Treatment of Obese Female and Male SHHF/Mcc-facp Rats with Antihypertensive Drugs,Nifedipine and Enalapril: Effects on Body Weight,Fat Distribution,Insulin Resistance and Systolic Pressure

Little is known about the effects of common antihypertensive drugs in obese, insulin-resistant females. Nine-month-old obese female SHHF/Mcc-fn^cp rats that received either nifedipine, a calcium channel antagonist, or enalapril, an angiotensin-converting-enzyme inhibitor, for three months were compared with untreated SHHF/Mcc-fa^cp rats (controls). After one month, nifedipine significantly decreased body weight in obese females compared to either enalapril or controls. After three months of treatment, total, abdominal, and subcutaneous fat masses were decreased in obese females given nifedipine compared to either enalapril or controls. Enalapril treatment was associated with a redistribution of fat mass from abdominal to subcutaneous depots. Nifedipine reduced plasma triglyceride and fasting glucose levels and improved insulin response to an oral glucose load in obese females, whereas enalapril did not appear to affect glycemic control. Systolic pressure was not significantly decreased until after two months of treatment with nifedipine or three months of treatment with enalapril in obese females and may have coincided with improvement in insulin-resistance. Similarly, plasma atrial natriuretic peptide concentrations were significantly lower in obese females given nifedipine. To determine how obese males responded to a calcium channel antagonist, six-month-old obese male SHHF/Mcc-fa^cp rats were treated for three months with either nifedipine or placebo (controls). Nifedipine-treated obese males showed a mild but significant decrease in weight gain that was due to a decrease in fat deposition in both subcutaneous and abdominal depots and systolic blood pressure was significantly reduced after one month of treatment. Nifedipine did not affect other plasma biochemical parameters in obese males. In conclusion, nifedipine improved systolic pressure and glycemic control in obese female SHHI;/Mcc-fa^cp rats, effects that may be associated with a marked loss in body weight and fat mass and improved lipid metabolism. Nifedipine-treated obese males exhibited only a diminished weight gain that was not associated with changes in diabetic characteristics.     

Murine norovirus protein NS1/2 aspartate to glutamate mutation,sufficient for persistence,reorients side chain of surface exposed tryptophan within a novel structured domain

Compact viral genomes such as those found in noroviruses, which cause significant enteric disease in humans, often encode only a few proteins, but affect a wide range of processes in their hosts and ensure efficient propagation of the virus. Both human and mouse noroviruses (MNVs) persistently replicate and are shed in stool, a highly effective strategy for spreading between hosts. For MNV, the presence of a glutamate rather than an aspartate at position 94 of the NS1/2 protein was previously shown to be essential for persistent replication and shedding. Here, we analyze these critical sequences of NS1/2 at the structural level. Using solution nuclear magnetic resonance methods, we determined folded NS1/2 domain structures from a nonpersistent murine norovirus strain CW3, a persistent strain CR6, and a persistent mutant strain CW3^D94E. We found an unstructured PEST‐like domain followed by a novel folded domain in the N‐terminus of NS1/2. All three forms of the domain are stable and monomeric in solution. Residue 94, critical for determining persistence, is located in a reverse turn following an α‐helix in the folded domain. The longer side chain of glutamate, but not aspartate, allows interaction with the indole group of the nearby tryptophan, reshaping the surface of the domain. The discrimination between glutamyl and aspartyl residue is imposed by the stable tertiary conformation. These structural requirements correlate with the in vivo function of NS1/2 in persistence, a key element of norovirus biology and infection. Proteins 2014; 82:1200–1209. © 2013 Wiley Periodicals, Inc.     

Improved estimates of incident radiation and heat load using non‐ parametric regression against topographic variables

Question: Can non‐parametric multiplicative regression (NPMR) improve estimates of potential direct incident radiation (PDIR) and heat load based on topographic variables, as compared to least‐squares multiple regression against trigonometric transforms of the predictors? Methods: We used a multiplicative kernel smoothing technique to interpolate between tabulated values of PDIR, using a locally linear model and a Gaussian kernel, with slope, aspect, and latitude as predictors. Heat load was calculated as a 45 degree rotation of the PDIR response surface. Results: This method yielded a fit to a complex response surface with R² > 0.99 and eliminated the areas of poor fit given by a previously published method based on least squares multiple regression with trigonometric functions of the predictors. Conclusions: Improved estimates of PDIR and heat load based on topographic variables can be obtained by using non‐parametric multiplicative regression (NPMR). The main drawback to the method is that it requires reference to the data tables, since those data are part of the model.