S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass spectrometry identified the active derivative of MMP-9, both in vitro and in vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S-nitrosylation. These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity.     

A heat-sensitive TRP channel expressed in keratinocytes

Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.     

Developing sustainable agriculture education in Canada

In a number of surveys, Canadian farmers have found the absence of information to be a major obstacle to the development of sustainable agriculture. The traditional sources of information for farmers have been unable to provide them with suitable information. One reason for this deficiency is the absence of suitable training for agriculture professionals. The details of a newly created course designed to address these problems at the Faculty of Agriculture of McGill University are provided, and some suggestions made about the pedagogy and course content of an entire program.     

Colloid osmotic pressure after hemorrhage and replenishment with Oxyglobin Solution, hetastarch, or whole blood in pregnant sheep

Objective To compare plasma colloid osmotic pressure (COP) of both maternal and fetal blood, before and after hemorrhage, and replenishment with Oxyglobin Solution (Biopure Corporation, Cambridge, MA, USA), hetastarch or whole blood in pregnant ewes. Study design Prospective, randomized study. Animals A total of 17 adult Rambouillet ewes at 131 (128–133) [median (minimum, maximum)] days gestation, weighing 56 (46, 63) kg. Methods Ewes and fetuses were chronically instrumented with catheters in a maternal jugular vein, maternal carotid artery and fetal femoral artery. Twenty milliliters per kilograms of blood were removed from each ewe over 1 hour. The ewes were then given 20 mL kg^?1 of either Oxyglobin Solution (n = 5), hetastarch (n = 6), or autologous whole blood (n = 6) IV. Maternal plasma COP was measured before hemorrhage, after hemorrhage, after replenishment, and 1 and 2 hours later. Fetal plasma COP was measured after maternal hemorrhage and 2 hours after maternal volume replenishment. Results Median COP of all ewes before hemorrhage was 20 (16, 24) mm Hg and after hemorrhage (p < 0.05), decreased to 16 (11, 19) mm Hg. After volume replenishment, the COP of the Oxyglobin Solution group was 22 (21, 25) mm Hg, the autologous whole blood group was 17 (16, 22) mm Hg and the hetastarch group was 20 (17, 21) mm Hg. The COP of the Oxyglobin Solution group was significantly greater (p < 0.05) than the COP of the hetastarch group immediately and 60 minutes after volume replenishment, and greater (p < 0.05) than that of the autologous whole blood group at 60 minutes after volume replenishment. The COP of all the fetuses after maternal hemorrhage was 16 (12, 19) mm Hg and at 120 minutes after maternal volume replenishment was 15 (11, 18) mm Hg. There were no differences in COP between or within any of the fetal groups. Conclusions When used to treat blood loss, Oxyglobin Solution increases plasma COP more than an equal volume of hetastarch in the first hour following administration. Maternal administration of Oxyglobin Solution did not alter fetal COP. Clinical relevance Oxyglobin Solution is a more potent colloid than hetastarch. Oxyglobin Solution did not appear to translocate fluid from the fetal to maternal circulation.     

Impact of nutrients on insulin-like growth factor-I, insulin-like growth factor binding protein-3 and their ratio in African American and white males

OBJECTIVE: Higher levels of insulin-like growth factor-I (IGF-I) and lower levels of IGF binding protein-3 (IGFBP-3) have been associated with an increased risk of prostate cancer. Nutrition is known to partially regulate IGF levels and it is possible that nutritional factors mediate the impact of IGF levels on prostate cancer risk. Design: A cross-sectional analysis of the impact of nutritional factors measured by a dietary questionnaire on plasma levels of IGF-I, IGFBP-3 and their molar ratio. Multiple linear regression analysis was used to test for effects of nutrients on IGF levels. SETTING: Prostate cancer screening at the Hollings Cancer Center in Charleston, South Carolina. SUBJECTS: Ninety-five African American and 138 white males aged 33-83 years attending the screening. RESULTS: In whites, intakes of total, saturated and monounsaturated fats were positively associated with an increase in the molar ratio, while there was no association in African Americans. In African Americans, we found that increasing intake of calcium and dairy servings was positively associated with IGF-I levels. Increased vegetable intake was positively associated with IGFBP-3 in African Americans, while there was no effect in whites. A higher percentage of alcohol in the total diet was significantly associated with a decrease in the molar ratio and an increase in IGFBP-3 in both groups. CONCLUSIONS: Our results confirm previous findings of nutritional determinants of IGF levels. Additionally, we found the impact of several nutrients on IGF levels to be different in whites and African Americans, which warrants further investigation.     

Effect of SO2 concentration on polyphenol development during red wine micro-oxygenation

A Merlot wine in 15 L research tanks was subjected to micro-oxygenation at 10 mL O2 per liter of wine per month over a 16 week period with additions of 0, 50, 100, and 200 mg/L SO2. A large decrease in monomeric anthocyanins and flavan-3-ols was seen in wines with a lower concentration of SO2, coupled with an increase in nonbleachable pigments; an increase in tannin, measured using precipitation with methyl cellulose; and a greater size and red coloration of a proanthocyanidin extract obtained using Sephadex LH-20. These changes were largely suppressed in wines initially treated with 200 mg/L SO2 and occurred more slowly in wines stored in bottles in the absence of O2. The concentration of SO2 is shown to regulate the polyphenol chemistry involved in the formation of polymeric pigments and changes in tannin structure affecting wine astringency.     

Effect of surimi processing on dimethylamine formation in fish meat during frozen storage

Trimethylamine-N-oxide (TMAO) degrades to dimethylamine (DMA) and formaldehyde, which cause a decline in fish quality. Suppression of DMA formation in frozen surimi was investigated using croaker, lizardfish, and walleye pollock. The leaching process in surimi processing was shown to reduce not only the TMAO, iron, and taurine content, but also to reduce unidentified factors that accelerate DMA formation in lizardfish muscle; in contrast, unidentified factors that suppress DMA formation were reduced in croaker and pollock muscle. Sucrose, used as a cryoprotectant, was shown to decrease DMA formation in vitro, likely due to the reduction in freezing-induced concentration of solutes. The effects of pH on DMA formation were different in minced frozen meat among the three species. DMA formation was not observed in croaker when the pH varied between 6 and 8. On the other hand, DMA was elevated in lizardfish under acidic conditions, and DMA formation in pollock was maximal when the pH of the meat was neutral. Thus, the suppression of TMAO degradation by surimi processing results from the removal of TMAO, iron, and reductants from fish meat; sucrose also reduces DMA formation. Furthermore, unidentified factors in croaker, lizardfish, and pollock meat substantially affect DMA formation.