Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse

Gross chromosomal rearrangements have the potential to be evolutionarily advantageous to an adapting organism. The generation of a hybrid species increases opportunity for recombination by bringing together two homologous genomes. We sought to define the location of genomic rearrangements in three strains of Saccharomyces pastorianus, a natural lager-brewing yeast hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus, using whole genome shotgun sequencing. Each strain of S. pastorianus has lost species-specific portions of its genome and has undergone extensive recombination, producing chimeric chromosomes. We predicted 30 breakpoints that we confirmed at the single nucleotide level by designing species-specific primers that flank each breakpoint, and then sequencing the PCR product. These rearrangements are the result of recombination between areas of homology between the two subgenomes, rather than repetitive elements such as transposons or tRNAs. Interestingly, 28/30 S. cerevisiae- S. eubayanus recombination breakpoints are located within genic regions, generating chimeric genes. Furthermore we show evidence for the reuse of two breakpoints, located in HSP82 and KEM1, in strains of proposed independent origin

Visitation to Cottonseed Storage Sites by Feral Swine and Evidence of Gossypol Exposure

Texas ranks first in U.S. cotton production, and southern Texas is a major region of production within the state. Within Kleberg County, for example, approximately 16,147 ha are planted in cotton annually, yielding approximately 68,200 bales, or 15,467 metric tons, of cotton (U.S. Department of Agriculture [USDA] 2009). Cotton producers have discovered new uses for cotton ginned by-products, such as hydro-mulch (Holt et al. 2005) used as a protein supplement for range livestock (DelCurto et al. 2000) and white-tailed deer (Odocoileus virginianus; Cooper 2006). Because of this, much of the materials are temporarily stored for later use

GPs’ role in caring for children and young people with life-limiting conditions: a retrospective cohort study

Background: GPs are rarely actively involved in healthcare provision for children and young people (CYP) with life-limiting conditions (LLCs). This raises problems when these children develop minor illness or require management of other chronic diseases. Aim: To investigate the association between GP attendance patterns and hospital urgent and emergency care use. Design and setting: Retrospective cohort study using a primary care data source (Clinical Practice Research Datalink) in England. The cohort numbered 19 888. Method: CYP aged 0–25 years with an LLC were identified using Read codes (primary care) or International Classification of Diseases 10 th Revision (ICD-10) codes (secondary care). Emergency inpatient admissions and accident and emergency (A&E) attendances were separately analysed using multivariable, two-level random intercept negative binomial models with key variables of consistency and regularity of GP attendances. Results: Face-to-face GP surgery consultations reduced, from a mean of 7.12 per person year in 2000 to 4.43 in 2015. Those consulting the GP less regularly had 15% (95% confidence interval [CI] = 10% to 20%) more emergency admissions and 5% more A&E visits (95% CI = 1% to 10%) than those with more regular consultations. CYP who had greater consistency of GP seen had 10% (95% CI = 6% to 14%) fewer A&E attendances but no significant difference in emergency inpatient admissions than those with lower consistency. Conclusion: There is an association between GP attendance patterns and use of urgent secondary care for CYP with LLCs, with less regular GP attendance associated with higher urgent secondary healthcare use. This is an important area for further investigation and warrants the attention of policymakers and GPs, as the number of CYP with LLCs living in the community rises

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

Improving the safety and experience of transitions from hospital to home : a cluster randomised controlled feasibility trial of the Your Care Needs You Intervention versus usual care

Background: The ‘Your Care Needs You’ (YCNY) intervention aims to increase the safety and experience of transitions for older people through greater patient involvement during the hospital stay. Methods: A cluster-randomised controlled feasibility trial was conducted on NHS inpatient wards (clusters) where ≥40% were routinely ≥75 years. Wards were randomised to YCNY or usual care using an unequal allocation ratio (3:2). We aimed to recruit up to 20 patients per ward. Follow-up included routine data collection and questionnaires at 5, 30 and 90-days post-discharge. Eligible patients were ≥75, discharged home, stayed overnight on participating wards, and could read and understand English. The trial assessed the feasibility of delivering YCNY and the trial methodology through recruitment rates, outcome completion rates, and a qualitative evaluation. The accuracy of using routinely coded data for the primary outcome in the definitive trial was assessed by extracting discharge information for up to ten non-individual consenting patients per ward. Results: Ten wards were randomised (6 intervention, 4 control). One ward withdrew and two wards were unable to deliver the intervention. 721 patients were successfully screened, and 161 were recruited (95 intervention, 66 control). The patient post-discharge attrition rate was 17.4% (n=28). Primary outcome data were gathered for 91.9% of participants with 75.2% and 59.0% providing secondary outcome data at 5 and 30 days post discharge respectively. Item completion within questionnaires was generally high. Post-discharge follow-up was terminated early due to the COVID-19 pandemic affecting 90 day response rates (16.8%). Data from 88 non-individual consenting patients identified an error rate of 15% when using routinely coded data for the primary outcome. No unexpected serious adverse events were identified. Most patients viewed YCNY favourably. Staff agreed with it in principle, but ward pressures and organisational contexts hampered implementation. There was a need to sustain engagement, provide clarity on roles and responsibilities, and account for fluctuations in patients’ health, capacity, and preferences. Conclusions: If implementation challenges can be overcome, YCNY represents a step towards involving older people as partners in their care to improve the safety and experience of their transitions from hospital to home. Trial registration: ISRCTN: 5115494

Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival

Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.Fil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Singhal, Sandeep K.. Columbia University; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yi, Dae Ik. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Caban, Ambar. Columbia University Medical Center; Estados UnidosFil: Jones, Alana. National Institutes of Health; Estados UnidosFil: Mukhopadhyay, Partha. Columbia University Medical Center; Estados UnidosFil: Gille, Sarah. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. No especifíca;Fil: Newman, Lisa. No especifíca;Fil: Davis, Melissa B.. Henry Ford Health System; Estados UnidosFil: Jenkins, Brittany D.. Henry Ford Health System; Estados UnidosFil: Sepulveda, Jorge L.. Columbia University Medical Center; Estados UnidosFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nápoles, Anna María. National Institute On Minority Health And Health Disparities; Estados UnidosFil: Vohra, Nasreen A.. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University Medical Center; Estados Unido

Navigating to new frontiers in behavioral neuroscience: traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze

We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller's classic description of a processing-inclusive human working memory capacity of 7 ± 2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning

The relationships between perfectionism, pathological worry and generalised anxiety disorder

Background: The relationships between perfectionism, pathological worry and generalised anxiety disorder (GAD) were investigated in a clinical sample presenting for treatment of perfectionism. Method: This study explored the utility of perfectionism in predicting pathological worry in a sample of individuals with elevated perfectionism and GAD (n = 36). Following this, the study examined whether perfectionism could predict a principal GAD diagnosis in the full sample (n = 42).Results: Scores on the perfectionism dimensions Concern over Mistakes, Personal Standards, and Clinical Perfectionism significantly predicted pathological worry among participants with GAD after controlling for gender and depression. The perfectionism dimension Doubts about Actions significantly predicted whether individuals from the full sample received a principal diagnosis of GAD. Conclusions: These findings support certain dimensions of perfectionism having significant associations with pathological worry and GAD

Genome-Wide Association Reveals Pigmentation Genes Play a Role in Skin Aging

Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait (p = 4.1 × 10-9); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (p = 8.8 × 10-13), and rs4268748 near MC1R (p = 1.2 × 10-15). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinate of skin aging

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures