 (95% confidence interval [CI] 0.57–0.69) for NHSI and 0.68 (95% CI 0.57–0.81) for NHSII (both: p-value, test for trend <0.001). After further adjustment for body mass index (BMI), these RRs were 0.75 (95% CI 0.68–0.83; p-value, test for trend <0.001) and 0.86 (95% CI 0.72–1.02; p-value, test for trend 0.03) respectively. Associations for bran intake were similar to those for total whole grain intake, whereas no significant association was observed for germ intake after adjustment for bran. Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes, a two-serving-per-day increment in whole grain consumption was associated with a 21% (95% CI 13%–28%) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI. Conclusions: Whole grain intake is inversely associated with risk of type 2 diabetes, and this association is stronger for bran than for germ. Findings from prospective cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes

Associations of Plasma Phospholipid and Dietary Alpha Linolenic Acid With Incident Atrial Fibrillation in Older Adults: The Cardiovascular Health Study

Background: Few studies have examined the relationship of α‐linolenic acid (ALA 18:3n‐3), an intermediate‐chain essential n‐3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). Methods and Results: The study population included participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF

Consumption and acceptability of whole grain staples for lowering markers of diabetes risk among overweight and obese Tanzanian adults

Background: Dietary changes characterized by a reduction in carbohydrate quality are occurring in developing countries and may be associated with a higher prevalence of obesity and chronic diseases such as type 2 diabetes mellitus. We assessed the preferences and acceptability of unrefined whole grain carbohydrate staples (i.e., brown rice, unrefined maize and unrefined sorghum ugali) as substitutes for commonly consumed refined carbohydrates in Tanzania. Methods: A questionnaire was used to collect sociodemographic information and dietary habits, and pre-and post-tasting questionnaires were administered for test foods. A 10-point LIKERT scale was used to rate attributes of the three test foods. Results: White rice and refined maize ugali were the most commonly consumed carbohydrate staples in this population; 98% and 91%, respectively. Occasional consumption of unrefined maize and sorghum ugali was reported by 32% and 23% of the participants, respectively. All of the test foods were highly rated for smell, taste, color, appearance and texture. Taste was rated highest for unrefined maize ugali. Almost all of the participants were willing to participate in a future dietary intervention involving regular consumption of these unrefined carbohydrates for at least six months duration. Conclusions: These findings suggest that whole grain carbohydrates are highly acceptable, and that there is a promising potential for their use in future dietary intervention studies in Tanzania