Parallel evaluation of alternative skin barrier models and excised human skin for dermal absorption studies in vitro.

Skin permeation is a primary consideration in the safety assessment of cosmetic ingredients, topical drugs, and human users handling veterinary medicinal products. While excised human skin (EHS) remains the 'gold standard' for in vitro permeation testing (IVPT) studies, unreliable supply and high cost motivate the search for alternative skin barrier models. In this study, a standardized dermal absorption testing protocol was developed to evaluate the suitability of alternative skin barrier models to predict skin absorption in humans.

Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid.

Strategies to prevent diabetic microvascular angiopathy focus on the vascular endothelium. Because red blood cells (RBCs) are less deformable in diabetes, we explored an original concept linking decreased RBC deformability to RBC ascorbate and hyperglycemia. We characterized ascorbate concentrations from human and mouse RBCs and plasma, and showed an inverse relationship between RBC ascorbate concentrations and deformability, measured by osmotic fragility.

Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics.

Significance: Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. However, the route of administration results in major differences in ascorbate bioavailability.

Chromatographic purification of highly active yeast ribosomes.

Eukaryotic ribosomes are much more labile as compared to their eubacterial and archael counterparts, thus posing a significant challenge to researchers. Particularly troublesome is the fact that lysis of cells releases a large number of proteases and nucleases which can degrade ribosomes. Thus, it is important to separate ribosomes from these enzymes as quickly as possible.

High throughput structural analysis of yeast ribosomes using hSHAPE.

Global mapping of rRNA structure by traditional methods is prohibitive in terms of time, labor and expense. High throughput selective 2' hydroxyl acylation analyzed by primer extension (hSHAPE) bypasses these problems by using fluorescently labeled primers to perform primer extension reactions, the products of which can be separated by capillary electrophoresis, thus enabling long read lengths in a cost effective manner. The data so generated is analyzed in a quantitative fashion using SHAPEFinder.

Enhanced purity, activity and structural integrity of yeast ribosomes purified using a general chromatographic method.

One of the major challenges facing researchers working with eukaryotic ribosomes lies in their lability relative to their eubacterial and archael counterparts. In particular, lysis of cells and purification of eukaryotic ribosomes by conventional differential ultracentrifugation methods exposes them for long periods of time to a wide range of co-purifying proteases and nucleases, negatively impacting their structural integrity and functionality. A chromatographic method using a cysteine charged Sulfolink resin was adapted to address these problems.

Population-level variation of the preproricin gene contradicts expectation of neutral equilibrium for generalist plant defense toxins.

The preproricin gene encodes ricin, the highly toxic, type II ribosome-inactivating protein of castor bean (Ricinus communis L.). As a generalist plant defense gene, preproricin is expected to exhibit population-level variation consistent with the neutral equilibrium model and to comprise few functionally different alleles.

Characterization of ricin toxin family members from Ricinus communis.

Ricin inhibits translation by removal of a specific adenine from 28S RNA. The Ricinus communis genome encodes seven full-length ricin family members. All encoded proteins have the ability of hydrolyzing adenine in 28S rRNA.

Sequence specific detection of DNA using nicking endonuclease signal amplification (NESA).

We have developed a new method for identifying specific single- or double-stranded DNA sequences called nicking endonuclease signal amplification (NESA). A probe and target DNA anneal to create a restriction site that is recognized by a strand-specific endonuclease that cleaves the probe into two pieces leaving the target DNA intact. The target DNA can then act as a template for fresh probe and the process of hybridization, cleavage and dissociation repeats.