Viral self-assembly as a thermodynamic process

The protein shells, or capsids, of all sphere-like viruses adopt icosahedral symmetry. In the present paper we propose a statistical thermodynamic model for viral self-assembly. We find that icosahedral symmetry is not expected for viral capsids constructed from structurally identical protein subunits and that this symmetry requires (at least) two internal "switching" configurations of the protein. Our results indicate that icosahedral symmetry is not a generic consequence of free energy minimization but requires optimization of internal structural parameters of the capsid proteins.Comment: pdf file, 13 pages, three figure

Elucidating the Metabolic Regulation of Liver Regeneration

The regenerative capability of liver is well known, and the mechanisms that regulate liver regeneration are extensively studied. Such analyses have defined general principles that govern the hepatic regenerative response and implicated specific extracellular and intracellular signals as regulated during and essential for normal liver regeneration. Nevertheless, the most proximal events that stimulate liver regeneration and the distal signals that terminate this process remain incompletely understood. Recent data suggest that the metabolic response to hepatic insufficiency might be the proximal signal that initiates regenerative hepatocellular proliferation. This review provides an overview of the data in support of a metabolic model of liver regeneration and reflects on the clinical implications and areas for further study suggested by these findings

Functional Relationships between Lipid Metabolism and Liver Regeneration

The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research

Seasonal lags between organic carbon deposition and mineralization in marine sediments

The fate of phytoplankton detritus in the muddy sediments of shallow marine ecosystems was studied by labelling the water column of a 13 m3 microcosm with radiocarbon bicarbonate from January to July. By the end of the study, more than 9% of the original inorganic label was found as organic carbon in the top 10 cm of sediment. The accumulation of labelled organic carbon in the sediment totalled 14.5 gC/m2. We estimate that this amount represented 15% of daytime net primary production and roughly half of the labelled organic carbon that was deposited on the sediment. The finding of sedimentary carbon accumulation directly demonstrated that time lags on the order of months can exist between the deposition and mineralization of phytoplankton detritus in nature. Observed time lags may have occurred because heterotrophic activity was minimize by low winter and spring temperatures, pelagic and benthic grazing was minimal, and bioturbation rates were high. Mineralization of organic carbon may have been retarded by conditions in subsurface sediments. Detritus buried in the sediment during the winter and spring would have been available to the subsurface feeding benthos during the summer, when maximum metabolic demand occurs

Light Attenuation in Estuarine Mangrove Lakes

Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (\u3c2 m depth) mangrove-surrounded lakes in two sub-estuaries in the coastal Everglades, Florida USA. Turbidity, chromophoric dissolved organic matter (CDOM), and phytoplankton chlorophyll a (chl a) were measured concurrently and their respective contributions to the light attenuation rate were estimated. Light transmission to the benthos relative to literature estimates of minimum requirements for SAV growth indicated that the underwater light environment was often unsuitable for SAV. Light attenuation rates (n = 417) corrected for solar elevation angles ranged from 0.16 m-1 to 9.83 m-1 with a mean of 1.73 m-1. High concentrations of CDOM with high specific light absorption contributed the most to light attenuation followed by turbidity and chl a. CDOM alone sufficiently reduces light transmission beyond the estimated limits for SAV growth, making it difficult for ecosystem managers to increase SAV abundance by management activities. Light limitation of SAV in these areas may be a persistent feature because of their proximity to CDOM source materials from the surrounding mangrove swamp. Increasing freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities

The effective potential, critical point scaling and the renormalization group

The desirability of evaluating the effective potential in field theories near a phase transition has been recognized in a number of different areas. We show that recent Monte Carlo simulations for the probability distribution for the order parameter in an equilibrium Ising system, when combined with low-order renormalization group results for an ordinary $\phi^4$ system, can be used to extract the effective potential. All scaling features are included in the process.Comment: REVTEX file, 22 pages, three figures, submitted to Phys. Rev.

Diet modifies pioglitazone’s influence on hepatic PPARγ-regulated mitochondrial gene expression

Pioglitazone (Pio) is a thiazolidinedione (TZD) insulin-sensitizing drug whose effects result predominantly from its modulation of the transcriptional activity of peroxisome proliferator-activated-receptor-gamma (PPARγ). Pio is used to treat human insulin-resistant diabetes and also frequently considered for treatment of nonalcoholic steatohepatitis (NASH). In both settings, Pio’s beneficial effects are believed to result primarily from its actions on adipose PPARγ activity, which improves insulin sensitivity and reduces the delivery of fatty acids to the liver. Nevertheless, a recent clinical trial showed variable efficacy of Pio in human NASH. Hepatocytes also express PPARγ, and such expression increases with insulin resistance and in nonalcoholic fatty liver disease (NAFLD). Furthermore, mice that overexpress hepatocellular PPARγ and Pio-treated mice with extrahepatic PPARγ gene disruption develop features of NAFLD. Thus, Pio’s direct impact on hepatocellular gene expression might also be a determinant of this drug’s ultimate influence on insulin resistance and NAFLD. Previous studies have characterized Pio’s PPARγ-dependent effects on hepatic expression of specific adipogenic, lipogenic, and other metabolic genes. However, such transcriptional regulation has not been comprehensively assessed. The studies reported here address that consideration by genome-wide comparisons of Pio’s hepatic transcriptional effects in wildtype (WT) and liver-specific PPARγ-knockout (KO) mice given either control or high-fat (HFD) diets. The results identify a large set of hepatic genes for which Pio’s liver PPARγ-dependent transcriptional effects are concordant with its effects on RXR-DNA binding in WT mice. These data also show that HFD modifies Pio’s influence on a subset of such transcriptional regulation. Finally, our findings reveal a broader influence of Pio on PPARγ-dependent hepatic expression of nuclear genes encoding mitochondrial proteins than previously recognized. Taken together, these studies provide new insights about the tissue-specific mechanisms by which Pio affects hepatic gene expression and the broad scope of this drug’s influence on such regulation