Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.     

MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder

Hypomorphic mutations of the MRE11 gene are the hallmark of the radiosensitive ataxia-telangiectasia-like disorder (ATLD). Here, we describe a new family with two affected siblings, ATLD5 and ATLD6, now aged 37 and 36, respectively. They presented with late onset cerebellar degeneration slowly progressing until puberty and absence of telangiectasias, and were cancer-free. Both patients were wild-type for ATM and NBS1, but compound heterozygotes for MRE11 gene mutations [1422C-->A, T481K; 1714C-->T, R571X]. The 1422C-->A allele was inherited from the mother, whereas the 1714C-->T, allele paternally inherited, was apparently null as a result of nonsense-mediated mRNA decay (NMD). Interestingly, the 1714C-->T mutation is the same as previously identified in an unrelated English ATLD family (probands ATLD3 and ATLD4), suggesting an important role for NMD in saving potentially lethal mutations. Lymphoblastoid cell lines (LCLs) derived from ATLD5 and ATLD6 were normal for ATM, but defective for Mre11, Rad50 and Nbs1 (the MRN complex) protein expression. Their response to gamma-radiation was abnormal, as evidenced by the enhanced radiosensitivity, attenuated autophosphorylation of ATM-S1981 and phosphorylation of the ATM targets p53-S15 and Smc1-S966, failure to form Mre11 nuclear foci and defective G1 checkpoint arrest. The fibroblasts, but not LCLs, from ATLD5 and ATLD6 showed an impaired ATM-dependent Chk2 phosphorylation. These findings further underscore the interconnection between ATM activity and MRN function, which rationalizes the clinical similarity between ataxia-telangiectasia (A-T) and ATLD.     

Building a Methodological Foundation for Impactful Urban Planetary Health Science

Anthropogenic environmental change will heavily impact cities, yet associated health risks will depend significantly on decisions made by urban leaders across a wide range of non-health sectors, including transport, energy, housing, basic urban services, and others. A subset of planetary health researchers focus on understanding the urban health impacts of global environmental change, and how these vary globally and within cities. Such researchers increasingly adopt collaborative transdisciplinary approaches to engage policy-makers, private citizens, and other actors in identifying and evaluating potential policy solutions that will reduce environmental impacts in ways that simultaneously promote health, equity, and/or local economies—in other words, maximising ‘co-benefits’. This report presents observations from a participatory workshop focused on challenges and opportunities for urban planetary health research. The workshop, held at the 16th International Conference on Urban Health (ICUH) in Xiamen, China, in November 2019, brought together 49 participants and covered topics related to collaboration, data, and research impact. It featured research projects funded by the Wellcome Trust’s Our Planet Our Health (OPOH) programme. This report aims to concisely summarise and disseminate participants’ collective contributions to current methodological practice in urban planetary health research.     

Loops and Building Blocks: a Knowledge co-Production Framework for Equitable Urban Health

This paper sets out a structured process for the co-production of knowledge between researchers and societal partners and illustrates its application in an urban health equity project in Accra, Ghana. The main insight of this approach is that research and knowledge co-production is always partial, both in the sense of being incomplete, as well as being circumscribed by the interests of participating researchers and societal partners. A second insight is that project-bound societal engagement takes place in a broader context of public and policy debate. The approach to co-production described here is formed of three recursive processes: co-designing, co-analysing, and co-creating knowledge. These ‘co-production loops’ are themselves iterative, each representing a stage of knowledge production. Each loop is operationalized through a series of research and engagement practices, which we call building blocks. Building blocks are activities and interaction-based methods aimed at bringing together a range of participants involved in joint knowledge production. In practice, recursive iterations within loops may be limited due of constraints on time, resources, or attention. We suggest that co-production loops and building blocks are deployed flexibly.     

Exposure to psychosocial work strain and changes in smoking behavior during pregnancy – a longitudinal study within the Danish National Birth Cohort

Objective:Knowledge of the relationship between psychosocial strain in the work environment and smoking during pregnancy is scarce. This study aimed to examine the association between psychosocial job strain and change in smoking behavior during pregnancy.Methods:The cohort included 65 645 pregnancies from the Danish National Birth Cohort (1996–2002), where pregnant women were interviewed on job factors and lifestyle during the first and third trimesters. Smoking was categorized into non-, non-daily, and daily smoking at each interview. Psychosocial job strain was categorized into four groups based on the concept of Karasek’s demand–control model: low strain (reference), passive, active and high strain. Associations between psychosocial strain and change in smoking status between the first and second interviews were analyzed by multinomial logistic regression, separately for each smoking category at first interview.Results:Non-smoking women exposed to high strain work were more likely to become daily smokers [adjusted odds ratio (OR_adj) 1.41, (95% confidence interval (CI) 1.08–1.83)] compared to non-smoking women exposed to low strain work. Non-smoking women exposed to passive work were more likely to become both non-daily and daily smokers [OR_adj 1.59 (95% CI 1.21–2.08) and OR_adj 1.32 (95% CI 1.03–1.70), respectively]. Daily smoking women exposed to high strain work were less likely to decrease their smoking [OR_adj 0.57 (95% CI 0.32–0.99)] compared to daily smoking women exposed to low strain work.Conclusions:Psychosocial strain influenced the women’s smoking behavior during pregnancy, especially in job types with low control.     

Association between food patterns and difficulties in falling asleep among adolescents in Norway — a descriptive Young-Hunt3 study

Journal of Public Health - Adolescents’ sleep duration has decreased over the past century; this is mainly caused by problems with falling asleep. Short sleep duration, poor sleep quality,...     

UV-Cured PDMS for Oil Removal from Wastewater

The removal of oil from water is a worldwide challenge that must be faced to avoid irreversible marine habitat destruction. A novel fast and simple technique to obtain polydimethylsiloxane (PDMS) membranes is developed using the photopolymerization technique. The high reactivity of the acrylated PDMS formulation toward photo-induced free radical polymerization is assessed via the differential scanning photo-calorimetry (photo-DSC) technique. Two different membranes dense or porous are developed and investigated. Porous membranes, having 100–200 µm as pore size, are obtained using a low-cost environmentally friendly sodium chloride template. Thanks to the hydrophobic/oleophilic intrinsic characteristic of PDMS, the UV-cured membranes can selectively remove dodecane, selected as the target oil, from water. The dodecane sorption capability of both membranes is investigated and compared. Moreover, the membranes can be easily reused since the adsorbed oil can be recovered by simply compressing the membrane. Those PDMS sorbents show high mechanical stability after five adsorption/desorption cycles.     

Increased proportions of B cells with spontaneous production of interleukin‐10 in HIV‐infected individuals are normalized during combination antiretroviral therapy: a longitudinal study

Interleukin‐10 (IL‐10)‐producing B cells (B10 cells) may inhibit HIV‐specific T cells and are elevated in untreated HIV infection. We aimed to determine the effect of combination antiretroviral treatment (cART) on the proportion of B10 cells. Furthermore, we compared B10‐cell proportions in HIV‐infected progressors and viremic controllers. This was a prospective study including HIV‐infected progressors, viremic controllers and healthy controls. Progressors initiating cART were followed for 6 months. Purified B cells were stimulated with CpG, alone or in combination with HIV gp120, and the proportion of B10 cells was measured by flow cytometry. Without stimulation, the B10‐cell proportion was higher in progressors than in healthy controls, while viremic controllers and healthy controls had comparable proportions. Moreover, the proportion of CD24^hiCD38^hi transitional B cells was higher in progressors than in healthy controls. After initiation of cART, the proportion of B10 cells and transitional B cells decreased. In conclusion, progressors had elevated B10‐cell proportions, while viremic controllers displayed normal proportions. After initiation of cART, the B10‐cell proportion decreased. This could limit B10‐cell‐mediated suppression of specific CD8⁺ T‐cell responses.