Solid-state NMR spectroscopic studies on the interaction of sorbic acid with phospholipid membranes at different pH levels.

2H, 31P, and 1H-magic-angle-spinning (MAS) solid-state NMR spectroscopic methods were used to elucidate the interaction between sorbic acid, a widely used weak acid food preservative, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers under both acidic and neutral pH conditions. The linewidth broadening observed in the 31P NMR powder pattern spectra and the changes in the 31P longitudinal relaxation time (T1) indicate interaction with the phospholipid headgroup upon titration of sorbic acid or decanoic acid into DMPC bilayers over the pH range from 3.0 to 7.

Anti-LOX-1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations.

LOX-1 is a multifunctional membrane receptor that binds and internalizes oxidized LDL (oxLDL). We tested the hypothesis that blockade of LOX-1 with an anti-LOX-1 antibody limits nephropathy in male rats with diabetes and dyslipidemia (ZS rats; F(1) hybrid product of Zucker fatty diabetic rats and spontaneous hypertensive heart failure rats). Lean ZS rats were controls, while untreated obese ZS (OM), ZS obese rats injected with nonspecific rabbit IgG (OM-IgG; 2 microg intravenous injection given weekly), and obese ZS rats given anti-LOX-1 rabbit antibody (OM-Ab; 2 microg intravenous injection given weekly) were the experimental groups.

Peroxisomal metabolism of propionic acid and isobutyric acid in plants.

The subcellular sites of branched-chain amino acid metabolism in plants have been controversial, particularly with respect to valine catabolism. Potential enzymes for some steps in the valine catabolic pathway are clearly present in both mitochondria and peroxisomes, but the metabolic functions of these isoforms are not clear. The present study examined the possible function of these enzymes in metabolism of isobutyryl-CoA and propionyl-CoA, intermediates in the metabolism of valine and of odd-chain and branched-chain fatty acids.

Functional comparison of citrate synthase isoforms from S. cerevisiae.

In this study, the product of the CIT3 gene has been identified as a dual specificity mitochondrial citrate and methylcitrate synthase and that of the CIT1 gene as a specific citrate synthase. Recombinant Cit1p had catalytic activity only with acetyl-CoA whereas Cit3p had similar catalytic efficiency with both acetyl-CoA and propionyl-CoA. Deletion of CIT1 dramatically shifted the ratio of these two activities in whole cell extracts towards greater methylcitrate synthase.

Evaluation of methods for sequence analysis of highly repetitive DNA templates.

The DNA Sequencing Research Group (DSRG) of the ABRF conducted a study to assess the ability of DNA sequencing core facilities to successfully sequence a set of well-defined templates containing difficult repeats. The aim of this study was to determine whether repetitive templates could be sequenced accurately by using equipment and chemistries currently utilized in participating sequencing laboratories. The effects of primer and template concentrations, sequencing chemistries, additives, and instrument formats on the ability to successfully sequence repeat elements were examined.

Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer.

Purpose: These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vivo and, if so, how.

Experimental Design: Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)-positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation were studied.

Drug watch. Pipeline progress: then and now.

The antiretroviral drug pipeline was last reviewed in BETA three years ago (see "The HIV/AIDS drug pipeline: a status report" in the Summer/Autumn 2002 issue). That report called on pharmaceutical companies to "ensure a steadier stream of innovative and affordable approaches to managing HIV infection." Is this goal being achieved?

The pipeline: three to watch.

Four antiretroviral drugs were approved in 2003: emtricitabine (FTC, Emtriva), and nucleoside reverse transcriptase inhibitor (NRTI); the protease inhibitors (PIs) atazanavir (Reyataz) and fosamprenavir (Lexiva); and T-20 (enfuvirtide, Fuzeon), the first of a new anti-HIV drug class, entry inhibitors.

Calpain regulates enterocyte brush border actin assembly and pathogenic Escherichia coli-mediated effacement.

This study identifies calpain as being instrumental for brush border (BB) microvillus assembly during differentiation and effacement during bacterial pathogenesis. Calpain activity is decreased by 25-80% in Caco 2 lines stably overexpressing calpastatin, the physiological inhibitor of calpain, and the effect is proportional to the calpastatin/calpain ratio. These lines exhibit a 2.

Profiling of differentially expressed apoptosis-related genes by cDNA arrays in human cord blood CD34+ cells treated with etoposide.

Objective: Understanding the molecular events that contribute to survival of and drug-induced apoptosis in hematopoietic stem and progenitor cells (HSC/P) can have impact on more rational approaches to blood cancer therapeutic design, as well as on strategies to minimize toxic side effects of chemotherapeutic drugs. Here we sought to systematically evaluate the basic molecular components and main pathways that govern and mediate cellular response initiated within human CD34(+) cells to etoposide-induced apoptosis.

Materials And Methods: Human CD34(+) cells were isolated from umbilical cord blood (CB) and expanded in vitro.

Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes.

Long-lasting tumor immunity requires functional mobilization of CD8+ and CD4+ T lymphocytes. CD4+ T cell activation is enhanced by presentation of shed tumor antigens by professional antigen-presenting cells (APCs), coupled with display of similar antigenic epitopes by major histocompatibility complex class II on malignant cells. APCs readily processed and presented several self-antigens, yet T cell responses to these proteins were absent or reduced in the context of class II+ melanomas.