Winter color polymorphisms identify global hot spots for evolutionary rescue from climate change.

Maintenance of biodiversity in a rapidly changing climate will depend on the efficacy of evolutionary rescue, whereby population declines due to abrupt environmental change are reversed by shifts in genetically driven adaptive traits. However, a lack of traits known to be under direct selection by anthropogenic climate change has limited the incorporation of evolutionary processes into global conservation efforts. In 21 vertebrate species, some individuals undergo a seasonal color molt from summer brown to winter white as camouflage against snow, whereas other individuals remain brown.

Evaluating hydrophobic galactonoamidines as transition state analogs for enzymatic β-galactoside hydrolysis.

A spectroscopic examination of six galactonoamidines with inhibition constants and efficacy in the low nanomolar concentration range (K = 6-11 nM, IC = 12-36 nM) suggested only two of them as putative transition state analogs for the hydrolysis of β-galactosides by β-galactosidase (A. oryzae). A rationale for the experimental results was elaborated using docking and molecular dynamics studies.

Comparative assessment of five trials of universal HIV testing and treatment in sub-Saharan Africa.

Design: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa.

Within-sample variation in snowshoe hare faecal glucocorticoid metabolite measurements.

Faecal glucocorticoid metabolite (FGM) concentrations are used increasingly as a non-invasive measure to index physiological stress experienced by diverse taxa. However, FGM may not be evenly distributed throughout a faecal mass or faecal pellet group. Moreover, within-sample variation in FGM measurements associated with different sampling and/or processing techniques is rarely reported despite potentially having important implications for inferring stress levels in free-ranging wildlife.

Tumour diameter is not reliable for management of non-secreting pancreatic neuroendocrine tumours.

Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs.

Ultrasound for the Diagnosis and Management of Suspected Urolithiasis in the Emergency Department.

Background: This review provides practicing emergency physicians updated information regarding point-of-care ultrasound (POCUS) imaging of patients with suspected urolithiasis.

Methods: A PubMed literature search was conducted for articles published between January 1, 1996 and May 31, 2017 and limited to human clinical trials written in English with relevant keywords. High-quality studies identified then underwent a structured review.

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.

Genetic sampling for estimating density of common species.

Understanding population dynamics requires reliable estimates of population density, yet this basic information is often surprisingly difficult to obtain. With rare or difficult-to-capture species, genetic surveys from noninvasive collection of hair or scat has proved cost-efficient for estimating densities. Here, we explored whether noninvasive genetic sampling (NGS) also offers promise for sampling a relatively common species, the snowshoe hare ( Erxleben, 1777), in comparison with traditional live trapping.

Effect of Genetic Information and Information About Caffeine Content on Caffeine Withdrawal Symptoms.

This study sought to test the effect of genetic information and information about the caffeine content of a beverage on caffeine withdrawal, specifically if: (1) being informed that one has tested positive for a gene related to caffeine withdrawal can produce an exaggerated caffeine withdrawal response during abstinence; (2) belief that one has consumed caffeine leads to a reduction in withdrawal symptoms when no caffeine is consumed. Regular coffee drinkers were given a bogus genetic test and were told either that they had tested positive or negative for a gene related to withdrawal. After 24-hour caffeine abstinence withdrawal symptoms were measured using a self-report caffeine withdrawal scale, and then again after a cup of decaffeinated coffee.

Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines.

Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.

Lack of Cell Proliferative and Tumorigenic Effects of 4-Hydroxyestradiol in the Anterior Pituitary of Rats: Role of Ultrarapid O-Methylation Catalyzed by Pituitary Membrane-Bound Catechol-O-Methyltransferase.

In animal models, estrogens are complete carcinogens in certain target sites. 4-Hydroxyestradiol (4-OH-E), an endogenous metabolite of 17β-estradiol (E), is known to have prominent estrogenic activity plus potential genotoxicity and mutagenicity. We report here our finding that 4-OH-E does not induce pituitary tumors in ACI female rats, whereas E produces 100% pituitary tumor incidence.

Strain Rate in Children and Young Piglets Mirrors Changes in Contractility and Demonstrates a Force-Frequency Relationship.

Background: In adult humans and pig models, strain rate (SR) correlates strongly with invasive measures of contractility but does not demonstrate a force-frequency relationship, which is a fundamental behavior of myocardial contraction. Given the considerable maturational changes of the myocardium from fetal stages to adulthood, extrapolation of adult findings to the young heart may not be appropriate. We sought to evaluate the SR response of the immature heart to increased heart rate (HR) and inotropic stimulation.

The risk of non-union per fracture: current myths and revised figures from a population of over 4 million adults.

Background and purpose - Fracture non-union remains a major clinical problem, yet there are no data available regarding the overall risk of fractures progressing to non-union in a large population. We investigated the rate of non-union per fracture in a large adult population. Methods - National data collected prospectively over a 5-year period and involving just under 5,000 non-unions were analyzed and compared to the incidence of fracture in the same period.

The transcriptional landscape of seasonal coat colour moult in the snowshoe hare.

Seasonal coat colour change is an important adaptation to seasonally changing environments but the evolution of this and other circannual traits remains poorly understood. In this study, we use gene expression to understand seasonal coat colour moulting in wild snowshoe hares (Lepus americanus). We used hair colour to follow the progression of the moult, simultaneously sampling skin from three moulting stages in hares collected during the peak of the spring moult from white winter to brown summer pelage.

Population trends in prenatal detection of transposition of great arteries: impact of obstetric screening ultrasound guidelines.

Objectives: Dextro-transposition of the great arteries (d-TGA) is one of the most common critical neonatal heart defects, with a low detection rate antenatally. We sought to evaluate trends in the prenatal detection of d-TGA with or without ventricular septal defect (VSD) in Alberta over the past 13 years, examining the potential impact of ultrasound guidelines incorporating screening of cardiac outflow tracts, updated in 2009-2010 and in 2013, and factors affecting detection of the condition.

Methods: All fetuses and neonates with d-TGA, with or without VSD, encountered between 2003 and 2015 in the province of Alberta, were identified retrospectively.

Virologic outcomes in early antiretroviral treatment: HPTN 052.

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure.

Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052.

Confidence with and Barriers to Serious Illness Communication: A National Survey of Hospitalists.

Objective: To describe the concerns, confidence, and barriers of practicing hospitalists around serious illness communication.

Background: Hospitalist physicians are optimally positioned to provide primary palliative care, yet their experiences in serious illness communication are not well described.

Methods: Web-based survey, conducted in May 2016.

Mitochondrial Dysfunction in the Pathogenesis of Rett Syndrome: Implications for Mitochondria-Targeted Therapies.

First described over 50 years ago, Rett syndrome (RTT) is a neurodevelopmental disorder caused primarily by mutations of the X-linked gene. RTT affects predominantly females, and has a prevalence of roughly 1 in every 10,000 female births. Prior to the discovery that mutations of are the leading cause of RTT, there were suggestions that RTT could be a mitochondrial disease.

Geographic distribution of California mental health professionals in relation to sociodemographic characteristics.

Objective: To determine whether geographic access to licensed mental health providers in California is a barrier for underserved populations.

Method: Data from the master file of the California Board of Psychology and Board of Behavioral Sciences were merged with U.S.

Psychometric validation of the Anticipated Effects of Alcohol Mixed with Energy Drinks Scale.

Young people are increasingly consuming alcohol mixed with energy drinks (AmEDs). As coingestion of these beverages results in greater adverse consequences than from drinking alcohol alone, we need to understand what factors contribute to and deter coingestion. Existing studies in this area have not utilized a theoretically based or empirically validated measure of outcome expectancies for drinking AmEDs.

Prenatal Diagnosis of the Criss-Cross Heart.

We sought to describe the prenatal features and postnatal outcomes of the "criss-cross heart" (CCH) with crossing atrioventricular connections as encountered in 5 cases and to review the literature regarding fetal diagnoses of this lesion. We reviewed the clinical history and fetal echocardiograms of 5 patients with a diagnosis of CCH encountered in our institution from 2010 to 2015. Affected pregnancies were identified through the University of Alberta fetal cardiology database.

Extensive libraries of gene truncation variants generated by in vitro transposition.

The detailed analysis of the impact of deletions on proteins or nucleic acids can reveal important functional regions and lead to variants with improved macromolecular properties. We present a method to generate large libraries of mutants with deletions of varying length that are randomly distributed throughout a given gene. This technique facilitates the identification of crucial sequence regions in nucleic acids or proteins.

CHARMM force field parameters for 2'-hydroxybiphenyl-2-sulfinate, 2-hydroxybiphenyl, and related analogs.

2'-Hydroxybiphenyl-2-sulfinate (HBPS) desulfinase (DszB) catalyzes the cleavage of the carbon-sulfur bond from HBPS in the final step of microbial 4S pathway desulfurization reactions. DszB is notable for its substrate specificity and exhibits product inhibition, both of which hinder the overall 4S pathway turnover rate. To understand the molecular-level contributions to substrate and inhibitor binding to DszB, we plan to perform molecular dynamic simulations bound to an array of naphthenic molecules and biphenyl analogues of HBPS.

Disease-mediated bottom-up regulation: An emergent virus affects a keystone prey, and alters the dynamics of trophic webs.

Emergent diseases may alter the structure and functioning of ecosystems by creating new biotic interactions and modifying existing ones, producing cascading processes along trophic webs. Recently, a new variant of the rabbit haemorrhagic disease virus (RHDV2 or RHDVb) arguably caused widespread declines in a keystone prey in Mediterranean ecosystems - the European rabbit (Oryctolagus cuniculus). We quantitatively assess the impact of RHDV2 on natural rabbit populations and in two endangered apex predator populations: the Iberian lynx (Lynx pardinus) and the Spanish Imperial eagle (Aquila adalberti).

The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection.

Objectives: A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion.

Methods: Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host.