Drosophila melanogaster P-glycoprotein : A membrane detoxification system toward polycyclic aromatic hydrocarbon pollutants

International audiencePolycyclic aromatic hydrocarbons (PAHs) are well-known ubiquitous environmental contaminants. Permeability glycoprotein (P-gp) is a transmembrane detoxification efflux pump transporting various lipophilic xenobiotics, such as PAHs, out of the cells. The existence of a P-gp detoxification system inducible by PAHs was investigated in Drosophila melanogaster. Western blot experiments showed that D. melanogaster expressed a 140-kDa P-gp in S12 cells, embryos, and adult flies. Permeability glycoprotein was expressed in adult flies in the head, abdomen, and thorax and sublocalized in the sexual and olfactory organs. Flow cytometry experiments using Drosophila S12 cells in the presence of PAHs and target P-gp drug compounds revealed that Drosophila P-gp acted as an efflux detoxification pump. In Drosophila exposed to benzo[a]pyrene or to ambient air polluted by higher or lower PAH concentrations, P-gp expression was clearly showed a dose-dependent increase response. The P-gp induction was detected both in adult flies and in different fly parts, such as the head, thorax, and antennae. Drosophila P-gp acts as a membrane barrier against PAH pollutants

Mapping perceptions of species' threats and population trends to inform conservation efforts: the Bornean orangutan case study

AIM: We demonstrate a robust approach for predicting and mapping threats and population trends of wildlife species, invaluable for understanding where to target conservation resources. We used the endangered Bornean orangutan (Pongo pygmaeus) as our case study to facilitate and strengthen conservation efforts by the Indonesian government to stabilize populations by 2017. LOCATION: Kalimantan, Indonesian Borneo. METHODS: Local knowledge of threats to orangutan populations was gathered through questionnaire interviews in 531 villages (512 in Kalimantan) within known orangutan range. These data were integrated with 39 environmental/socio-economic spatial variables using boosted regression tree modelling to predict threat levels and population trends across Kalimantan and to identify key combinations of threats and trends that can help to direct appropriate conservation actions. RESULTS: Nineteen percentage of villages surveyed in Kalimantan reported human-orangutan conflicts. High-predicted conflict likelihood was extensive, strongly associated with road density (very low or high) and temperature seasonality. Recent orangutan killings were reported in 23% of villages. High killing risk was highly associated with greater surrounding orangutan habitat and for villages more than 60 km from oil palm plantations. Killings by respondents were reported in 20% of villages with higher likelihoods associated with greater range in rainfall and temperature, and higher proportion of Christian believers. Orangutan populations were predicted to decline/become locally extinct across the majority of their range in Kalimantan over the next decade, with few regions predicted to support stable populations. MAIN CONCLUSIONS: Human-orangutan conflicts and killings occur extensively in Kalimantan, with many populations at risk of decline or localized extinctions. Effective conservation actions are therefore urgently needed. Our approach better informs conservation managers in understanding the extent, spatial patterns and drivers of threats to endangered species such as the orangutan. This is essential to better design management strategies that can minimize or avert the species' decline

Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

International audienceTo the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency

International audiencePURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles.METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included.RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04).CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

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