Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis

The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when overexpressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.     

Mechanisms involved in the regulation of histone lysine demethylases

Since the first histone lysine demethylase KDM1 (LSD1) was discovered in 2004, a great number of histone demethylases have been recognized and shown to play important roles in gene expression, as well as cellular differentiation and animal development. The chemical mechanisms and substrate specificities have already been extensively discussed elsewhere. This review focuses primarily on regulatory mechanisms that modulate demethylase recruitment and activity.     

Evaluation of AFLPs for germplasm fingerprinting and assessment of genetic diversity in cultivars of tomato (Lycopersicon esculentum L.).

Cultivated tomato (L. esculentum L.) germplasm exhibits limited genetic variation compared with wild Lycopersicon species. Amplified fragment length polymorphism (AFLP) markers were used to evaluate genetic variation among 74 cultivars, primarily from California, and to fingerprint germplasm to determine if cultivar-specific patterns could be obtained. All 74 cultivars were genotyped using 26 AFLP primer combinations; of the 1092 bands scored, 102 AFLP bands (9.3%) were polymorphic. Pair-wise genetic similarity coefficients (Jaccard and Nei-Li) were calculated. Jaccard coefficients varied from 0.16 to 0.98 among cultivar pairs, and 72% of pair-wise comparisons exceeded 0.5. UPGMA (unweighted pair-group method with arithmetic averaging) clustering and principle component analysis revealed four main clusters, I-IV; most modern hybrid cultivars grouped in II, whereas most vintage cultivars grouped in I. Clusters III and IV contained three and two cultivars, respectively. Some groups of cultivars closely related by pedigree exhibited high bootstrap values, but lower values (<50%) were obtained for cluster II and its four subgroups. Unique fingerprints for all 74 cultivars were obtained by a minimum of seven AFLP primer pairs, despite inclusion of some closely related cultivars. This study demonstrated that AFLP markers are effective for obtaining unique fingerprints of, and assessing genetic diversity among, tomato cultivars.     

Machinery Risk Assessment for Risk Reduction

New avenues are reviewed and discussed for preventing industrial machine-related injury by means of realistic risk evaluation and reduction processes at the design and application stages of machinery development and use. U.S. guidelines and European standards on machinery risk assessment procedures are described. Applications of risk assessment for machine-related injury risk management and teaching machine-risk control are discussed.     

Vincristine and vinblastine lower plasma cholesterol concentrations in rhesus monkeys

3-4 days after a single clinical dose of vincristine or vinblastine in rhesus monkeys there was a marked decrease in plasma low-density lipoprotein cholesterol concentrations. There was also a concomitant increase in plasma triacylglycerol concentrations. Plasma lipid levels returned to normal concentrations within 7-10 days after injection. Plasma high-density lipoprotein cholesterol concentrations were unaltered by the drugs. Electron micrographs of the hepatocytes from monkeys treated with vincristine or vinblastine showed an accumulation of glycogen particles and proliferation of smooth endoplasmic reticulum, which was accompanied by an increase in the number of lipoprotein-containing vesicles. These results indicate that vincristine and vinblastine alter plasma cholesterol and triacylglycerol concentrations in part by interfering with hepatic lipid and lipoprotein metabolism. These studies further suggest the possibility that other less cytotoxic alkaloids from Catharanthus species with clinically useful hypocholesterolemic activity may be discovered.     

Temporal Patterns in Seawater Quality from Dredging in Tropical Environments

Maintenance and capital dredging represents a potential risk to tropical environments, especially in turbidity-sensitive environments such as coral reefs. There is little detailed, published observational time-series data that quantifies how dredging affects seawater quality conditions temporally and spatially. This information is needed to test realistic exposure scenarios to better understand the seawater-quality implications of dredging and ultimately to better predict and manage impacts of future projects. Using data from three recent major capital dredging programs in North Western Australia, the extent and duration of natural (baseline) and dredging-related turbidity events are described over periods ranging from hours to weeks. Very close to dredging i.e. <500 m distance, a characteristic features of these particular case studies was high temporal variability. Over several hours suspended sediment concentrations (SSCs) can range from 100–500 mg L-1. Less turbid conditions (10–80 mg L-1) can persist over several days but over longer periods (weeks to months) averages were <10 mg L-1. During turbidity events all benthic light was sometimes extinguished, even in the shallow reefal environment, however a much more common feature was very low light ‘caliginous’ or daytime twilight periods. Compared to pre-dredging conditions, dredging increased the intensity, duration and frequency of the turbidity events by 10-, 5- and 3-fold respectively (at sites <500 m from dredging). However, when averaged across the entire dredging period of 80–180 weeks, turbidity values only increased by 2–3 fold above pre-dredging levels. Similarly, the upper percentile values (e.g., P99, P95) of seawater quality parameters can be highly elevated over short periods, but converge to values only marginally above baseline states over longer periods. Dredging in these studies altered the overall probability density distribution, increasing the frequency of extreme values. As such, attempts to understand the potential biological impacts must consider impacts across telescoping-time frames and changes to extreme conditions in addition to comparing central tendency (mean/median). An analysis technique to capture the entire range of likely conditions over time-frames from hours to weeks is described using a running means/percentile approach.