Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids.

Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources into a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants.

The Iterative Protein Redesign and Optimization (IPRO) suite of programs.

Proteins are an important class of biomolecules with applications spanning across biotechnology and medicine. In many cases, native proteins must be redesigned to improve various performance metrics by changing their amino acid sequences. Algorithms can help sharpen protein library design by focusing the library on sequences that optimize computationally accessible proxies.

A framework to integrate habitat monitoring and restoration with endangered insect recovery.

Monitoring is essential to track the long-term recovery of endangered species. Greater emphasis on habitat monitoring is especially important for taxa whose populations may be difficult to quantify (e.g.

OptZyme: computational enzyme redesign using transition state analogues.

OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate.

Essential role of p38 MAPK for activation of skeletal muscle glucose transport by lithium.

Lithium increases glucose transport and glycogen synthesis in insulin-sensitive cell lines and rat skeletal muscle, and has been used as a non-selective inhibitor of glycogen synthase kinase-3 (GSK-3). However, the molecular mechanisms underlying lithium action on glucose transport in mammalian skeletal muscle are unknown. Therefore, we examined the effects of lithium on glucose transport activity, glycogen synthesis, insulin signaling elements (insulin receptor (IR), Akt, and GSK-3beta), and the stress-activated p38 mitogen-activated protein kinase (p38 MAPK) in the absence or presence of insulin in isolated soleus muscle from lean Zucker rats.

A role for the unfolded protein response in optimizing antibody secretion.

Terminal differentiation of B lymphocytes into antibody(Ab)-secreting plasma cells is marked by a sharp rise in immunoglobulin (Ig) biosynthesis that increases demand on the protein folding capacity of the endoplasmic reticulum (ER). The unfolded protein response pathway (UPR) allows cells to respond to challenging conditions within the ER, in part by the activities of the XBP1 and ATF6alpha/beta transcription factors. The UPR is activated in differentiating B cells, and XBP1 is required for the generation of Ab-secreting plasma cells.

Microbiology of severe aspiration pneumonia in institutionalized elderly.

We sought to investigate prospectively the microbial etiology and prognostic indicators of 95 institutionalized elders with severe aspiration pneumonia, and to investigate its relation to oral hygiene in using quantitative bronchial sampling. Data collection included demographic information, Activity of Daily Living, Plaque Index, antimicrobial therapy, and outcome. Out of the 67 pathogens identified, Gram-negative enteric bacilli were the predominant organisms isolated (49%), followed by anaerobic bacteria (16%), and Staphylococcus aureus (12%).

Activation of an unfolded protein response during differentiation of antibody-secreting B cells.

The unfolded protein response pathway (UPR) is believed to detect and compensate for excessive protein accumulation in the endoplasmic reticulum (ER). The UPR can be induced by pharmacological agents that perturb ER functions, but may also occur during cellular developmental processes such as the transition of B-lymphocytes into antibody-secreting plasma cells. Here we show that major UPR components are activated in B cells stimulated to secrete antibody.

Russian immigrant cardiovascular risk assessment.

Immigration from the former Soviet Union has been increasing. In 1990, there were 454,000 Russian immigrants living in the United States. Lifestyle habits prevalent in Russia, including smoking, alcoholism, and little preventive health, are compelling medical and economic reasons to understand the health status of this population.

Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes.

Objective: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy.

The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.

Background: It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study.

Methods: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes.