Social capital and HIV-serodiscordance: Disparities in access to personal and professional resources for HIV-positive and HIV-negative partners.

As people living with HIV are living longer lives, they have a correspondingly greater opportunity to enjoy long-term romantic and sexual partnerships, including with persons who do not live with HIV ("serodiscordant" relationships). In these dyads, asymmetries may emerge in access to social resources between partners. In this paper we examined how serodiscordant couples access informal (interpersonal, such as family and friends) and formal (practitioner, such as doctor or social worker) social resources for health. We recruited 540 participants in current serodiscordant relationships, working with 150 AIDS service organizations and HIV clinics across Canada from 2016 to 2018. Our findings demonstrate that partners with HIV have greater access to formal resources than their partners (through health care professionals, therapists/counselors/support workers), while both persons have similar access to resources through informal social relationships (family and friends). Furthermore, the findings indicated that HIV positive partners accessed more varied forms of support through formal ties, compared to HIV negative persons. We offer recommendations for changes to how HIV-negative partners in a serodiscordant relationship are served and cared for, and particularly, the importance of moving toward dyad-focused policies and practices

Innovation and Access to Technologies for Sustainable Development: A Global Systems Perspective

This workshop report is a summary of themes discussed by five panels during a daylong workshop on “Innovation and Access to Technologies for Sustainable Development: A Global Perspective” at Harvard University on April 24,2014. The workshop brought together a diverse group of scholars to explore how the technological innovation needed for sustainable development can be promoted in ways that assure equitable access in current and future generations. Three key themes that emerged from the workshop include:(1) The central role of power, politics and agency in analyzing technological innovation and sustainable development -an important aspect of this includes the articulation of the roles of actors and organizations within frameworks and models of innovation systems.(2) The importance of focusing both on supply-push and demand-pull mechanisms in innovation scholarship and innovation policy.(3) The need to focus on more innovation scholarship around the goals of sustainable development

A national recruitment strategy for HIV-serodiscordant partners living in Canada for the Positive Plus One study: a mixed-methods study.

BACKGROUND: With the recent shift in focus to addressing HIV risk within relationships and couple-based interventions to prevent HIV transmission, successful recruitment of individuals involved in HIV-serodiscordant relationships is crucial. This paper evaluates methods used by the Positive Plus One (PP1) study to recruit and collect data on a diverse national sample of dyads and individuals involved in current or past HIV-serodiscordant relationships, discusses the strengths and limitations of the recruitment approach, and makes recommendations to inform the interpretation of study results and the design of future studies. METHODS: PP1 used a multi-pronged approach to recruit adults involved in a current or past HIV-serodiscordant relationship in Canada from 2016 to 2018 to complete a survey and an interview. Upon survey completion, index (first recruited) partners were invited to recruit their primary current HIV-serodiscordant partner. We investigated participant enrollment by recruitment source, participant-, relationship-, and dyad-level sociodemographic characteristics, missing data, and correlates of participation for individuals recruited by their partners. RESULTS: We recruited 613 participants (355 HIV-positive; 258 HIV-negative) across 10 Canadian provinces, including 153 complete dyads and 307 individuals who participated alone, and representing 460 HIV-serodiscordant relationships. Among those in current relationships, HIV-positive participants were more likely than HIV-negative participants to learn of the study through an ASO staff member (36% v. 20%, p < 0.001), ASO listserv/newsletter (12% v. 5%, p = 0.007), or physician/staff at a clinic (20% v. 11%, p = 0.006). HIV-negative participants involved in current relationships were more likely than HIV-positive participants to learn of the study through their partner (46% v. 8%, p < 0.001). Seventy-eight percent of index participants invited their primary HIV-serodiscordant partner to participate, and 40% were successful. Successful recruitment of primary partners was associated with longer relationship duration, higher relationship satisfaction, and a virally suppressed HIV-positive partner. CONCLUSIONS: Our findings provide important new information on and support the use of a multi-pronged approach to recruit HIV-positive and HIV-negative individuals involved in HIV-serodiscordant relationships in Canada. More creative strategies are needed to help index partners recruit their partner in relationships with lower satisfaction and shorter duration and further minimize the risk of "happy couple" bias

Assessing the ecological risks from the persistence and spread of feral populations of insect-resistant transgenic maize

One source of potential harm from the cultivation of transgenic crops is their dispersal, persistence and spread in non-agricultural land. Ecological damage may result from such spread if the abundance of valued species is reduced. The ability of a plant to spread in non-agricultural habitats is called its invasiveness potential. The risks posed by the invasiveness potential of transgenic crops are assessed by comparing in agronomic field trials the phenotypes of the crops with the phenotypes of genetically similar non-transgenic crops known to have low invasiveness potential. If the transgenic and non-transgenic crops are similar in traits believed to control invasiveness potential, it may be concluded that the transgenic crop has low invasiveness potential and poses negligible ecological risk via persistence and spread in non-agricultural habitats. If the phenotype of the transgenic crop is outside the range of the non-transgenic comparators for the traits controlling invasiveness potential, or if the comparative approach is regarded as inadequate for reasons of risk perception or risk communication, experiments that simulate the dispersal of the crop into non-agricultural habitats may be necessary. We describe such an experiment for several commercial insect-resistant transgenic maize events in conditions similar to those found in maize-growing regions of Mexico. As expected from comparative risk assessments, the transgenic maize was found to behave similarly to non-transgenic maize and to be non-invasive. The value of this experiment in assessing and communicating the negligible ecological risk posed by the low invasiveness potential of insect-resistant transgenic maize in Mexico is discussed

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylati

Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals

Funding Information: The study was supported by the European Regional Development Fund under the project ?Investigation of interplay between multiple determinants influencing response to metformin: search for reliable predictors for efficacy of type 2 diabetes therapy? (Project No.: 1.1.1.1/16/A/091, https://ec.europa.eu/regional_policy/en/funding/ erdf/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all the volunteers for their participation and acknowledge the Genome Database of the Latvian Population for providing biological material and data. Publisher Copyright: © 2019 Ustinova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes mellitus. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed metformin-induced differential expression of genes involved in intestinal immune network for IgA production and cytokine-cytokine receptor interaction pathways. Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin’s action. In addition to universal effects, 4 clusters of functionally related genes with a subject-specific differential expression were distinguished, including genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). This inter-individual variation of the metformin effect on the transcriptional regulation goes in line with well-known variability of the therapeutic response to the drug.publishersversionPeer reviewe

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals