Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation

BRCA1 plays an important role in mechanisms of response to double-strand breaks, participating in genome surveillance, DNA repair, and cell cycle checkpoint arrests. Here, we identify a constitutive BRCA1-c-Abl complex and provide evidence for a direct interaction between the PXXP motif in the C terminus of BRCA1 and the SH3 domain of c-Abl. Following exposure to ionizing radiation (IR), the BRCA1-c-Abl complex is disrupted in an ATM-dependent manner, which correlates temporally with ATM-dependent phosphorylation of BRCA1 and ATM-dependent enhancement of the tyrosine kinase activity of c-Abl. The BRCA1-c-Abl interaction is affected by radiation-induced modification to both BRCA1 and c-Abl. We show that the C terminus of BRCA1 is phosphorylated by c-Abl in vitro. In vivo, BRCA1 is phosphorylated at tyrosine residues in an ATM-dependent, radiation-dependent manner. Tyrosine phosphorylation of BRCA1, however, is not required for the disruption of the BRCA1-c-Abl complex. BRCA1-mutated cells exhibit constitutively high c-Abl kinase activity that is not further increased on exposure to IR. We suggest a model in which BRCA1 acts in concert with ATM to regulate c-Abl tyrosine kinase activity

Respiratory distress and perinatal lethality in Nedd4-2-deficient mice

The epithelial sodium channel (ENaC) is essential for sodium homoeostasis in many epithelia. ENaC activity is required for lung fluid clearance in newborn animals and for maintenance of blood volume and blood pressure in adults. In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression. Here we show that knockout of Nedd4-2 in mice leads to increased ENaC expression and activity in embryonic lung. This increased ENaC activity is the likely reason for premature fetal lung fluid clearance in Nedd4-2−/− animals, resulting in a failure to inflate lungs and perinatal lethality. A small percentage of Nedd4-2−/− animals survive up to 22 days, and these animals also show increased ENaC expression and develop lethal sterile inflammation of the lung. Thus, we provide critical in vivo evidence that Nedd4-2 is essential for correct regulation of ENaC expression, fetal and postnatal lung function and animal survival

Global Retail Chains and Poor Farmers: Evidence from Madagascar

Global retail companies ('supfirmarkets' have an increasing influence on developing countries, through foreign investments and/or through the imposition of their private standards. The impact on developing countries and poverty is often assessed as negative. In this paper we show the opposite, based on an analysis of primary data collected to measure the impact of supfirmarkets on small contract firmers in Madagascar, one of the poorest countries in the world. Almost 10,000 firmers in the Highlands of Madagascar produce vegetables for supfirmarkets in Europe. In this global supply chain, small firmers?micro-contracts are combined with extensive firm assistance and supervision programs to fulfill complex quality requirements and phyto-sanitary standards of supfirmarkets. Small firmers that participate in these contracts have higher welfare, more income stability and shorter lean periods. We also find significant effects on improved technology adoption, better resource management and spillovers on the productivity of the staple crop rice. The small but emerging modern retail sector in Madagascar does not (yet) deliver these benefits as they do not (yet) request the same high standards for their supplies

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation

Mutations of the Serine Protease CAP1/Prss8 Lead to Reduced Embryonic Viability, Skin Defects, and Decreased ENaC Activity.

CAP1/Prss8 is a membrane-bound serine protease involved in the regulation of several different effectors, such as the epithelial sodium channel ENaC, the protease-activated receptor PAR2, the tight junction proteins, and the profilaggrin polypeptide. Recently, the V170D and the G54-P57 deletion mutations within the CAP1/Prss8 gene, identified in mouse frizzy (fr) and rat hairless (fr(CR)) animals, respectively, have been proposed to be responsible for their skin phenotypes. In the present study, we analyzed those mutations, revealing a change in the protein structure, a modification of the glycosylation state, and an overall reduction in the activation of ENaC of the two mutant proteins. In vivo analyses demonstrated that both fr and fr(CR) mutant animals present analogous reduction of embryonic viability, similar histologic aberrations at the level of the skin, and a significant decrease in the activity of ENaC in the distal colon compared with their control littermates. Hairless rats additionally had dehydration defects in skin and intestine and significant reduction in the body weight. In conclusion, we provided molecular and functional evidence that CAP1/Prss8 mutations are accountable for the defects in fr and fr(CR) animals, and we furthermore demonstrate a decreased function of the CAP1/Prss8 mutant proteins. Therefore, fr and fr(CR) animals are suitable models to investigate the consequences of CAP1/Prss8 action on its target proteins in the whole organism

Flux Des Emissions Aériennes Et De Gaz A Effet De Serre Du Charbon De Bois Par La Méthode d’Analyse De Cycle De Vie

The charcoal is a solid fuel mainly used for Malagasy household cooking.  Greenhouse gases and other gases are emitted during the carbonization, transporting and cooking. The aim of this study is to quantify air emissions and greenhouse gases of charcoal. Life Cycle Assessment is adopted for this study since wood exploitation to charcoal utilization and 1MJ of useful energy from charcoal is taken as functional unit. This paper shows 763,08.10-6 éq SO2/FU  of air emissions, 1,74 kg éq CO2/FU of  greenhouse gases emissions and  75% of these are from charcoal manufacturing especially the carbonization

Suivi et analyse des succès et des abandons des systèmes à base de semis direct sous couverture végétale (SCV), mise au point de la méthodologie. Cas du Fonkontany d'Antsapanimahazo (Madagascar) : document de travail BV lac n 3, BVPI/SCRID/FOFIFA/TAFA. Montpellier, CIRAD

Document de travai

Potentiels d’Acidification Et De Réchauffement Climatique Des Bois-Energie A Madagascar.

Wood remains the principal energy source  the in Madagascar. Its use is an origin of  and atmospheric pollution.  The objective of this paper is to estimate the acifification and climate warming potentials of of firewood by Life Cycle Assessment from its cultivation to its use. A comparison between charcoal and firewood is carried out. One mégajoule of energy issue from firewood corresponds to 0,19kg eq CO2  greenhouse gases emission and 177.98 10-6 kg eq SO2 of air emissions. Charcoal emits four times more air emissions and nine times more greenhouse gases than firewood because of carbonization  during its production