Decay of an active GPCR: Conformational dynamics govern agonist rebinding and persistence of an active, yet empty, receptor state

G protein-coupled receptors (GPCRs) represent a major pharmaceutical drug target. However, one exception has been the visual photoreceptor rhodopsin, long considered “different” due to its covalently bound, light-sensitive retinal ligands. Here we demonstrate that, in contrast to prior assumptions, release of the agonist all-trans retinal (ATR) is not an irreversible process. Instead, during decay of the active species, ATR can rebind any rhodopsin remaining in an active-like conformation, and this active-like state can transiently persist even after agonist dissociation. These insights demonstrate rhodopsin behaves like other diffusible ligand-binding GPCRs and raise the possibility of treating rhodopsin by pharmaceutical agents

Correcting for enzyme immunoassay changes in long term monitoring studies

Enzyme immunoassays (EIAs) are a common tool for measuring steroid hormones in wildlife due to their low cost, commercial availability, and rapid results. Testing technologies improve continuously, sometimes requiring changes in protocols or crucial assay components. Antibody replacement between EIA kits can cause differences in EIA sensitivity, which can hinder monitoring hormone concentration over time. The antibody in a common cortisol EIA kit used for long-term monitoring of stress in wildlife was replaced in 2014, causing differences in cross reactivity and standard curve concentrations. Therefore, the objective of this study was to develop a method to standardize results following changes in EIA sensitivity. We validated this method using cortisol concentrations measured in the hair of brown bears (Ursus arctos). • We used a simple linear regression to model the relationship between cortisol concentrations using kit 1 and kit 2. • We found a linear relationship between the two kits (R2 = 0.85) and used the regression equation (kit2 = (0.98 × kit1) + 1.65) to predict cortisol concentrations in re-measured samples. • Mean predicted percent error was 16% and 72% of samples had a predicted percent error <20%, suggesting that this method is well-suited for correcting changes in EIA sensitivity.publishedVersio

Estimating minimally important differences for two visionspecific quality of life measures,”

PURPOSE. To estimate minimally important differences (MIDs) for the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ). METHODS. A total of 607 subjects with newly-diagnosed open-angle glaucoma (OAG) was enrolled in the Collaborative Initial Glaucoma Treatment Study (CIGTS) and randomized to initial treatment with medications or surgery. Subjects underwent an ophthalmic examination and telephone-administered quality of life (QOL) interview before randomization and every six months thereafter. The VAQ and NEI-VFQ were used to assess participants&apos; perceptions of their visual function. Clinical measures included the mean deviation (MD) from Humphrey 24-2 full threshold visual field (VF) testing, and best-corrected visual acuity (VA) measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Anchor-based (using MD and VA) and distribution-based methods were used to estimate MIDs. RESULTS. Anchor-based cross-sectional analyses at 66 months follow-up found a 10-letter increment in better eye VA corresponded to MIDs of 5.2 units for VAQ and 3.8 units for NEI-VFQ total scores. A 3-dB increment in the better eye MD yielded MIDs of 2.6 and 2.3 units for the same two questionnaires. In longitudinal analyses, MIDs for the VAQ were 3.2 units for a 10-letter change of VA and 3.4 units for a 3-dB change in the MD. Distribution-based MIDs were larger. CONCLUSIONS. A range of MIDs for the VAQ (2.6-6.5 units) and NEI-VFQ (2.3-3.8 units) was found. Although similar in magnitude, MIDs were sensitive to the MID estimation method, the anchor chosen, and differences between questionnaires. (ClinicalTrials.gov number, NCT00000149.

Hair cortisol concentration and body mass in moose (Alces alces) infested with deer keds (Lipoptena cervi)

The deer ked (Lipoptena cervi), a hematophagous ectoparasite of cervids, is currently spreading in Scandinavia, and the moose (Alces alces) is its main host. However, little is known about the impact of deer keds on moose. We analyzed the hair cortisol concentration (HCC) from 262 moose harvested in the fall in relation to age class, sex, body mass (BM), and deer ked infestation intensity, and BM in relation to age class, sex, and infestation intensity. We found that HCC decreased with increasing deer ked intensity at low ked intensities, but for the higher levels of ked intensities, there was a positive relationship between HCC and ked intensity. The HCC was higher in males than in females and lower in yearlings than in calves and adults. Our failure to find any association between BM and deer ked intensity suggested a negligible impact of deer ked infestation on moose foraging and metabolism at the level of infestation observed early in the infestation, but did not exclude an effect later in winter. Our findings suggested that moose generally tolerated moderate parasitism by keds. However, the increase in HCC at higher ked intensities suggested that the tolerance strategy could be disrupted with further increases in intensities and consequently may negatively affect animal health and welfare

Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening

Abstract Background The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer. Methods/design The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20–45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors’ high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors’: a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives’ baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention. Discussion The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics. Trial registration NCT01612338http://deepblue.lib.umich.edu/bitstream/2027.42/112835/1/12885_2012_Article_3739.pd

The Ursinus Weekly, March 3, 1978

Ursinus news in brief: Fields gets Ph.D.; Ursinus appoints P.R. director; Dining committee meets; P.E. speakers; Pollick attends pool finals • Energy conservation: The Choice is yours • New gym hours proposed • Sakell replaces Dempsey • Cat placed • Comment: Testimonials • Union answers questions • Letters to the editor • Ruby seeks editor • As you like it: Out of this world • The \u2778 Lantern • Cogger announces placement services • Puppeteer performs • College Bowl held • Crosswinds comes to Ursinus • Grapplers troubled • Four meet streak • Victory for women\u27s b-ballhttps://digitalcommons.ursinus.edu/weekly/1082/thumbnail.jp