Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma

The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed.     

Ticks (Acari: Ixodidae) of the state of Amazonas,Brazil

The tick fauna of Brazil is currently composed by 72 species. The state of Amazonas is the largest of Brazil, with an area of ≈ 19% of the Brazilian land. Besides its vast geographic area, only 19 tick species have been reported for Amazonas. Herein, lots containing ticks from the state of Amazonas were examined in three major tick collections from Brazil. A total of 5933 tick specimens were examined and recorded, comprising 2693 males, 1247 females, 1509 nymphs, and 484 larvae. These ticks were identified into the following 22 species: Amblyomma cajennense sensu lato, Amblyomma calcaratum, Amblyomma coelebs, Amblyomma dissimile, Amblyomma dubitatum, Amblyomma geayi, Amblyomma goeldii, Amblyomma humerale, Amblyomma latepunctatun, Amblyomma longirostre, Amblyomma naponense, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma rotundatum, Amblyomma scalpturatum, Amblyomma varium, Dermacentor nitens, Haemaphysalis juxtakochi, Ixodes cf. Ixodes fuscipes, Ixodes luciae, Rhipicephalus microplus, Rhipicephalus sanguineus sensu lato. Ticks were collected from 17 (27.4%) out of the 62 municipalities that currently compose the state of Amazonas. The following four species are reported for the first time in the state of Amazonas: A. coelebs, A. dubitatum, H. juxtakochi, and Ixodes cf. I. fuscipes. The only tick species previously reported for Amazonas and not found in the present study is Amblyomma parvum. This study provides a great expansion of geographical and host records of ticks for the state of Amazonas, which is now considered to have a tick fauna composed by 23 species. It is noteworthy that we report 1391 Amblyomma nymphs that were identified to 13 different species.     

Development of a RIVPACS-type predictive model for bioassessment of wadeable streams in Wyoming

RIVPACS models produce a community-level measure of biological condition known as O/E, which is derived from a comparison of the observed (O) biota with those expected (E) to occur in the absence of anthropogenic stress. We used benthic macroinvertebrate and environmental data collected at 925 stream monitoring stations, from 1993 to 2001, to develop, validate, and apply a RIVPACS model to assess the biological condition of wadeable streams in Wyoming. From this dataset, 296 samples were identified as reference, 157 of which were used to calibrate the model, 46 to validate it, and 93 to examine temporal variability in reference site O/E-values. We used cluster analyses to group the model development reference sites into biologically similar classes of streams and multiple discriminant function analysis to determine which environmental variables best discriminated among reference groups. A suite of 14 categorical and continuous environmental variables best discriminated among 15 reference groups and explained a large proportion of the natural variability in biota within the reference dataset. Eleven of the predictor variables were derived from GIS. As expected, mean O/E-values for reference sites used in model development and validation were near unity and statistically similar. Temporal variability in O/E-values for reference sites was low. Test site values ranged from 0 to 1.45 (mean = 0.73). The model was accurate in both space and time and precise enough (S.D. of O/E-values for calibration data = 0.17) to detect modest alteration in biota associated with anthropogenic stressors. Our model was comparable in performance to other RIVPACS models developed in the United States and can produce effective assessments of biological condition over a broad, ecologically diverse region. We also provide convincing evidence that RIVPACS models can be developed primarily with GIS-based predictor variables. This framework not only simplifies the extraction of predictor variable information while potentially reducing expenditures of time and money in the collection of predictor variable information, but opens the door for development and/or application of RIVPACS models in regions where there is a paucity of local-scale, abiotic information.     

Identifying and prioritizing greater sage-grouse nesting and brood-rearing habitat for conservation in human-modified landscapes

Background

Balancing animal conservation and human use of the landscape is an ongoing scientific and practical challenge throughout the world. We investigated reproductive success in female greater sage-grouse (Centrocercus urophasianus) relative to seasonal patterns of resource selection, with the larger goal of developing a spatially-explicit framework for managing human activity and sage-grouse conservation at the landscape level.

Methodology/Principal Findings

We integrated field-observation, Global Positioning Systems telemetry, and statistical modeling to quantify the spatial pattern of occurrence and risk during nesting and brood-rearing. We linked occurrence and risk models to provide spatially-explicit indices of habitat-performance relationships. As part of the analysis, we offer novel biological information on resource selection during egg-laying, incubation, and night. The spatial pattern of occurrence during all reproductive phases was driven largely by selection or avoidance of terrain features and vegetation, with little variation explained by anthropogenic features. Specifically, sage-grouse consistently avoided rough terrain, selected for moderate shrub cover at the patch level (within 90 m²), and selected for mesic habitat in mid and late brood-rearing phases. In contrast, risk of nest and brood failure was structured by proximity to anthropogenic features including natural gas wells and human-created mesic areas, as well as vegetation features such as shrub cover.

Conclusions/Significance

Risk in this and perhaps other human-modified landscapes is a top-down (i.e., human-mediated) process that would most effectively be minimized by developing a better understanding of specific mechanisms (e.g., predator subsidization) driving observed patterns, and using habitat-performance indices such as those developed herein for spatially-explicit guidance of conservation intervention. Working under the hypothesis that industrial activity structures risk by enhancing predator abundance or effectiveness, we offer specific recommendations for maintaining high-performance habitat and reducing low-performance habitat, particularly relative to the nesting phase, by managing key high-risk anthropogenic features such as industrial infrastructure and water developments.     

The Gap1 general amino acid permease acts as an amino acid sensor for activation of protein kinase A targets in the yeast Saccharomyces cerevisiae

Addition of a nitrogen source to yeast (Saccharomyces cerevisiae) cells starved for nitrogen on a glucose-containing medium triggers activation of protein kinase A (PKA) targets through a pathway that requires for sustained activation both a fermentable carbon source and a complete growth medium (fermentable growth medium induced or FGM pathway). Trehalase is activated, trehalose and glycogen content as well as heat resistance drop rapidly, STRE-controlled genes are repressed, and ribosomal protein genes are induced. We show that the rapid effect of amino acids on these targets specifically requires the general amino acid permease Gap1. In the gap1Delta strain, transport of high concentrations of l-citrulline occurs at a high rate but without activation of trehalase. Metabolism of the amino acids is not required. Point mutants in Gap1 with reduced or deficient transport also showed reduced or deficient signalling. However, two mutations, S391A and S397A, were identified with a differential effect on transport and signalling for l-glutamate and l-citrulline. Specific truncations of the C-terminus of Gap1 (e.g. last 14 or 26 amino acids) did not reduce transport activity but caused the same phenotype as in strains with constitutively high PKA activity also during growth with ammonium as sole nitrogen source. The overactive PKA phenotype was abolished by mutations in the Tpk1 or Tpk2 catalytic subunits. We conclude that Gap1 acts as an amino acid sensor for rapid activation of the FGM signalling pathway which controls the PKA targets, that transport through Gap1 is connected to signalling and that specific truncations of the C-terminus result in permanently activating Gap1 alleles.     

Tome-1, a trigger of mitotic entry,is degraded during G1 via the APC

Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cdk1/cyclin B activity and thus mitotic entry and exit.     

Frequency tuning in the electroreceptive periphery.

Our studies are concerned with the frequency tuning that is provided by the electrical resonance of tuberous electroreceptors. Frequency selectivity had previously been measured in the electroreceptor's afferent fibers, and resonant conductances in the electroreceptor cell membrane had been implicated in producing the selectivity. With transdermal application of sinusoidal current, we measured the frequency dependence of the impedance of small areas of the electroreceptor/skin structure of the weakly electric fish Sternopygus and Eigenmannia, and used our data to make a quantitative linear model of the structure. The qualitative form of the model was proposed by Bennett (1). The quantitative model allows us to estimate the frequency selectivity of the voltage across the innervated membrane of the electroreceptor cells. The frequency selectivity of electroreceptor cell voltage derived from our data are as sharp as the neural selectivity at frequencies close to the most sensitive frequency. Many of our measurements supported the linear system model. However, spontaneous electroreceptor voltage oscillations were detected in some of our specimens, suggesting that the electroreceptors can operate in a regime of active nonlinearity. A simple explanation for the observed oscillations is that they arise when damping in the electroreceptor cell's resonant membrane is negative for a limited span of membrane voltage surrounding the resting voltage. The response of oscillating units to sinusoidal current was compatible with this explanation. We report experimental observations bearing on the consequences of active nonlinearity for the frequency tuning of a resonant system.