RESUMEN
Cortactin is a well-known regulatory protein of the host actin cytoskeleton and represents an attractive target of microbial pathogens like Helicobacter pylori. H. pylori manipulates cortactin's phosphorylation status by type-IV secretion-dependent injection of its virulence protein CagA. Multiple host tyrosine kinases, like FAK, Src, and Abl, are activated during infection, but the pathway(s) involved is (are) not yet fully established. Among them, Src and Abl target CagA and stimulate tyrosine phosphorylation of the latter at its EPIYA-motifs. To investigate the role of cortactin in more detail, we generated a CRISPR/Cas9 knockout of cortactin in AGS gastric epithelial cells. Surprisingly, we found that FAK, Src, and Abl kinase activities were dramatically downregulated associated with widely diminished CagA phosphorylation in cortactin knockout cells compared to the parental control. Together, we report here a yet unrecognized cortactin-dependent signaling pathway involving FAK, Src, and Abl activation, and controlling efficient phosphorylation of injected CagA during infection. Thus, the cortactin status could serve as a potential new biomarker of gastric cancer development.
Asunto(s)
Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Quinasa 1 de Adhesión Focal/genética , Infecciones por Helicobacter/genética , Helicobacter pylori/genética , Proteínas Oncogénicas v-abl/genética , Regulación Bacteriana de la Expresión Génica/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Interacciones Huésped-Patógeno/genética , Humanos , Fosforilación/genética , Familia-src Quinasas/genéticaRESUMEN
Arsenic contamination of groundwater is posing a serious challenge to drinking water supplies on a global scale. In India and Bangladesh, arsenic has caused the most serious public health issue in the world for nearly two decades. The aim of this work was to study an arsenic removal system based on reverse osmosis at pilot scale treating two different water sources from two different locations in the State of Bihar, India. For this purpose two villages, Bind Toli and Ramnagar in the Patna District were selected, both located very close to the river Ganga. The trials were conducted with aerated and non-aerated groundwater. It is the first time that the arsenic removal efficiency for aerated and non-aerated groundwater by reverse osmosis technology in combination with an energy-saving recovery system have been studied. As the principle of reverse osmosis requires a relatively high pressure, its energy demand is naturally high. By using an energy recovery system, this demand can be lowered, leading to an energy demand per liter permeate of 3-4Wh/L only. Due to high iron levels in the groundwater and as a consequence the precipitation of ferric (hydr)oxides, it was necessary to develop a granular media filter for the trials under aeration in order to protect the membrane from clogging. Two different materials, first locally available sand, and second commercially available anthracite were tested in the granular media filter. For the trials with aerated groundwater, total arsenic removal efficiency at both locations was around 99% and the arsenic concentration in permeate was in compliance with the WHO and National Indian Standard of 10µg/L. However, trials under anoxic conditions with non-aerated groundwater could not comply with this standard. Additionally a possible safe discharge of the reverse osmosis concentrate into an abandoned well was studied. It was observed that re-injection of reject water underground may offer a safe disposal option. However, long-term hydrogeological studies need to be conducted for confirmation.
Asunto(s)
Arsénico/aislamiento & purificación , Agua Potable/química , Agua Subterránea/química , Purificación del Agua/métodos , Carbón Mineral , Compuestos Férricos , Filtración , India , Ósmosis , Proyectos Piloto , Dióxido de Silicio , Abastecimiento de AguaRESUMEN
Malnutrition is a relevant risk factor for mortality for patients on maintenance hemodialysis treatment. In a retrospective study including 377 patients who began hemodialysis treatment between 1986 and 2001, we assessed the prevalence of different statuses of nutrition and the impact of the initial status of nutrition on the change in body weight and patient survival. We found an inverse relationship between body mass index (BMI, kg/m2) and the gain in body weight and BMI within 12 months of hemodialysis treatment. Underweight and normal weight patients had a substantial increase in these parameters, greatest in underweight subjects, whereas overweight and obese patients showed only a moderate increase or none (P =.0019, P =.00036). Adjusted mortality rates showed an inverse correlation with the initial BMI (P <.0001). There was a statistically significant difference in the mortality between patients with normal weight and overweight or obesity, respectively, showing a more favorable prognosis in overweight and obese patients (P =.0007; P =.022; log-rank, normal versus overweight, P =.012). Weight loss was the greatest independent risk factor for mortality in general. Adjusted hazard ratio of death was highest in underweight patients (3.999; CI, 2.708 to 5.905; P <.0001) and decreased to 2.251 (CI, 1.795 to 2.822; P <.0001) in normal weight, 1.927 (CI, 1.390 to 2.670; P <.0001) in overweight, and 1.651 (CI, 0.841 to 3.236; P =.1439) in obese subjects when patients with weight loss were compared with patients who preserved their initial weight or gained weight. Overall, the initial BMI has an influence on the change in body weight as well as on patient survival in general and in the case of weight loss in particular.