Mapping evaporative water loss in desert passerines reveals an expanding threat of lethal dehydration

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources

A national registry study of patient and renal survival in adult nephrotic syndrome

Introduction: We aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS). Methods: We conducted a national registry–based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014–2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population. Results: A total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%–4.6%) versus 0.9% (0.8%–1.0%) in patients aged <60 years and 24.9% (18.4%–30.8%) versus 9.4% (8.3%–10.5%) in those aged ≥60 years. In secondary NS, this discrepancy was 17.1% (5.6%–27.2%) versus 1.1% (0.9%–1.2%) in <60-year-olds and 49.4% (36.6%–59.7%) versus 8.1% (6.6%–9.6%) in ≥60-year-olds. In primary NS, cardiovascular causes accounted for 28% of deaths, compared with 18% in the general population. Eighty patients (15%) progressed to ESKD. Incidence of ESKD by 3 years was 8.4% (95% CI 4.9%–11.7%) in primary and 35.1% (24.3%–44.5%) in secondary NS. Early remission of proteinuria and the absence of early acute kidney injury (AKI) were associated with lower rates of death and ESKD. Conclusions: Adults with NS have high rates of death and ESKD. Cardiovascular causes account for excess mortality in primary NS

Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway

Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway. As with other DNA glycosylases, the abasic product is potentially more harmful than the initial lesion. Since Mug is known to bind its product tightly, inhibiting enzyme turnover, understanding how Mug binds DNA is of significance when considering how Mug interacts with downstream enzymes in the base-excision repair pathway. We have demonstrated differential binding modes of Mug between its substrate and abasic DNA product using both band shift and fluorescence anisotropy assays. Mug binds its product cooperatively, and a stoichiometric analysis of DNA binding, catalytic activity and salt-dependence indicates that dimer formation is of functional significance in both catalytic activity and product binding. This is the first report of cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms the basis of product inhibition in Mug. It therefore provides a new perspective on abasic site protection and the findings are discussed in the context of downstream lesion processing and enzyme communication in the base excision repair pathway

Mutation increasing β-carotene concentrations does not adversely affect concentrations of essential mineral elements in pepper fruit

<div><p>Vitamin and mineral deficiencies are prevalent in human populations throughout the world. Vitamin A deficiency affects hundreds of millions of pre-school age children in low income countries. Fruits of pepper (<i>Capsicum annuum</i> L.) can be a major dietary source of precursors to Vitamin A biosynthesis, such as β-carotene. Recently, pepper breeding programs have introduced the orange-fruited (<i>of</i>) trait of the mutant variety Oranzheva kapiya, which is associated with high fruit β-carotene concentrations, to the mutant variety Albena. In this manuscript, concentrations of β-carotene and mineral elements (magnesium, phosphorus, sulphur, potassium, zinc, calcium, manganese, iron and copper) were compared in fruit from P31, a red-fruited genotype derived from the variety Albena, and M38, a genotype developed by transferring the orange-fruited mutation (<i>of</i>) into Albena. It was observed that fruit from M38 plants had greater β-carotene concentration at both commercial and botanical maturity (4.9 and 52.7 mg / kg fresh weight, respectively) than fruit from P31 plants (2.3 and 30.1 mg / kg fresh weight, respectively). The mutation producing high β-carotene concentrations in pepper fruits had no detrimental effect on the concentrations of mineral elements required for human nutrition.</p></div

Eyes wide open: perceived exploitation and its consequences

Drawing on the array of literature on exploitation from several social science disciplines, we propose a new way of seeing employer-employee relationships by introducing the concept of perceived exploitative employee-organization relationships, distinguish it from related concepts, and conduct five studies to develop a scale and test our theoretical model of the effects of such employee perceptions. Contributing to the Employee-Organization Relationships and workplace emotions literatures, perceived exploitation is defined as employees’ perceptions that they have been purposefully taken advantage of in their relationship with the organization, to the benefit of the organization itself. We propose and find that such perceptions are associated with both outward-focused emotions of anger and hostility toward the organization and inward-focused ones of shame and guilt at remaining in an exploitative job. In two studies including construction workers and a time-lagged study of medical residents, we find that the emotions of anger and hostility partially mediate the effects of perceived exploitation on employee engagement, revenge against the organization, organizational commitment, and turnover intentions, whereas the emotions of shame and guilt partially mediate the effects of perceived exploitation on employee burnout, silence, and psychological withdrawal

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants with Treatment Resistance in Schizophrenia

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P =.001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P =.04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance