Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

Biological and mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here we present the experimental and clinical evidence revealing important role of IDAGL in human diseases. Targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple intergenic disease-associated genomic loci (IDAGL) and identifies 96 small non-coding trans-regulatory RNAs of ~ 100-300 nt in length containing SNPs associated with 21 common human disorders (snpRNAs). Functionality of snpRNAs is supported by multiple independent lines of experimental evidence demonstrating their cell-type-specific expression and evolutionary conservation of sequences, genomic coordinates, and biological effects. Analysis of chromatin state signatures, expression profiling experiments using microarray and Q-PCR technologies, and luciferase reporter assays indicate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically-relevant phenotypic changes: NLRP1-locus snpRNAs exert regulatory effects on monocyte/macrophage trans-differentiation, induce prostate cancer (PC) susceptibility snpRNAs, and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific “decoy” targets of microRNAs which function as SNP-allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating androgen depletion-independent growth (ADIG) in vitro and castration-resistant (CR) phenotype in vivo of PC contain intergenic 8q24-locus SNP variants which were recently linked with increased risk of developing PC. Expression level of 8q24-locus PC susceptibility snpRNAs is regulated by NLRP1-locus snpRNAs, which are transcribed from the intergenic long-range enhancer sequence located in 17p13 region at ~ 30 kb distance from the NLRP1 gene. Q-PCR analysis of clinical PC samples reveals markedly increased snpRNA expression levels in tumor tissues compared to the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001); for NLRP1-locus and 8q24-locus SnpRNAs, respectively]. Highly concordant expression profiles of the NLRP1-locus snpRNAs and 8q24 CR-locus snpRNAs (r = 0.896; p < 0.0001) in clinical PC samples and experimental evidence of trans-regulatory effects of NLRP1-locus snpRNAs on expression of 8q24-locus SnpRNAs indicate that ADIG and CR phenotype of human PC cells can be triggered by RNA molecules transcribed from the NLRP1-locus intergenic enhancer and down-stream activation of the 8q24-locus snpRNAs. Our results define the intergenic NLRP1 and 8q24 regions as regulatory loci of ADIG and CR phenotype of human PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC, and identify novel diagnostic and therapeutic targets exploration of which should be highly beneficial for clinical management of PC

Gambling Treatment Diversion Court: First in Nevada

The first Gambling Treatment Diversion Court was established in Las Vegas, Nevada in fall of 2018 following more than 25 years of effort by passionately concerned non-profit Executives, therapists, lawyers and judges. This panel represents one leader from each of those areas, including Judge Cheryl Moss, the first judge to open the Gambling Treatment Diversion Court (GTDC), Dayvid Figler, the first attorney to successfully represent a gambling client and refer her to the GTDC, Carol O\u27Hare, Executive Director of the non-profit Nevada Council on Problem Gambler with 25+ years leadership and advocacy for problem gamblers, Sydney Smith, M.A., Clinical Director of RISE treatment center in Las Vegas and nationally- and state-certified gambling counselor, and Denise F. Quirk, M.A., Clinical Director of the Reno Problem Gambling Center and nationally- and Nevada-certified problem gambling counselor and instructor at the University of Nevada, Reno. The panel will share the development of gambling diversion treatment, legal challenges and victories, the process of the GTDC, case studies of individuals with Gambling Disorder who have endured and succeeded in the legal process, and discussion relevant to the impact of the gambling diversion process at all levels of evaluation, advocacy, treatment and support for gamblers and communities

Industry Career Guide Ownership Dwellings and Real Estate

This industry career guide on Ownership Dwelling and Real Estate (ODRE) aims to inform readers of the range of career options that are open to those who want to work in the industry. By presenting an array of occupations typically found in this field, the reader is informed of the basic requirements to land a specific job in this industry, the associated job environment and possibilities for job movement either in terms of promotion and/or moving laterally from one type of job to another within the industry. In the context of discussing job prospects, it lays out the issues surrounding employment, particularly gaps in job requirements and job candidates’ skills which typically plague other industries. Lastly, it presents the outlook for the housing industry, underscoring the industry’s likely direction in terms of performance and labor market interface within the next short run cycle, and suggests potential areas of cooperation among the academe, private business sector, and concerned government agencies to ensure a sustainable stream of gainful employment opportunities in the housing industry

Ambulatory Care Skills: Do Residents Feel Prepared?

Abstract: Objective: To determine resident comfort and skill in performing ambulatory care skills. Methods: Descriptive survey of common ambulatory care skills administered to internal medicine faculty and residents at one academic medical center. Respondents were asked to rate their ability to perform 12 physical exam skills and 6 procedures, and their comfort in performing 7 types of counseling, and obtaining 6 types of patient history (4 point Likert scale for each). Self-rated ability or comfort was compared by gender, status (year of residency, faculty), and future predicted frequency of use of the skill. Results: Residents reported high ability levels for physical exam skills common to both the ambulatory and hospital setting. Fewer felt able to perform musculoskeletal, neurologic or eye exams easily alone. Procedures generally received low ability ratings. Similarly, residents’ comfort in performing common outpatient counseling was also low. More residents reported feeling very comfortable in obtaining history from patients. We found little variation by gender, year of training, or predicted frequency of use. Conclusion: Self-reported ability and comfort for many common ambulatory care skills is low. Further evaluation of this finding in other training programs is warranted

Anxiety Symptoms and Immuno-endocrine Systems from Childhood to Adolescence: Understanding Reciprocal Change over Time

Anxiety symptoms may strain underlying biological systems to result in negative long-term health consequences. In addition to generating psychological distress, anxiety symptoms may affect the system’s ability to respond optimally to stress, and impede endocrine and immune functioning over time. To date, the literature shows inconsistent findings regarding the nature and directionality of the relationship between anxiety symptoms and biomarkers of the immuno-endocrine systems. To explore how different dimensions of anxiety symptoms (physiological versus cognitive-emotional) interact with and affect the underlying immuno-endocrine systems over time from childhood to adolescence, the current studies examined the following questions: (1) How and in what direction are anxiety symptoms associated with diurnal cortisol rhythms concurrently and longitudinally?; (2) Is there an association between anxiety and diurnal salivary immunoglobulin A (sIgA)?; (3) How and in what direction are anxiety symptoms related to overall sIgA levels?; and (4) Are there feedback mechanisms, whereby anxiety symptoms and immuno-endocrine biomarkers create a chain of sequential cause and effect, with each affecting the other in a transactional sequence over several years? Data were collected from participants in the Concordia Longitudinal Risk Project between the ages of 9 to 18 using a multi-wave design. Repeated measures of self-report symptom questionnaires, salivary samples of endocrine and immune biomarkers, and demographic information were collected at each data wave approximately three years apart. Hierarchical linear modeling and autoregressive cross-lagged panel designs were used to analyze the data. Results showed that higher physiological anxiety symptoms were concurrently associated with elevated diurnal cortisol, whereas longitudinal results over three years showed that chronic worry and social concerns predicted lower diurnal cortisol, illustrating a more blunted diurnal cortisol profile. Diurnal sIgA results revealed a pattern of activation in children with higher anxiety, specifically, worries and social concerns, than those with lower anxiety. Higher levels of total anxiety, worries and social concerns also led to lower levels of sIgA, which in turn led to increases in anxiety in an incremental “vicious” cycle from age 9 to 18. Taken together, these findings have important implications for understanding the developmental psychobiology of children’s anxiety

Mutational bias of Turnip Yellow Mosaic Virus in the context of host anti-viral gene silencing

Plant Dicer-like (DCL) enzymes exhibit a GC-preference during anti-viral post-transcriptional gene silencing (PTGS), delivering an evolutionary selection pressure resulting in plant viruses with GC-poor genomes. However, some viruses, e.g. Turnip Yellow Mosaic Virus (TYMV, genus Tymovirus) have GC-rich genomes, raising the question as to whether or not DCL derived selection pressure affects these viruses. In this study we analyzed the virus-derived small interfering RNAs from TYMV-infected leaves of Brassica juncea showed that the TYMV population accumulated a mutational bias with AU replacing GC (GC–AU), demonstrating PTGS pressure. Interestingly, at the highly polymorphic sites the GC–AU bias was no longer observed. This suggests the presence of an unknown mechanism preventing mutational drift of the viral population and maintaining viral genome stability, despite the host PTGS pressure

Relação entre status social subjetivo e saúde percebida entre mulheres imigrantes latino-americanas

OBJECTIVE: to explore the relationship between socioeconomic status and subjective social status and explain how subjective social status predicts health in immigrant women. METHODS: cross-sectional study based on data from 371 Latin American women (16-65 years old) from a total of 7,056 registered immigrants accesse through community parthers between 2009-2010. Socioeconomic status was measured through education, income and occupation; subjective social status was measured using the MacArthur Scale, and perceived health, using a Likert scale. RESULTS: a weak correlation between socioeconomic and subjective social status was found. In the bivariate analysis, a significantly higher prevalence of negative perceived health in women with no education, low income, undocumented employment was observed. In the multivariate analysis, higher odds of prevalence of negative perceptions of health in the lower levels of the MacArthur scale were observed. No significant differences with the rest of the variables were found. CONCLUSIONS: the study suggests that subjective social status was a better predictor of health status than the socioeconomic status measurements. Therefore, the use of this measurement may be relevant to the study of health inequalities, particularly in socially disadvantaged groups such as immigrants.OBJETIVO: explorar la relación entre el estatus socioeconómico y el estatus social subjetivo y explicar en qué medida el estatus social subjetivo predice la salud en mujeres inmigrantes. MÉTODOS: estudio transversal. Observaciones basadas en 371 latinoamericanas (16-65 años) de un total de 7.056 empadronadas, captadas a través de asociaciones entre 2009-2010. El estatus socioeconómico se midió a través de educación, ingresos y ocupación; el estatus social subjetivo usando la Escala MacArthur; y la salud percibida mediante una escala de likert. RESULTADOS: se encontró una correlación débil entre el estatus socioeconómico y el social subjetivo. En el análisis bivariante se observó significativamente una prevalencia mayor de salud percibida negativa en las mujeres sin estudios, con ingresos bajos, desempleadas e indocumentadas. En el análisis multivariante, se observaron Odds de prevalencia de salud percibida negativa más elevadas en los niveles de la escala MacArthur más bajos. No se observaron diferencias significativas con el resto de las variables. CONCLUSIONES: el estudio sugiere que el estatus social subjetivo es un predictor mejor del estado de salud que las medidas del estatus socioeconómico. Por tanto, el uso de esta medida puede ser relevante para el estudio de las desigualdades en salud, particularmente en los grupos en desventaja social como los inmigrantes.OBJETIVO: explorar a relação entre nível socieconômico e status social subjetivo e explicar como o status social subjetivo prediz a saúde em mulheres imigrantes. MÉTODOS: estudo transversal com observações baseadas em 371 mulheres latino-americanas (16-65 anos) de um total de 7.056 registradas, recrutadas por meio de parcerias entre os anos 2009 e 2010. O nível socioeconômico foi mensurado por meio de escolaridade, renda e profissão; o status social subjetivo foi mensurado utilizando-se a Escala MacArthur, e a saúde percebida, usando-se uma escala tipo Likert. RESULTADOS: encontrou-se fraca correlação entre o nível socioeconômico e o status social subjetivo. Na análise bivariada, observou-se prevalência significativamente mais alta de saúde percebida negativamente em mulheres sem escolaridade, baixa renda, desempregadas e com emprego informal. Na análise multivariada, observaram-se maiores chances de prevalência de saúde percebida negativamente, nos níveis mais baixos da escala MacArthur. Não foram encontradas diferenças significativas nas demais variáveis. CONCLUSÕES: o estudo sugere que o status social subjetivo foi um melhor preditor de status de saúde do que as mensurações de status econômico. Portanto, o uso dessa medida pode ser relevante para o estudo das desigualdades em saúde, particularmente nos grupos em desvantagem social, como os imigrantes

EXAMINATION OF THE INFLUENCE OF SELECTED FACTORS ON PERFORMANCE ON ALBERTA LEARNING ACHIEVEMENT TESTS

In this study, we identified factors that influence the academic performance of grade‐ 6 students in a large city school system in language arts and mathematics. For language arts, five student variables, seven class variables, and two school level variables accounted for approximately 50 per cent, 75 per cent, and 90 per cent of the initial variability at the corresponding levels. For mathematics, seven student, five class, and three school level variables accounted for approximately 40 per cent, 60 per cent, and 90 per cent of the initial variability at the school level. Taken together, the results reveal that the majority of variability is at the student level, and additional variables need to be identified to better explain the variability at this level. Key words: school effectiveness, hierarchical linear multi‐level modeling, large‐scale testing Dans cette étude portant sur le système scolaire d’une grande ville, les auteurs identifient les facteurs ayant une incidence sur le rendement scolaire d’élèves de 6e année en langue (anglais) et en mathématiques. Pour le domaine de la langue, cinq variables ayant trait aux élèves expliquent environ la moitié de la variabilité initiale quant aux élèves, sept variables ayant trait à la classe expliquent environ 75 % de la variabilité initiale quant aux classes et deux variables ayant trait à l’école, environ 90 % de la variabilité initiale quant aux écoles. En mathématiques, sept variables ayant trait aux élèves, cinq ayant trait aux classes et trois aux écoles expliquent respectivement environ 40 %, 60 % et 90 % de la variabilité initiale. Pris en bloc, les résultats révèlent que la majeure partie de la variabilité se situe au niveau des élèves et que d’autres variables doivent être identifiées afin de mieux expliquer la variabilité à ce niveau. Mots clés : efficacité de lʹécole, régression hiérarchique multiple, tests communs.

Behavioral responses of wild rodents to owl calls in an austral temperate forest

Ecologically based rodent management strategies are arising as a sustainable approach to rodent control, allowing us to preserve biodiversity while safeguarding human economic activities. Despite predator signals being known to generally repel rodents, few field-based studies have compared the behavioral effects of several predators on different prey species, especially in Neotropical ecosystems. Here, we used camera traps to study the behavior of rodent species native to the Chilean temperate forest (Abrothrix spp., long-tailed pygmy rice rat Oligoryzomys longicaudatus) and an introduced rodent (black rat Rattus rattus). Using playbacks of raptor calls, we experimentally exposed rodents to three predation risk treatments: austral pygmy owl calls (Glaucidium nana), rufous-legged owl calls (Strix rufipes) and a control treatment (absence of owl calls). We evaluated the effects of the treatments on the time allocated to three behaviors: feeding time, locomotor activity and vigilance. Moonlight and vegetation cover were also considered in the analyses, as they can modify perceived predation risk. Results showed that predator calls and environmental factors modified prey behavior depending not only on the predator species, but also on the rodent species. Consequently, owl playbacks could be regarded as a promising rodent control tool, knowing that future studies would be critical to deeply understand differences between species in order to select the most effective predator cues

Qualitative trends in library & information science (LIS) research

Background Over the past two decades, theorists have noted an increase in the use of qualitative research methods within library and information science (LIS). However, no recent study has sought to provide rigorous evidence of this increase. This ongoing study seeks to address two research questions: 1. How widespread is the use of qualitative data collection and analysis methods in the recent LIS research literature? 2. What are some common themes and trends within the body of recent LIS studies that have used qualitative methods? Data Collection The researchers mined the Web of Science database for abstracts from the top four LIS research journals for the period 2001-2006. Next, they designed an automated program to search the resulting pool of abstracts for set of 14 keywords. Manual analysis was then used to remove false drops. Data Analysis The study includes two data analysis stages. For Stage 1, the researchers used statistical methods to generate a quantitative snapshot of the data. The study is currently in Stage 2, which entails the use of qualitative data analysis techniques to search for themes and patterns within the pool of abstracts. Expected Findings The quantitative results will provide concrete evidence of the frequency of qualitative research methods within these top-ranked LIS research journals. The qualitative analysis will point to possible trends within LIS studies that use qualitative methods, such as dominant data collection or data analysis methods. Together, these results will help to provide a better understanding of the current face of LIS research