Phototaxis signaling by the membrane complex of archaeal sensory rhodopsins and their transducers

Sensory rhodopsins I and II (SRI and SRII) are visual pigment-like phototaxis receptors in the archaeon Halobacterium salinarum. The receptor proteins each consist of a single polypeptide that folds into 7 $\alpha$-helical membrane-spanning segments forming an internal pocket where the chromophore retinal is bound. They transmit signals to their tightly bound transducer proteins, HtrI and HtrII, respectively, which in turn control a phosphotransfer pathway modulating the flagellar motors. SRI-HtrI mediates attractant responses to orange-light and repellent responses to UV light, while SRII-HtrII mediates repellent response to blue light. Experiments were designed to analyze the molecular processes in the SR-Htr complexes responsible for receptor activation, which previously had been shown by our laboratory to involve proton transfer reactions of the retinylidene Schiff base in the photoactive site, transfer of signals from receptor to transducer, and signaling specificity by the receptor-transducer complex.^ Site-directed mutagenesis and laser-flash kinetic spectroscopy revealed that His-166 in SRI (i) plays a role in the proton transfers both to and from the Schiffbase, either as a structurally critical residue or possibly as a direct participant, (ii) is involved in the modulation of SIU photoreaction kinetics by HtrI, and (iii) modulates the pKa of Asp-76, an important residue in the photoactive site, through a long-distance electrostatic interaction. Computerized cell tracking and motion analysis demonstrated that (iv) His-166 is crucial in phototaxis signaling: a spectrum of substitutions either eliminate signaling or greatly perturb the activation process that produces attractant and repellent signaling states of the receptor.^ The signaling states of SRI are communicated to HtrI, whose oligomeric structure and conformational changes were investigated by engineered sulfhydryl probes. It was found that signaling by the SRI-HtrI complex involves reversible conformational changes within a preexisting HtrI dimer, which is likely accomplished through a slight winding or unwinding of the two HtrT monomers via their loose coiled coil association. To elucidate which domains of the Htr dimers confer specificity for interaction with SRI or SRII, chimeras of HtrI and HtrII were constructed. The only determinant needed for functional and specific interaction with SRI or SRII was found to be the four transmembrane segments of the HtrI or HtrII dimers, respectively. The entire cytoplasmic parts of HtrI and HtrII, which include the functionally important signaling and adaptation domains, were interchangeable.^ These observations support a model in which SRI and SRII undergo conformational changes coupled to light-induced proton transfers in their photoactive sites, and that lateral helix-helix interactions with their cognate transducers' 4-helix bundle in the membrane relay these conformational changes into different states of the Htr proteins which regulate the down-stream phosphotransfer pathway. ^

Behavioral risk profile of marathon runners

Although long distance running clearly has benefits--as witnessed by its popularity--it also has risks of injury and death. Little is known, however, about the prevalence of potentially dangerous training habits in long distance runners, although anecdotal information suggests that many runners have erroneous beliefs about risks and benefits of marathon running. We conducted a cross-sectional survey to estimate the prevalence of 19 potentially dangerous training habits (risky behaviors) among marathon runners. A 66-item self-administered questionnaire was mailed to a stratified random sample of runners who finished of the 1992 Houston-Tenneco Marathon and were 21-71 years of age. Responses were obtained from 508 runners (83%) with approximately equal representation in four age-gender groups: men $<$40 years, men $\ge$40 years, women $<$40 years, and women $\ge$40 years.^ Prevalences of risky behaviors were high. 50% or more ran in dangerously hot and humid conditions, did not cool down or stretch after running, did not wear proper running gear, or ran when injured or ill; 25-49% did not warm up, ran on dangerous surfaces, did not drink sufficient water during training, increased weekly mileage too quickly, and ran during lightning storms; 10-24% ran daily, ran in areas with high pollution, ran in the same direction as traffic, did hard runs frequently, ran more than 60 miles per week, or ran against the advice of a physician.^ Positive associations were found between the practice of risky behaviors and self-reported prevalence of musculoskeletal injuries, heat-related injuries, noncompliance with recommendations for preventive health examinations, and noncompliance with positive health habits.^ These results indicate that many marathon runners engage in training habits that may increase risk of substantial injury or illness. Further studies are needed to explore the association of risky training behaviors on the incidence of injuries, and to determine reasons for noncompliance with recommendations from sports medicine specialists. ^

Spatial analysis of water body distance and West Nile Virus human cases in Houston, TX

West Nile Virus (WNV) is an arboviral disease that has affected hundreds of residents in Harris County, Texas since its introduction in 2002. Persistent infection, lingering sequelae and other long-term symptoms of patients reaffirm the need for prevention of this important vector-borne disease. This study aimed to determine if living within 400m of a water body increases one’s odds of infection with WNV. Additionally, we wanted to determine if one’s proximity to a particular water type or water body source increased one’s odds of infection with WNV.^ 145 cases’ addresses were abstracted from the initial interview and consent records from a cohort of patients (Epidemiology of Arboviral Encephalitis in Houston study, HSC-SPH-03-039). After applying inclusion criteria, 140 cases were identified for analysis. 140 controls were selected for analysis using a population proportionate to size model and US Census Bureau data. MapMarker USA v14 was used to geocode the cases’ addresses. Both cases’ and controls’ coordinates were uploaded onto a Harris County water shapefile in MapInfo Professional v9.5.1. Distance in meters to the closest water source, closest water source type, and closest water source name were recorded.^ Analysis of Variance (p=0.329, R2 = 0.0034) indicated no association between water body distance and risk of WNV disease. Living near a creek (x2 = 11.79, p < 0.001), or the combined group of creek and gully (x 2 = 14.02, p < 0.001) were found to be strongly associated with infection of WNV. Living near Cypress Creek and its feeders (x2 = 15.2, p < 0.001) was found to be strongly associated with WNV infection. We found that creek and gully habitats, particularly Cypress Creek, were preferential for the local disease transmitting Culex quinquefasciatus and reservoir avian population.^