Molecular and Electrophysiological Characterization of a Novel Cation Channel of Trypanosoma cruzi

We report the identification, functional expression, purification, reconstitution and electrophysiological characterization of a novel cation channel (TcCat) from Trypanosoma cruzi, the etiologic agent of Chagas disease. This channel is potassium permeable and shows inward rectification in the presence of magnesium. Western blot analyses with specific antibodies indicated that the protein is expressed in the three main life cycle stages of the parasite. Surprisingly, the parasites have the unprecedented ability to rapidly change the localization of the channel when they are exposed to different environmental stresses. TcCat rapidly translocates to the tip of the flagellum when trypomastigotes are submitted to acidic pH, to the plasma membrane when epimastigotes are submitted to hyperosmotic stress, and to the cell surface when amastigotes are released to the extracellular medium. Pharmacological block of TcCat activity also resulted in alterations in the trypomastigotes ability to respond to hyperosmotic stress. We also demonstrate the feasibility of purifying and reconstituting a functional ion channel from T. cruzi after recombinant expression in bacteria. The peculiar characteristics of TcCat could be important for the development of specific inhibitors with therapeutic potential against trypanosomes

Additional psychometric data for the Spanish Modified Dental Anxiety Scale, and psychometric data for a Spanish version of the Revised Dental Beliefs Survey

<p>Abstract</p> <p>Background</p> <p>Hispanics comprise the largest ethnic minority group in the United States. Previous work with the Spanish Modified Dental Anxiety Scale (MDAS) yielded good validity, but lower test-retest reliability. We report the performance of the Spanish MDAS in a new sample, as well as the performance of the Spanish Revised Dental Beliefs Survey (R-DBS).</p> <p>Methods</p> <p>One hundred sixty two Spanish-speaking adults attending Spanish-language church services or an Hispanic cultural festival completed questionnaires containing the Spanish MDAS, Spanish R-DBS, and dental attendance questions, and underwent a brief oral examination. Church attendees completed the questionnaire a second time, for test-retest purposes.</p> <p>Results</p> <p>The Spanish MDAS and R-DBS were completed by 156 and 136 adults, respectively. The test-retest reliability of the Spanish MDAS was 0.83 (95% CI = 0.60-0.92). The internal reliability of the Spanish R-DBS was 0.96 (95% CI = 0.94-0.97), and the test-retest reliability was 0.86 (95% CI = 0.64-0.94). The two measures were significantly correlated (Spearman's rho = 0.38, p < 0.001). Participants who do not currently go to a dentist had significantly higher MDAS scores (t = 3.40, df = 106, p = 0.003) as well as significantly higher R-DBS scores (t = 2.21, df = 131, p = 0.029). Participants whose most recent dental visit was for pain or a problem, rather than for a check-up, scored significantly higher on both the MDAS (t = 3.00, df = 106, p = 0.003) and the R-DBS (t = 2.85, df = 92, p = 0.005). Those with high dental fear (MDAS score 19 or greater) were significantly more likely to have severe caries (Chi square = 6.644, df = 2, p = 0.036). Higher scores on the R-DBS were significantly related to having more missing teeth (Spearman's rho = 0.23, p = 0.009).</p> <p>Conclusion</p> <p>In this sample, the test-retest reliability of the Spanish MDAS was higher. The significant relationships between dental attendance and questionnaire scores, as well as the difference in caries severity seen in those with high fear, add to the evidence of this scale's construct validity in Hispanic samples. Our results also provide evidence for the internal and test-retest reliabilities, as well as the construct validity, of the Spanish R-DBS.</p

Functional evolution of nuclear structure

The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis

the European trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA trial).

Background Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. Methods We recruited patients from October, 1997, to June, 2000. 13 655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12 218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4·2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. Findings Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9–29, p=0·0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. Interpretation Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease