Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism

Community Engagement, Trust, and Genetic Testing for Inherited Diseases Among Adopted Persons

We identify concerns pertinent to establishing trust necessary to support adoptees’ confidence in and uptake of genetic testing that might allow them to benefit from early screening and medical intervention. Using principles of community-based participatory research, our study sought to build a foundation of trust to document such perspectives. Three focus groups were held with 12 adult adoptees. Transcripts were analyzed using thematic content analysis. Comments highlighted aspects related to genomics and health history in the context of adoption, specifically: (1) trust in the intention of the research study; (2) trust that the adoption community will benefit from the results of research; and (3) trust in the protection from misuse and abuse of genomic data. Results reinforce the call for proper security of data and oversight of the ways it is used and point to the value of including researchers who are a part of the community under study

Health and Historical Levels of Freedom

Background: The link between political freedom and health is unclear. We aimed to determine the association byexploring the relationship of historical and cumulative freedom levels with important health outcomes. Methods: We obtained countrywide health indicators for life expectancy, infant mortality, maternal mortality ratio, %low birth weight babies, Gini coefficient (a measure of wealth inequality) and various markers of freedom based onpolitical rights and civil liberties. We applied multivariable logistic regression to examine the association betweenhealth indicators and within-country years of freedom as determined by Freedom House rankings. Results: The total proportion of free years from 1972-2005, the duration of current freedom level, and the Ginicoefficient show independent positive associations with health indicators, which remain after the adjustment fornational wealth, total government expenditure, and spending on health. Countries identified as having high totalproportion of free years demonstrated significantly better health outcomes than countries with low levels of freedom(life expectancy, Odds Ratio [OR] 7.2, 95% Confidence Interval [CI], 2.3-22.6, infant mortality OR 19.6, 95% CI, 5.6-67.7,maternal mortality ratio, OR 24.3, 95% CI, 6.2-94.9, and % low birth weight babies OR 3.8, 95% CI, 1.4-10.8). This was alsothe case for infant mortality (OR 3.4, 95% CI, 1.0-8.4), maternal mortality ratio (OR 4.0, 95% CI, 1.2-12.8), and % low birthweight babies (OR 2.6, 95% CI, 1.0-6.6) among countries considered as having medium levels of freedom. Interpretation: We found strong associations between country-level freedom and important health outcomes. Thecumulative level of freedom over time shows stronger associations with all health indicators than the duration ofcurrent freedom level

Sequence verification of synthetic DNA by assembly of sequencing reads

Gene synthesis attempts to assemble user-defined DNA sequences with base-level precision. Verifying the sequences of construction intermediates and the final product of a gene synthesis project is a critical part of the workflow, yet one that has received the least attention. Sequence validation is equally important for other kinds of curated clone collections. Ensuring that the physical sequence of a clone matches its published sequence is a common quality control step performed at least once over the course of a research project. GenoREAD is a web-based application that breaks the sequence verification process into two steps: the assembly of sequencing reads and the alignment of the resulting contig with a reference sequence. GenoREAD can determine if a clone matches its reference sequence. Its sophisticated reporting features help identify and troubleshoot problems that arise during the sequence verification process. GenoREAD has been experimentally validated on thousands of gene-sized constructs from an ORFeome project, and on longer sequences including whole plasmids and synthetic chromosomes. Comparing GenoREAD results with those from manual analysis of the sequencing data demonstrates that GenoREAD tends to be conservative in its diagnostic. GenoREAD is available at www.genoread.or

Health and historical levels of freedom

<p>Abstract</p> <p>Background</p> <p>The link between political freedom and health is unclear. We aimed to determine the association by exploring the relationship of historical and cumulative freedom levels with important health outcomes.</p> <p>Methods</p> <p>We obtained countrywide health indicators for life expectancy, infant mortality, maternal mortality ratio, % low birth weight babies, Gini coefficient (a measure of wealth inequality) and various markers of freedom based on political rights and civil liberties. We applied multivariable logistic regression to examine the association between health indicators and within-country years of freedom as determined by Freedom House rankings.</p> <p>Results</p> <p>The total proportion of free years from 1972-2005, the duration of current freedom level, and the Gini coefficient show independent positive associations with health indicators, which remain after the adjustment for national wealth, total government expenditure, and spending on health. Countries identified as having high total proportion of free years demonstrated significantly better health outcomes than countries with low levels of freedom (life expectancy, Odds Ratio [OR] 7.2, 95% Confidence Interval [CI], 2.3-22.6, infant mortality OR 19.6, 95% CI, 5.6-67.7, maternal mortality ratio, OR 24.3, 95% CI, 6.2-94.9, and % low birth weight babies OR 3.8, 95% CI, 1.4-10.8). This was also the case for infant mortality (OR 3.4, 95% CI, 1.0-8.4), maternal mortality ratio (OR 4.0, 95% CI, 1.2-12.8), and % low birth weight babies (OR 2.6, 95% CI, 1.0-6.6) among countries considered as having medium levels of freedom.</p> <p>Interpretation</p> <p>We found strong associations between country-level freedom and important health outcomes. The cumulative level of freedom over time shows stronger associations with all health indicators than the duration of current freedom level.</p

Fitness, PA, Perceived Competence, Parental Support, and Literacy Outcomes in the REACH After-School Sports Program

The purpose of this study was to assess the effectiveness of the REACH program in increasing physical activity (PA) levels, cardiorespiratory fitness, perceived competence, self-efficacy, parental support, and literacy across a year-long after-school PA intervention. Participants (N = 78) were students who volunteered from after-school program at either one of the two intervention schools or the control schools. Data are presented from two time points: Baseline (Aug/Sep 2017), and Post (end of the school year in May 2018). Data consisted of PA levels measured by PAC-Q, PACER test, Harter’s Perceived Competence questionnaire, parental support, and literacy tests. School differences in post-intervention scores were found in three (parental support, literacy, PACER) of seven intervention-related measures. Most notably parental support was higher in intervention schools over the control and PACER scores were higher in one intervention school than the control. The results demonstrate that data collection methods may need to be reconsidered in diverse low-income schools. The dramatic amount of missing data and lack of student effort points to students perhaps being overwhelmed with standardized tests and performing tasks for researchers. This leads to a dilemma in data collection in after-school programs in low-income schools: researchers need data to understand what is happening but how are students being served by the data collection process? Researchers should consider new approaches to collect data in low-income urban after-school programs to limit loss of data and to make the data collection meaningful to student participants

Establishing the values for patient engagement (PE) in health-related quality of life (HRQoL) research: an international, multiple-stakeholder perspective

PurposeActive patient engagement is increasingly viewed as essential to ensuring that patient-driven perspectives are considered throughout the research process. However, guidance for patient engagement (PE) in HRQoL research does not exist, the evidence-base for practice is limited, and we know relatively little about underpinning values that can impact on PE practice. This is the first study to explore the values that should underpin PE in contemporary HRQoL research to help inform future good practice guidance. MethodsA modified ‘World Café’ was hosted as a collaborative activity between patient partners, clinicians and researchers: self-nominated conference delegates participated in group discussions to explore values associated with the conduct and consequences of PE. Values were captured via post-it notes and by nominated note-takers. Data were thematically analysed: emergent themes were coded and agreement checked. Association between emergent themes, values and the Public Involvement Impact Assessment Framework were explored. ResultsEighty participants, including 12 patient partners, participated in the 90-min event. Three core values were defined: (1) building relationships; (2) improving research quality and impact; and (3) developing best practice. Participants valued the importance of building genuine, collaborative and deliberative relationships—underpinned by honesty, respect, co-learning and equity—and the impact of effective PE on research quality and relevance. Conclusions An explicit statement of values seeks to align all stakeholders on the purpose, practice and credibility of PE activities. An innovative, flexible and transparent research environment was valued as essential to developing a trustworthy evidence-base with which to underpin future guidance for good PE practice.Peer reviewe

Understanding the links between resilience and type-2 diabetes self-management: a qualitative study in South Australia

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Research conducted by Ward, Muller, Tsourtos, et al. (Soc Sci Med 72(7):1140–1148, 2011) has led to the development of the psycho-social interactive model of resilience, which reveals the interaction between individual resilience factors (i.e. coping, confidence and self esteem) and external resilience environments (i.e. employment, supportive family environments and health promoting policies) in facilitating the development of resilience. This present study explored the utility of this model of resilience for understanding how people self-manage type-2 diabetes. Methods Data were collected via 14 semi-structured life-history interviews with women and men living with type-2 diabetes mellitus (T2DM). Participants varied according to socio-demographics (gender, age, education level, income) and were recruited based on their self-reported management (or lack thereof) of T2DM. Results The inter-play of internal traits and external resources with additive and subtractive resilience strategies were consistent with the psycho-social interactive model of resilience. Self-management was influenced by life history. Differences in self-management and material disadvantage were also identified. Alongside increased disadvantage are higher levels of external barriers to self-management practices. Conclusions This paper supports the concepts of additive and subtractive resilience strategies for use with diabetes populations; providing health professionals and policy makers with an increased understanding of how to recognize and foster patient resilience for the improvement of self-care, disease management and ultimately health outcomes

Structure and spectroscopy of CuH prepared via borohydride reduction

Copper(I) hydride (cuprous hydride, CuH) was the first binary metal hydride to be discovered (in 1844) and is singular in that it is synthesized in solution, at ambient temperature. There are several synthetic paths to CuH, one of which involves reduction of an aqueous solution of CuSO(4)·5H(2)O by borohydride ions. The product from this procedure has not been extensively characterized. Using a combination of diffraction methods (X-ray and neutron) and inelastic neutron scattering spectroscopy, we show that the CuH from the borohydride route has the same bulk structure as CuH produced by other routes. Our work shows that the product consists of a core of CuH with a shell of water and that this may be largely replaced by ethanol. This offers the possibility of modifying the properties of CuH produced by aqueous routes

Corneal Decellularization: A Method of Recycling Unsuitable Donor Tissue for Clinical Translation?

Background: There is a clinical need for biomimetic corneas that are as effective, preferably superior, to cadaveric donor tissue. Decellularized tissues are advantageous compared to synthetic or semi-synthetic engineered tissues in that the native matrix ultrastructure and intrinsic biological cues including growth factors, cytokines and glycosaminoglycans may be retained. However, there is currently no reliable, standardized human corneal decellularization protocol.Methods: Corneal eye-bank tissue unsuitable for transplantation was utilized to systematically compare commonly used decellularization protocols. Hypertonic sodium chloride; an ionic reagent, sodium dodecyl sulphate; a non-ionic detergent, tert-octylphenol polyoxyethylene (Triton-X); enzymatic disaggregation using Dispase; mechanical agitation; and the use of nucleases were investigated. Decellularization efficacy, specifically for human corneal tissue, was extensively evaluated. Removal of detectable cellular material was evidenced by histological, immunofluorescence and biochemical assays. Preservation of macroscopic tissue transparency and light transmittance was evaluated. Retention of corneal architecture, collagen and glycosaminoglycans was assessed via histological, immunofluorescence and quantitative analysis. Biocompatibility of the resulting scaffolds was assessed using cell proliferation assays.Results: None of the decellularization protocols investigated successfully removed 100% of cellular components. The techniques with the least residual cellular material were most structurally compromised. Biochemical analysis of glycosaminoglycans demonstrated the stripping effects of the decellularization procedures.Conclusion: The ability to utilize, reprocess and regenerate tissues deemed “unsuitable” for transplantation allows us to salvage valuable tissue. Reprocessing the tissue has the potential to have a considerable impact on addressing the problems associated with cadaveric donor shortage. Patients would directly benefit by accessing greater numbers of corneal grafts and health authorities would fulfill their responsibility for the delivery of effective corneal reconstruction to alleviate corneal blindness. However, in order to progress, we may need to take a step back to establish a “decellularization” criterion; which should balance effective removal of immune reactive material with maintenance of tissue functionality