Family Trouble: Heteronormativity, emotion work and queer youth mental health

Conflict with the family about sexual orientation and gender diversity is a key risk factor associated with poor mental health in youth populations. Findings presented here derive from a UK study that employed an interdisciplinary critical mental health approach that de-pathologized emotional distress and conceptualised families as social and affective units that are created through everyday practices. Our aim was to explore how family relationships foster, maintain or harm the mental health and wellbeing of LGBTQ+ youth. Data were generated through exploratory visual, creative and digital qualitative methods in two phases. Phase 1 involved digital/paper emotion maps and interviews with LGBTQ+ youth aged 16-25 (n=12) and family member/mentor interviews (n=7). Phase 2 employed diary methods and follow-up interviews (n=9). The data analytic strategy involved three stages: individual case analysis; cross-sectional thematic analysis; and metainterpretation. We found that family relationships impacted on queer youth mental health in complex ways that were related to the establishment of their autonomous queer selves, the desire to remain belonging to their family and the need to maintain a secure environment. The emotion work involved in navigating identity, belonging and security was made difficult because of family heteronormativity, youth autonomy and family expectations and had a stark impact on queer youth mental health and wellbeing. Improving the mental health of LGBTQ+ youth requires a much deeper understanding of the emotionality of family relationships and the difficulties negotiating these as a young person

The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression

Background: Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer

<em>NUDCD3</em> deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome

Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 (NUDCD3). Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T -B- SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1