Gawky is a component of cytoplasmic mRNA processing bodies required for early Drosophila development

In mammalian cells, the GW182 protein localizes to cytoplasmic bodies implicated in the regulation of messenger RNA (mRNA) stability, translation, and the RNA interference pathway. Many of these functions have also been assigned to analogous yeast cytoplasmic mRNA processing bodies. We have characterized the single Drosophila melanogaster homologue of the human GW182 protein family, which we have named Gawky (GW). Drosophila GW localizes to punctate, cytoplasmic foci in an RNA-dependent manner. Drosophila GW bodies (GWBs) appear to function analogously to human GWBs, as human GW182 colocalizes with GW when expressed in Drosophila cells. The RNA-induced silencing complex component Argonaute2 and orthologues of LSm4 and Xrn1 (Pacman) associated with 5′–3′ mRNA degradation localize to some GWBs. Reducing GW activity by mutation or antibody injection during syncytial embryo development leads to abnormal nuclear divisions, demonstrating an early requirement for GWB-mediated cytoplasmic mRNA regulation. This suggests that gw represents a previously unknown member of a small group of genes that need to be expressed zygotically during early embryo development

Artificial intelligence exceeds humans in epidemiological job coding

BACKGROUND: Work circumstances can substantially negatively impact health. To explore this, large occupational cohorts of free-text job descriptions are manually coded and linked to exposure. Although several automatic coding tools have been developed, accurate exposure assessment is only feasible with human intervention. METHODS: We developed OPERAS, a customizable decision support system for epidemiological job coding. Using 812,522 entries, we developed and tested classification models for the Professions et Catégories Socioprofessionnelles (PCS)2003, Nomenclature d'Activités Française (NAF)2008, International Standard Classifications of Occupation (ISCO)-88, and ISCO-68. Each code comes with an estimated correctness measure to identify instances potentially requiring expert review. Here, OPERAS' decision support enables an increase in efficiency and accuracy of the coding process through code suggestions. Using the Formaldehyde, Silica, ALOHA, and DOM job-exposure matrices, we assessed the classification models' exposure assessment accuracy. RESULTS: We show that, using expert-coded job descriptions as gold standard, OPERAS realized a 0.66-0.84, 0.62-0.81, 0.60-0.79, and 0.57-0.78 inter-coder reliability (in Cohen's Kappa) on the first, second, third, and fourth coding levels, respectively. These exceed the respective inter-coder reliability of expert coders ranging 0.59-0.76, 0.56-0.71, 0.46-0.63, 0.40-0.56 on the same levels, enabling a 75.0-98.4% exposure assessment accuracy and an estimated 19.7-55.7% minimum workload reduction. CONCLUSIONS: OPERAS secures a high degree of accuracy in occupational classification and exposure assessment of free-text job descriptions, substantially reducing workload. As such, OPERAS significantly outperforms both expert coders and other current coding tools. This enables large-scale, efficient, and effective exposure assessment securing healthy work conditions

Implementing Electronic Tablet-Based Education of Acute Care Patients

Poor education-related discharge preparedness for patients with heart failure is believed to be a major cause of avoidable rehospitalizations. Technology-based applications offer innovative educational approaches that may improve educational readiness for patients in both inpatient and outpatient settings; however, a number of challenges exist when implementing electronic devices in the clinical setting. Implementation challenges include processes for "on-boarding" staff, mediating risks of cross-contamination with patients' device use, and selling the value to staff and health system leaders to secure the investment in software, hardware, and system support infrastructure. Strategies to address these challenges are poorly described in the literature. The purpose of this article is to present a staff development program designed to overcome challenges in implementing an electronic, tablet-based education program for patients with heart failure

Ecological homogenization of oil Properties in the American Residential Macrosystem

The conversion of native ecosystems to residential ecosystems dominated by lawns has been a prevailing land-use change in the United States over the past 70 years. Similar development patterns and management of residential ecosystems cause many characteristics of residential ecosystems to be more similar to each other across broad continental gradients than that of former native ecosystems. For instance, similar lawn management by irrigation and fertilizer applications has the potential to influence soil carbon (C) and nitrogen (N) pools and processes. We evaluated the mean and variability of total soil C and N stocks, potential net N mineralization and nitrification, soil nitrite (NO2−)/nitrate (NO3−) and ammonium (NH4+) pools, microbial biomass C and N content, microbial respiration, bulk density, soil pH, and moisture content in residential lawns and native ecosystems in six metropolitan areas across a broad climatic gradient in the United States: Baltimore, MD (BAL); Boston, MA (BOS); Los Angeles, CA (LAX); Miami, FL (MIA); Minneapolis–St. Paul, MN (MSP); and Phoenix, AZ (PHX). We observed evidence of higher N cycling in lawn soils, including significant increases in soil NO2−/NO3−, microbial N pools, and potential net nitrification, and significant decreases in NH4+ pools. Self-reported yard fertilizer application in the previous year was linked with increased NO2−/ NO3− content and decreases in total soil N and C content. Self-reported irrigation in the previous year was associated with decreases in potential net mineralization and potential net nitrification and with increases in bulk density and pH. Residential topsoil had higher total soil C than native topsoil, and microbial biomass C was markedly higher in residential topsoil in the two driest cities (LAX and PHX). Coefficients of variation for most biogeochemical metrics were higher in native soils than in residential soils across all cities, suggesting that residential development homogenizes soil properties and processes at the continental scale

«Ахеменидская Авеста» через призму античных источников

The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects' jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20-50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79-0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in the future epidemiologic analyses

Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria

Agonists targeting the kappa opioid receptor (KOR) have been promising therapeutic candidates because of their efficacy for treating intractable itch and relieving pain. Unlike typical opioid narcotics, KOR agonists do not produce euphoria or lead to respiratory suppression or overdose. However, they do produce dysphoria and sedation, side effects that have precluded their clinical development as therapeutics. KOR signaling can be fine-tuned to preferentially activate certain pathways over others, such that agonists can bias signaling so that the receptor signals through G proteins rather than other effectors such as βarrestin2. We evaluated a newly developed G protein signaling–biased KOR agonist in preclinical models of pain, pruritis, sedation, dopamine regulation, and dysphoria. We found that triazole 1.1 retained the antinociceptive and antipruritic efficacies of a conventional KOR agonist, yet it did not induce sedation or reductions in dopamine release in mice, nor did it produce dysphoria as determined by intracranial self-stimulation in rats. These data demonstrated that biased agonists may be used to segregate physiological responses downstream of the receptor. Moreover, the findings suggest that biased KOR agonists may present a means to treat pain and intractable itch without the side effects of dysphoria and sedation and with reduced abuse potential

Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage

Aims/hypothesis Enteroviral infection has been implicated consistently as a key environmental factor correlating with the appearance of autoimmunity and/or the presence of overt type 1 diabetes, in which pancreatic insulin-producing beta cells are destroyed by an autoimmune response. Genetic predisposition through variation in the type 1 diabetes risk gene IFIH1 (interferon induced with helicase C domain 1), which encodes the viral pattern-recognition receptor melanoma differentiation-associated protein 5 (MDA5), supports a potential link between enterovirus infection and type 1 diabetes. Methods We used molecular techniques to detect enterovirus RNA in peripheral blood samples (in separated cellular compartments or plasma) from two cohorts comprising 79 children or 72 adults that include individuals with and without type 1 diabetes who had multiple autoantibodies. We also used immunohistochemistry to detect the enteroviral protein VP1 in the pancreatic islets of post-mortem donors (n=43) with type 1 diabetes. Results We observed enhanced detection sensitivity when sampling the cellular compartment compared with the non-cellular compartment of peripheral blood (OR 21.69; 95% CI 3.64, 229.20; p Conclusions/interpretation Our data indicate that, in peripheral blood, antigen-presenting cells are the predominant source of enterovirus infection, and that infection is correlated with disease stage and genetic predisposition, thereby supporting a role for enterovirus infection prior to disease onset.Peer reviewe

A Multi-City Comparison of Front and Backyard Differences in Plant Species Diversity and Nitrogen Cycling in Residential landscapes

We hypothesize that lower public visibility of residential backyards reduces households’ desire for social conformity, which alters residential land management and produces differences in ecological composition and function between front and backyards. Using lawn vegetation plots (7 cities) and soil cores (6 cities), we examine plant species richness and evenness and nitrogen cycling of lawns in Boston, Baltimore, Miami, Minneapolis-St. Paul, Phoenix, Los Angeles (LA), and Salt Lake City (SLC). Seven soil nitrogen measures were compared because different irrigation and fertilization practices may vary between front and backyards, which may alter nitrogen cycling in soils. In addition to lawn-only measurements, we collected and analyzed plant species richness for entire yards—cultivated (intentionally planted) and spontaneous (self-regenerating)—for front and backyards in just two cities: LA and SLC. Lawn plant species and soils were not different between front and backyards in our multi-city comparisons. However, entire-yard plant analyses in LA and SLC revealed that frontyards had significantly fewer species than backyards for both cultivated and spontaneous species. These results suggest that there is a need for a more rich and social-ecologically nuanced understanding of potential residential, household behaviors and their ecological consequences

Understanding potential career changers’ experience of career confidence following a positive psychology based coaching programme

Changes in the labour market over the last decades have led to an increase in the number of career and job changes individuals are likely to face in their working lives. Previous research indicates that a high level of confidence can help individuals to make positive career changes, yet an agreed definition of confidence is not widely accepted, and the literature provides a limited evidence base for practice. This research involved five female participants who were contemplating a career change. They took part in a coaching programme which consisted of four positive psychology interventions based on a proposal of core confidence as a higher order construct composed of self-efficacy, hope, optimism and resilience. Data were gathered through semi-structured interviews and written reflections and an interpretative phenomenological analysis showed that participants perceived their career confidence before the programme as low, incorporating negative affect and self-doubt. After the programme, participants demonstrated increased career engagement, self-awareness and a positive and optimistic outlook. The analysis revealed that change was effected through the development of hope, change in cognitive processes and coaching as a catalyst. Implications for the definition of career confidence, and for positive psychology and career coaching practice are considered