Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation

Cranial radiotherapy in children often leads to progressive cognitive decline. We have established a rodent model of irradiation-induced injury to the young brain. A single dose of 8 Gy was administered to the left hemisphere of postnatal day 10 (P10) mice. Harlequin (Hq) mice, carrying the hypomorphic apoptosis-inducing factor AIFHq mutation, express 60% less AIF at P10 and displayed significantly fewer dying cells in the subventricular zone (SVZ) 6 h after IR, compared with wild type (Wt) littermates. Irradiated cyclophilin A-deficient (CypA−/−) mice confirmed that CypA has an essential role in AIF-induced apoptosis after IR. Hq mice displayed no reduction in SVZ size 7 days after IR, whereas 48% of the SVZ was lost in Wt mice. The proliferation rate was lower in the SVZ of Hq mice. Cultured neural precursor cells from the SVZ of Hq mice displayed a slower proliferation rate and were more resistant to IR. IR preferentially kills proliferating cells, and the slower proliferation rate in the SVZ of Hq mice may, at least partly, explain the protective effect of the Hq mutation. Together, these results indicate that targeting AIF may provide a fruitful strategy for protection of normal brain tissue against the detrimental side effects of IR

VHL Type 2B Mutations Retain VBC Complex Form and Function

Background: von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1a and HIF-2a), resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. Methodology/Principal Findings: This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1a. Conclusions: Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition fo

‘Everyday bordering’ in England, Sweden and Bulgaria: Social work decision-making processes when working with migrant family members

The global movement of people is a growing feature of contemporary life, and it is essential that professionals providing support services know how to best engage with migrant families. However, despite globalisation and the related processes of de-bordering, borders continue to remain significant and, in contemporary life, the ways in which immigration is controlled and surveilled—bureaucratically and symbolically—are multiple. The paper draws on data gathered in the immediate period following the so called 2015 European ‘migration crisis’ and examines whether and in what ways social workers in three European countries—Bulgaria, Sweden and England—enact bordering in their work with migrant family members. We apply the concept of ‘everyday bordering’ to the data set: whilst borders are traditionally physical and at the boundary between nation states, bordering practices increasingly permeate everyday life in bureaucratic and symbolic forms. Overall, the data show that everyday bordering affects social work practice in three ways: by social workers being required to engage in bordering as an everyday practice; by producing conditions that require social workers to negotiate borders; and in revealing aspects of symbolic everyday bordering. Our analyses shows that ‘everyday bordering’ practices are present in social work decision-making processes in each country, but the forms they take vary across contexts. Analysis also indicates that, in each country, social workers recognise the ways in which immigration control can impact on the families with whom they work but that they can also inadvertently contribute to the ‘othering’ of migrant populations

Examination of bidirectional relationships between fear of negative evaluation and weight/shape concerns over 3 years: A longitudinal cohort study of Australian adolescents

OBJECTIVE: Adolescents commonly experience both fear of negative evaluation and weight/shape concerns. However, evidence concerning the prospective associations between these constructs during adolescence is limited. The current study examined the bidirectional relationships between fear of negative evaluation and weight/shape concerns over a 3-year period in adolescents. METHOD: Australian high school students (n = 2073; 55% girls) completed self-report measures at three timepoints, each 1 year apart. RESULTS: Findings showed a bidirectional relationship, whereby increases in fear of negative evaluation predicted exacerbated weight/shape concerns, and vice versa. Results point towards a vicious maintenance cycle between fear of negative evaluation and weight/shape concerns. DISCUSSION: Findings from the current study highlight the importance of considering both fear of negative evaluation and weight/shape concerns in the development of health promotion and prevention programs designed to reduce the occurrence and adverse effects of body dissatisfaction or improve general mental health. PUBLIC SIGNIFICANCE: Many adolescents experience some level of fear of negative evaluation (i.e., worry about being judged by others) and worry about their weight and/or shape. This study examined the prospective relationship between both constructs. Findings showed a bidirectional relationship, whereby higher fear of negative evaluation predicted increased weight/shape concerns, and vice versa. Programs designed to reduce body dissatisfaction might be improved by targeting both fear of negative evaluation and weight/shape concerns