Skin Pigmentation and Corneal and Lens Opacities with Prolonged Chlorpromazine Therapy

Previously undescribed ocular and dermatologic complications of prolonged chlorpromazine therapy have been noted in 70 patients of a series of many thousands receiving similar therapy. All affected patients were women who had been receiving high doses of chlorpromazine, averaging 500 to 1500 mg. daily, for at least three to five years before the complications became apparent. Skin manifestations consisted of a peculiar purplish pigmentation of the skin of exposed areas of the face, neck and hands, characterized histologically by deposition of material with the staining properties of melanin in the superficial layers of the dermis, particularly in a perivascular distribution. Ocular complications consisted of granular opacity of the cornea and often of the lens as well, the latter producing a central stellate type of cataract.     

Applying the social–ecological systems framework to the evaluation and design of payment for ecosystem service schemes in the Eurasian steppe

The application of payment for ecosystem services schemes to dryland areas has been limited, particularly for schemes that seek to improve the grassland upon which resource users in these landscapes depend. The high levels of climatic and resource variability, strength of informal institutions governing resource use and contested nature of resource decline are examples of defining characteristics that may challenge the application of more conventional payment for ecosystem services schemes in dryland contexts. We used a social–ecological systems framework to (i) help identify design criteria for effective and efficient payment for ecosystem services schemes in drylands under a pastoral land-use, and (ii) explore the applicability of the framework to dryland areas. Using eco-compensation schemes in the Chinese governed areas of the Eurasian steppe as a case study, we found that the framework adequately identified the need for non-equilibrium dynamics to be incorporated into scheme design. However, the framework was less able to explicitly enunciate the importance of micro-economics and cultural values for scheme viability. In contexts like the Eurasian steppe where some level of grazing may maximise the species richness of grasslands, acknowledging history of use in the resource unit subsystem component of the framework, not just the user subsystem component, would improve the framework. The explicit incorporation of contested issues into the framework is also needed, as dryland areas have a history of being misunderstood by non-dryland cultures, researchers and policymakers. We conclude that tailoring a general diagnostic tool towards the specific social–ecological attributes of the drylands under a pastoral land-use will improve the ability of payment for ecosystem services schemes to reach their conservation aims.     

An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice

We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse Pax8 promoter, directs high levels of expression of the reverse tetracycline-dependent transactivator (rtTA) to all proximal and distal tubules and the entire collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8-rtTA mice with tetracycline-responsive c-MYC mice, we established a new, inducible model of polycystic kidney disease that can mimic adult onset and that shows progression to renal malignant disease. When targeting the expression of transforming growth factor beta-1 to the kidney, we avoided early lethality by discontinuous treatment and successfully established an inducible model of renal fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis complex-1 was achieved, which resulted in the early outgrowth of giant polycystic kidneys reminiscent of autosomal recessive polycystic kidney disease. These experiments establish Pax8-rtTA mice as a powerful tool for modeling renal diseases in transgenic mice.     

Improving subcellular localization prediction using text classification and the gene ontology

MOTIVATION: Each protein performs its functions within some specific locations in a cell. This subcellular location is important for understanding protein function and for facilitating its purification. There are now many computational techniques for predicting location based on sequence analysis and database information from homologs. A few recent techniques use text from biological abstracts: our goal is to improve the prediction accuracy of such text-based techniques. We identify three techniques for improving text-based prediction: a rule for ambiguous abstract removal, a mechanism for using synonyms from the Gene Ontology (GO) and a mechanism for using the GO hierarchy to generalize terms. We show that these three techniques can significantly improve the accuracy of protein subcellular location predictors that use text extracted from PubMed abstracts whose references are recorded in Swiss-Prot.     

Age-dependent plasticity of sex pheromone response in the moth, Agrotis ipsilon: Combined effects of octopamine and juvenile hormone

Male moths use sex pheromones to find their mating partners. In the moth, Agrotis ipsilon, the behavioral response and the neuron sensitivity within the primary olfactory centre, the antennal lobe (AL), to sex pheromone increase with age and juvenile hormone (JH) biosynthesis. By manipulating the JH level, we previously showed that JH controls this age-dependent neuronal plasticity, and that its effects are slow (within 2 days). We hypothesized that the hormonal effect might be indirect, and one neuromodulator candidate, which might serve as a mediator, is octopamine (OA). Here, we studied the effects of OA and an OA receptor antagonist, mianserin, on behavioral and AL neuron responses of mature and immature males during stimulation with sex pheromone. Our results indicate that, although OA injections enhanced the behavioral pheromone response in mature males, OA had no significant effect on behavior in immature males. However, mianserin injections decreased the behavioral response in mature males. AL neuron sensitivity increased after OA treatment in immature males, and decreased after mianserin treatment in mature males. Determination of OA levels in ALs of immature and mature males did not reveal any difference. To study the possible interactive effects of JH and OA, the behavioral pheromone response was analyzed in JH-deprived mature males injected with OA, and in immature males injected with fenoxycarb, a JH agonist, and mianserin. Results show that both JH and OA are necessary to elicit a behavioral response of A. ipsilon males to sex pheromone.     

Endothelial Progenitor Cell Function,Apoptosis, and Telomere Length in Overweight/Obese Humans

Excess adiposity is associated with increased cardiovascular morbidity and mortality. Endothelial progenitor cells (EPCs) play an important role in vascular repair. We tested the hypothesis that increased adiposity is associated with EPC dysfunction, characterized by diminished capacity to release angiogenic cytokines, increased apoptotic susceptibility, reduced cell migration, and shorter telomere length. A total of 67 middle‐aged and older adults (42–67 years) were studied: 25 normal weight (normal weight; BMI: 18.5–24.9 kg/m²) and 42 overweight/obese (overweight/obese; BMI: 25.0–34.9 kg/m²). Cells with phenotypic EPC characteristics were isolated from peripheral blood. EPC release of vascular endothelial growth factor (VEGF) and granulocyte colony–stimulating factor (G‐CSF) was determined in the absence and presence of phytohemagglutinin (10 µg/ml). Intracellular active caspase‐3 and cytochrome c concentrations were determined by immunoassay. Migratory activity of EPCs in response to VEGF (2 ng/ml) and stromal cell–derived factor‐1α (SDF‐1α; 10 ng/ml) was determined by Boyden chamber. Telomere length was assessed by Southern hybridization. Phytohemagglutinin‐stimulated release of VEGF (90.6 ± 7.6 vs. 127.2 ± 11.6 pg/ml) and G‐CSF (896.1 ± 77.4 vs. 1,176.3 ± 126.3 pg/ml) was ～25% lower (P < 0.05) in EPCs from overweight/obese vs. normal weight subjects. Staurosporine induced a ～30% greater (P < 0.05) increase in active caspase‐3 in EPCs from overweight/obese (2.8 ± 0.2 ng/ml) compared with normal weight (2.2 ± 0.2) subjects. There were no significant differences in EPC migration to either VEGF or SDF‐1α. Telomere length did not differ between groups. These results indicate that increased adiposity adversely affects the ability of EPCs to release proangiogenic cytokines and resist apoptosis, potentially compromising their reparative potential.     

Regular Aerobic Exercise,Without Weight Loss,Improves Endothelium‐dependent Vasodilation in Overweight and Obese Adults

Lifestyle modification in the form of weight reduction by caloric restriction alone or in combination with regular aerobic exercise significantly improves endothelium‐dependent vasodilation in overweight and obese adults. We determined whether regular aerobic exercise, independent of weight loss, improves endothelium‐dependent vasodilation in overweight and obese adults. Twenty overweight and obese adults (age 53 ± 1 years; BMI: 30.2 ± 0.8 kg/m²) were studied before and after a 3‐month aerobic exercise training intervention. Forearm blood flow (FBF) responses were determined (via plethysmography) in response to intra‐arterial infusion of acetylcholine and sodium nitroprusside. There were no changes in body mass or composition with the intervention. FBF responses to acetylcholine were ～35% higher (P < 0.01) after (4.1 ± 0.9 to 14.7 ± 4.3 ml/100 ml tissue/min) compared with before (4.2 ± 0.8 to 11.0 ± 3 ml/100 ml tissue/min) exercise training. FBF responses to sodium nitroprusside were unchanged. These results indicate that regular aerobic exercise improves endothelium‐dependent vasodilation in overweight and obese adults, independent of changes in body mass or composition.