Safety evaluation of the food enzyme endo-1,4-β-xylanase from genetically modified Aspergillus niger strain XYL

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A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies. In this study, we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway, the protein transport through the secretory pathway, and to the formation of a novel reversible non-membrane bound stress assembly, the Sec body that incorporates components of the ER exit sites. Sec body formation does not depend on membrane traffic in the early secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid droplet-like properties, and they act as a protective reservoir for ERES components to rebuild a functional secretory pathway after re-addition of amino-acids acting as a part of a survival mechanism. Taken together, we propose that the formation of these structures is a novel stress response mechanism to provide cell viability during and after nutrient stress

Fisiopatología de la incontinencia urinaria femenina

La incontinencia urinaria es definida por la International Continence Society como la queja ante cualquier salida involuntaria de orina. Se calcula que en el mundo alrededor del 30% de mujeres mayores de 60 años la padecen. En México no se han realizado estudios sistemáticos sobre la prevalencia de la incontinencia urinaria, pero se estima que entre el 15 y el 30% de mujeres mayores de 60 años la padecen. En el tratamiento de esta patología es importante conocer el sustrato anatómico y fisiológico de los procesos expulsivos femeninos contenidos en la región pélvica. En la presente revisión se describe los principales factores que desencadenan la incontinencia urinaria, los tratamientos para su control y la importancia de generar modelos animales que permitan conocer los factores asociados a su desarrollo

Método de obtención de datos útiles para evaluar la respuesta al tratamiento con 5-fluorouracilo (5-FU)

Método in vitro de obtención de datos útiles para evaluar la respuesta al tratamiento con 5-fluorouracilo (5-FU). La invención describe un Método in vitro de obtención de datos útiles para evaluar la respuesta al tratamiento con 5-fluorouracilo (5-FU) sólo o en combinación con otros principios activos como el IFN alpha de pacientes con cáncer de colon y mama.Peer reviewedServicio Andaluz de Salud, Universidad de Granada, Consejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools

Osteoporosis is one of the most common skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare outcomes. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent recommendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article mainly compiles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment

TORC2 mediates the heat stress response in Drosophila by promoting the formation of stress granules

The kinase TORis found in two complexes, TORC1,which is involved in growth control, and TORC2, whose roles are less well defined. Here, we asked whether TORC2 has a role in sustaining cellular stress. We show that TORC2 inhibition in Drosophila melanogaster leads to a reduced tolerance to heat stress, whereas sensitivity to other stresses is not affected. Accordingly, we show that upon heat stress, both in the animal and Drosophila cultured S2 cells, TORC2 is activated and is required for maintaining the level of its known target, Akt1 (also known as PKB). We show that the phosphorylation of the stress-activated protein kinases is not modulated by TORC2 nor is the heat-induced upregulation of heat-shock proteins. Instead, we show, both in vivo and in cultured cells, that TORC2 is required for the assembly of heat-induced cytoprotective ribonucleoprotein particles, the pro-survival stress granules. These granules are formed in response to protein translation inhibition imposed by heat stress that appears to be less efficient in the absence of TORC2 function.We propose that TORC2 mediates heat resistance in Drosophila by promoting the cell autonomous formation of stress granules

Método de obtención de datos útiles para evaluar, predecir y/o pronosticar la respuesta al tratamiento con análogos de pirimidina

[EN]The invention relates to an in vitro method for obtaining data that can be used to predict and prognosticate response to treatment with pyrimidine analogues and, preferably, with 5-fluorouracil (5-FU). The invention also relates to a kit and to the uses thereof.[ES] Método in vitro de obtención de datos útiles para predecir y pronosticar la respuesta al tratamiento conanálogos de pirimidina, y más preferiblemente con 5-fluorouracilo (S-FU), kit Yusos.Peer reviewedServicio Andaluz de Salud, Universidad de Granada, Consejo Superior de Investigaciones CientíficasA1 Solicitud de patente con informe sobre el estado de la técnic

Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation

Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein

Phospho-rasputin stabilization by Sec16 is required for stress granule formation upon amino acid starvation

Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein

EFSA Scientific Colloquium 24 – 'omics in risk assessment: state of the art and next steps

In recent years, the development of innovative tools in genomics, transcriptomics, proteomics and metabolomics (designated collectively as 'omics technologies) has opened up new possibilities for applications in scientific research and led to the availability of vast amounts of analytical data. The interpretation and integration of 'omics data can provide valuable information on the functional status of an organism and on the effect of external factors such as stressors. The European Food Safety Authority's (EFSA) 24th Scientific Colloquium on 'omics in risk assessment: state of the art and next steps explored the opportunities for integration of datasets produced via specific 'omics tools within the remit of EFSA's risk assessment approaches and tried to build further towards concrete paths of implementation. Discussions focused on genomics in microbial strain characterisation, metabolomics for the comparative assessment of GM plants and the use of 'omics for toxicological and environmental risk assessment. From the Colloquium it became clear that 'omics technologies are a valuable addition in some aspects of risk assessment of food and feed products and the environment, especially now that this technology is almost mature and stable. However, a consistent reporting framework for data collection, processing, interpretation, storage and curation should be further drawn up together with national and international organisations before 'omics technologies can be routinely used in risk assessment. For 'omics datasets in chemical and environmental risk assessments, the use of 'omics technologies alongside current toxicological or environmental risk assessment approaches is needed to re‐inforce confidence and expertise before implementation of these datasets as a standalone tool in risk assessment. Test cases could be worked out to enhance confidence in the use of 'omics datasets in risk assessment