Mitochondrial control of cell death induced by hyperosmotic stress

HeLa and HCT116 cells respond differentially to sorbitol, an osmolyte able to induce hypertonic stress. In these models, sorbitol promoted the phenotypic manifestations of early apoptosis followed by complete loss of viability in a time-, dose-, and cell type-specific fashion, by eliciting distinct yet partially overlapping molecular pathways. In HCT116 but not in HeLa cells, sorbitol caused the mitochondrial release of the caspase-independent death effector AIF, whereas in both cell lines cytochrome c was retained in mitochondria. Despite cytochrome c retention, HeLa cells exhibited the progressive activation of caspase-3, presumably due to the prior activation of caspase-8. Accordingly, caspase inhibition prevented sorbitol-induced killing in HeLa, but only partially in HCT116 cells. Both the knock-out of Bax in HCT116 cells and the knock-down of Bax in A549 cells by RNA interference reduced the AIF release and/or the mitochondrial alterations. While the knock-down of Bcl-2/Bcl-XL sensitized to sorbitol-induced killing, overexpression of a Bcl-2 variant that specifically localizes to mitochondria (but not of the wild-type nor of a endoplasmic reticulum-targeted form) strongly inhibited sorbitol effects. Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control

Customization, extension and reuse of outdated hydrogeological software

Each scientist is specialized in his or her field of research and in the tools that he or she uses during the research in a specified site. Thus, he or she is the most suitable person for improving the tools by overcoming their limitations to realize faster and higher quality analysis. However, most scientists are not software developers. Hence, it is necessary to provide them with an easy approach that enables non-software developers to improve and customize their tools. This paper presents an approach for easily improving and customizing any hydrogeological software. It is the result of experiences with updating several interdisciplinary case studies. The main insights of this approachhave been demonstrated using four examples: MIX (FORTRAN-based), BrineMIX (C++-based), EasyQuim and EasyBal (both spreadsheet-based). The improved software has been proven to be a better tool for enhanced analysis by substantially reducing the computation time and the tedious processing of the input and output data files

Joining participatory approach and spatially-based modelling tools for groundwater resource management.

Although a lot of science has been produced on Water Resource Management (WRM) in the Information and Communication Technology (ICT) sector, WRM is still poorly addressed via scientific means. Some reasons for this may be: the underrated importance given to this topic at political and decision-making level; the low-capacity of the research environment to transfer results; and missing numerical modelling capacities at agencies and governing authorities. ICT may provide tools for water planning and management, as discussed within the ICT4WATER cluster initiative. Among these, GIS-integrated numerical modeling is a robust method to represent hydrological systems and to provide answers to problems of protection of groundwater resources. Because these tools require a high level of knowledge pertaining to various disciplines, they are often disregarded as complex “tricky games” providing unrealistic results. This is a barrier to the uptake of technologies for water management. To overcome this issue, the application of ICT tools has been combined with an innovative participatory approach, and large capacity building activities, in the framework of the H2020 FREEWAT project (FREE and open source software tools for WATer resource management; www.freewat.eu). The major result of the project consists in an open source and public domain, QGIS-integrated modeling platform for promoting WRM. FREEWAT capabilities have been demonstrated at 14 case studies in EU and non-EU Countries, where the effectiveness of few measures foreseen in River Basin Management Plans for achieving good status of water bodies was tested. At each case study, a Focus Group (FG) participated by local stakeholders (e.g., river basin authorities, research institutions, environmental protection agencies, environmental associations) was formed and seven meetings were organized. During these meetings, the objective of each case study, the methodology to be adopted, including definition of the conceptual model and of data needed, were discussed. The FG also took decisions on scenarios to be simulated for testing the feasibility of the foreseen measures. FGs aimed at demonstrating that WRM may be performed with open source and public domain software and participants’ perception on using ICT tools for WRM was discussed. Some of the implemented models are now being used for operational purposes: Vrbansky plato (Slovenia), where FREEWAT is used to monitor remediation of heating oil spillage and the water supply company intends to maintain and use developed groundwater flow model for managed groundwater recharge with induced riverbank filtration; the Bremerhaven case study (Germany), where the local water authority intends to use the developed groundwater flow model for predictions; the Scarlino-Follonica case study (Italy), where the model will be used by the regional authority to manage private groundwater remediation projects in a large industrial contaminated site; the Gozo case study (Malta), where the model is being developed to support the assessment of good groundwater quantitative status as part of the implementation of the Water Framework Directive

HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Ocular findings in Fabry disease in Colombian patients

La enfermedad de Fabry es un raro trastorno ligado al cromosoma X causado por deficiencia de la enzima alfa-galactosidasa y la consiguiente y progresiva acumulacion lisosomica de glucoesfingolipidos, especialmente la globotriaosilceramida, en multiples tejidos del organismo, incluido el ojo.En este reporte se presenta la primera serie de casos de manifestaciones oculares de la enfermedad de Fabry en Colombia, resaltando la importancia de los signos oculares como ayuda para el diagnostico temprano.Se presentan cinco casos de la enfermedad en Bogota y se da cuenta de las historias clinicas y los examenes oftalmologicos y de optometria, y se incluyen fotografias. En todos los pacientes se hallaron errores de refraccion y se evidencio el patron de cornea verticillata. Cuatro pacientes presentaban depositos de color cafe y castano claro en la capsula posterior del cristalino, y cuatro tenian tortuosidad vascular conjuntival y retiniana.El examen oftalmologico completo es importante para hacer un diagnostico oportuno con el fin de iniciar el tratamiento multidisciplinario y reducir la morbimortalidad.Fabry disease is a rare X-linked disorder caused by an alpha-galactosidase enzyme deficiency, which leads to a progressive lysosomal glycosphingolipids accumulation, mainly globotriaosylceramide, in multiple organism tissues including the eye. This case series describes the first ophthalmological Colombian report of Fabry disease highlighting the importance of ocular signs as markers of the disease, useful in diagnosis and treatment to avoid long-term complications that lead to a morbi-mortality increment. We describe five cases of Fabry disease from Bogota, Colombia, including a complete clinical history, ophthalmologic, optometric examination, and photographs. We found that all patients had refractive defects and that in all cases corneal verticillata pattern was found. Four patients presented with posterior capsule lens brown-beige deposits and four patients had conjunctival and retinal tortuous vessels. A complete ophthalmologic examination is important for prompt diagnosis, which is key to starting a multidisciplinary treatment and reducing morbi-mortality

Plan de negocio para la viabilidad comercial, operativa y econ?mica en la implementaci?n de un gimnasio para bebes de 4 meses a ni?os de 5 a?os, en Lima Norte

La obesidad en los ni?os representa un problema a largo plazo, afectando su salud al incrementarse el riesgo de padecer enfermedades cardiovasculares o diabetes; se recomienda desde la etapa infantil, una correcta alimentaci?n y una actividad f?sica frecuente, desarrollando h?bitos saludables. En ese sentido, la siguiente propuesta es un plan de negocio para implementar un gimnasio para bebes de 4 meses a 5 a?os en Lima Norte, considerando la importante tasa de crecimiento en este sector de la poblaci?n, determinando como mercado objetivo madres de los NSE B y C, de los distritos de Comas, San Mart?n de Porres, Los Olivos e Independencia. Del estudio de mercado se ha identificado una demanda potencial de servicios que contribuyan al desarrollo infantil y no se conocen gimnasios para ni?os menores de 5 a?os. La propuesta de valor del gimnasio Baby Gym es ofrecer el servicio de gimnasio para a trav?s de un ambiente l?dico se fortalezcan habilidades al propio ritmo de cada ni?o. Con una inversi?n inicial estimada de S/. 164,100.00 y un periodo de an?lisis de 10 a?os, se obtiene un VAN = S/. 96,977 y TIR de 29.3% respectivamente, con lo cual, el an?lisis financiero concluye que el negocio es viable