347 research outputs found
Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture: direct action of thyroid hormone in vitro.
We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate
Excited-state Forces within a First-principles Green's Function Formalism
We present a new first-principles formalism for calculating forces for
optically excited electronic states using the interacting Green's function
approach with the GW-Bethe Salpeter Equation method. This advance allows for
efficient computation of gradients of the excited-state Born-Oppenheimer
energy, allowing for the study of relaxation, molecular dynamics, and
photoluminescence of excited states. The approach is tested on photoexcited
carbon dioxide and ammonia molecules, and the calculations accurately describe
the excitation energies and photoinduced structural deformations.Comment: 2 figures and 2 table
A First-Principles Study of the Electronic Reconstructions of LaAlO3/SrTiO3 Heterointerfaces and Their Variants
We present a first-principles study of the electronic structures and
properties of ideal (atomically sharp) LaAlO3/SrTiO3 (001) heterointerfaces and
their variants such as a new class of quantum well systems. We demonstrate the
insulating-to-metallic transition as a function of the LaAlO3 film thickness in
these systems. After the phase transition, we find that conduction electrons
are bound to the n-type interface while holes diffuse away from the p-type
interface, and we explain this asymmetry in terms of a large hopping matrix
element that is unique to the n-type interface. We build a tight-binding model
based on these hopping matrix elements to illustrate how the conduction
electron gas is bound to the n-type interface. Based on the `polar catastrophe'
mechanism, we propose a new class of quantum wells at which we can manually
control the spatial extent of the conduction electron gas. In addition, we
develop a continuous model to unify the LaAlO3/SrTiO3 interfaces and quantum
wells and predict the thickness dependence of sheet carrier densities of these
systems. Finally, we study the external field effect on both LaAlO3/SrTiO3
interfaces and quantum well systems. Our systematic study of the electronic
reconstruction of LaAlO3/SrTiO3 interfaces may serve as a guide to engineering
transition metal oxide heterointerfaces.Comment: 50 pages, 18 figures and 4 table
Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions
Key contributions to protein structure and stability are provided by weakly polar interactions, which arise from asymmetric electronic distributions within amino acids and peptide bonds. Of particular interest are aromatic side chains whose directional π-systems commonly stabilize protein interiors and interfaces. Here, we consider aromatic-aromatic interactions within a model protein assembly: the dimer interface of insulin. Semi-classical simulations of aromatic-aromatic interactions at this interface suggested that substitution of residue TyrB26 by Trp would preserve native structure while enhancing dimerization (and hence hexamer stability). The crystal structure of a [TrpB26]insulin analog (determined as a T3Rf3 zinc hexamer at a resolution of 2.25 Å) was observed to be essentially identical to that of WT insulin. Remarkably and yet in general accordance with theoretical expectations, spectroscopic studies demonstrated a 150-fold increase in the in vitro lifetime of the variant hexamer, a critical pharmacokinetic parameter influencing design of long-acting formulations. Functional studies in diabetic rats indeed revealed prolonged action following subcutaneous injection. The potency of the TrpB26-modified analog was equal to or greater than an unmodified control. Thus, exploiting a general quantum-chemical feature of protein structure and stability, our results exemplify a mechanism-based approach to the optimization of a therapeutic protein assembly
Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels
Resonant phonon coupling across the La{1-x}Sr{x}MnO{3}/SrTiO{3} interface
The transport and magnetic properties of correlated La{0.53}Sr{0.47}MnO{3}
ultrathin films, grown epitaxially on SrTiO{3}, show a sharp cusp at the
structural transition temperature of the substrate. Using a combination of
experiment and theory we show that the cusp is a result of resonant coupling
between the charge carriers in the film and a soft phonon mode in the SrTiO{3},
mediated through oxygen octahedra in the film. The amplitude of the mode
diverges towards the transition temperature, and phonons are launched into the
first few atomic layers of the film affecting its electronic state
Effect of Semicore Orbitals on the Electronic Band Gaps of Si, Ge, and GaAs within the GW Approximation
We study the effect of semicore states on the self-energy corrections and
electronic energy gaps of silicon, germanium and GaAs. Self-energy effects are
computed within the GW approach, and electronic states are expanded in a
plane-wave basis. For these materials, we generate {\it ab initio}
pseudopotentials treating as valence states the outermost two shells of atomic
orbitals, rather than only the outermost valence shell as in traditional
pseudopotential calculations. The resulting direct and indirect energy gaps are
compared with experimental measurements and with previous calculations based on
pseudopotential and ``all-electron'' approaches. Our results show that,
contrary to recent claims, self-energy effects due to semicore states on the
band gaps can be well accounted for in the standard valence-only
pseudopotential formalism.Comment: 6 pages, 3 figures, submitted to Phys. Rev.
Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes
Background and objectives In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. Design, setting, participants, & measurements The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. Results There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). Conclusions In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events
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