Take one

This item contains two issues of the Take One newsletter: January 12, and 26, 1978.Take One was published every two weeks and focused on short news items and announcements "for the people of University Hospital.

Turning Cones Off: the Role of the 9-Methyl Group of Retinal in Red Cones

Our ability to see in bright light depends critically on the rapid rate at which cone photoreceptors detect and adapt to changes in illumination. This is achieved, in part, by their rapid response termination. In this study, we investigate the hypothesis that this rapid termination of the response in red cones is dependent on interactions between the 9-methyl group of retinal and red cone opsin, which are required for timely metarhodopsin (Meta) II decay. We used single-cell electrical recordings of flash responses to assess the kinetics of response termination and to calculate guanylyl cyclase (GC) rates in salamander red cones containing native visual pigment as well as visual pigment regenerated with 11-cis 9-demethyl retinal, an analogue of retinal in which the 9-methyl group is missing. After exposure to bright light that photoactivated more than ∼0.2% of the pigment, red cones containing the analogue pigment had a slower recovery of both flash response amplitudes and GC rates (up to 10 times slower at high bleaches) than red cones containing 11-cis retinal. This finding is consistent with previously published biochemical data demonstrating that red cone opsin regenerated in vitro with 11-cis 9-demethyl retinal exhibited prolonged activation as a result of slowed Meta II decay. Our results suggest that two different mechanisms regulate the recovery of responsiveness in red cones after exposure to light. We propose a model in which the response recovery in red cones can be regulated (particularly at high light intensities) by the Meta II decay rate if that rate has been inhibited. In red cones, the interaction of the 9-methyl group of retinal with opsin promotes efficient Meta II decay and, thus, the rapid rate of recovery

The Development and Implementation of a Culturally Safe Survey for Measuring Knowledge, Attitudes and Values around FASD and Alcohol Use During Pregnancy in a Remote Australian Aboriginal Community Setting

Fetal Alcohol Spectrum Disorder (FASD) describes a lifelong neurodevelopmental disability caused by prenatal alcohol exposure that has a devastating impact on individuals, families and communities. The prevalence of FASD is high in some Indigenous communities around the World and the only active case ascertainment prevalence study conducted in Australia found a rate of 19.44 per 100 children in the remote Fitzroy Valley region of Western Australia. Following this study community led FASD prevention activities were implemented under the Marulu (“Worth Nurturing”) Strategy in the Fitzroy Valley. A Knowledge, Attitudes and Practices survey was designed to assess the impact of the prevention campaign and gather more information about knowledge of the dangers of alcohol use in pregnancy and FASD, local attitudes, and health behaviours both around alcohol and more generally including where residents received their health information. Best practices recommend including local Aboriginal people in the development of surveys and aiming to achieve cultural security. Actions taken included consulting with local health workers during survey development, translation of key sections of the survey into the local Kimberley Kriol, and performing the surveys with the assistance of Aboriginal Community Researchers. The full survey is made available in this paper. The surveys were conducted with 200 community members during August 2015 and 203 in October 2015. Surveys were updated between the first and second waves based on learnings during implementation. Key implementation details around weather and timing, gender/kinship issues, group participation, declining participation, problematic questions and responses to the survey are described. Cultural safety was achieved but further steps could be taken to ensure future cultural security by embedding cultural safety protocols in the survey and further community consultation

Tracking Assaultâ injured, Drugâ using Youth in Longitudinal Research: Followâ up Methods

ObjectivesViolence is one of the leading causes of death among youth ages 14 to 24. Hospitalâ and emergency department (ED)â based violence prevention programs are increasingly becoming a critical part of public health efforts; however, evaluation of prevention efforts is needed to create evidenceâ based best practices. Retention of study participants is key to evaluations, although little literature exists regarding optimizing followâ up methods for violently injured youth. This study aims to describe the methods for retention in youth violence studies and the characteristics of hardâ toâ reach participants.MethodsThe Flint Youth Injury (FYI) Study is a prospective study following a cohort of assaultâ injured, drugâ using youth recruited in an urban ED, and a comparison population of drugâ using youth seeking medical or nonâ violenceâ related injury care. Validated survey instruments were administered at baseline and four followâ up time points (6, 12, 18, and 24 months). Followâ up contacts used a variety of strategies and all attempts were coded by type and level of success. Regression analysis was used to predict contact difficulty and followâ up interview completion at 24 months.ResultsA total of 599 patients (ages 14â 24) were recruited from the ED (mean ± SD age = 20.1 ± 2.4 years, 41.2% female, 58.2% African American), with followâ up rates at 6, 12, 18, and 24 months of 85.3%, 83.7% 84.2%, and 85.3%, respectively. Participant contact efforts ranged from two to 53 times per followâ up time frame to complete a followâ up appointment, and more than 20% of appointments were completed off site at community locations (e.g., participantsâ homes, jail/prison). Participants who were younger (p < 0.05) and female (p < 0.01) were more likely to complete their 24â month followâ up interview. Participants who sought care in the ED for assault injury (p < 0.05) and had a substance use disorder (p < 0.01) at baseline required fewer contact attempts to complete their 24â month followâ up, while participants reporting a fight within the immediate 3 months before their 24â month followâ up (p < 0.01) required more intensive contact efforts.ConclusionsThe FYI study demonstrated that achieving high followâ up rates for a difficultâ toâ track, violentlyâ injured ED population is feasible through the use of established contact strategies and a variety of interview locations. Results have implications for followâ up strategies planned as part of other violence prevention studies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/1/acem13495_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/2/acem13495.pd

Chromophore supply rate-limits mammalian photoreceptor dark adaptation

Efficient regeneration of visual pigment following its destruction by light is critical for the function of mammalian photoreceptors. Here, we show that misexpression of a subset of cone genes in the rd7 mouse hybrid rods enables them to access the normally cone-specific retina visual cycle. The rapid supply of chromophore by the retina visual cycle dramatically accelerated the mouse rod dark adaptation. At the same time, the competition between rods and cones for retina-derived chromophore slowed cone dark adaptation, indicating that the cone specificity of the retina visual cycle is key for rapid cone dark adaptation. Our findings demonstrate that mammalian photoreceptor dark adaptation is dominated by the supply of chromophore. Misexpression of cone genes in rods may represent a novel approach to treating visual disorders associated with mutations of visual cycle proteins or with reduced retinal pigment epithelium function due to aging

Interaction of anticancer reduced Schiff base coumarin derivatives with human serum albumin investigated by fluorescence quenching and molecular modeling

The specific binding of five reduced Schiff base derived 7-amino-coumarin compounds with antitumor activity to human serum albumin, the principal binding protein of blood, was studied by fluorescence spectroscopy. Their conditional binding constants were computed and the reversible binding at the Sudlow’s site I was found to be strong (KD ~ 0.03-2.09 M). Based on the data albumin can provide a depot for the compounds and is responsible for their biodistribution and transport processes. The experimental data is complemented by protein– ligand docking calculations for two representatives which support the observations. The proton dissociation constants of the compounds were also determined by UV-Vis spectrophotometric and fluorometric titrations to obtain the actual charges and distribution of the species in the various protonation states at physiological pH

\u3cem\u3eOAS1\u3c/em\u3e Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher\u27s Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host\u27s ability to resist clinical manifestations associated with WNV infection