Hepatitis C virus relies on lipoproteins for its life cycle

Hepatitis C virus (HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production

Glutamate induces autophagy via the two-pore channels in neural cells

NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway. The involvement of TPC1/2 in glutamate-induced autophagy was also confirmed in SHSY5Y neuroblastoma cells. Finally, we show that glutamate leads to a NAADP-dependent activation of AMPK, which is required for autophagy induction, while mTOR activity is not affected by this treatment. Taken together, our results indicate that glutamate stimulates autophagy via NAADP/TPC/AMPK axis, providing new insights of how Ca2+ signalling glutamate-mediated can control the cell metabolism in the central nervous system

Imaging in white light with a thick-phase transmission holographic doublet

An afocal two-element holographic imaging system is presented. This system can be used to work in white light. The holographic optical elements (holographic lenses) are made as thick phase holograms on silver halide sensitized gelatin (SHSG) and they present a maximum diffraction efficiency of 75%. Geometrical conditions at reconstruction with coherent light and with white light are studied and a resolution test chart is imaged through the system, which shows a best resolution of 57 lines/mm for coherent illumination and 15 lines/mm for white light. The two-element holographic system presents a maximum diffraction efficiency of 56%

Entropy-based study of imaging quality in holographic optical elements

A method for obtaining the best image plane for holographic optical elements by the use of the concept of entropy is described. This method is applied to in-line holographic lenses with different values of spherical aberration. Numerical results show that for holograms with large aberrations the best image plane (obtained by the use of the concept of entropy) is different from the minimum-aberration-variance plane.This work was supported by the Direcció General d'Ensenyaments Universitaris i Investigació de la Generalitat Valenciana, Spain, project GV-1165/93

Iron overload down-regulates the expression of the HIV-1 Rev cofactor eIF5A in infected T lymphocytes

Background Changes in iron metabolism frequently accompany HIV-1 infection. However, while many clinical and in vitro studies report iron overload exacerbates the development of infection, many others have found no correlation. Therefore, the multi-faceted role of iron in HIV-1 infection remains enigmatic. Methods RT-qPCR targeting the LTR region, gag, Tat and Rev were performed to measure the levels of viral RNAs in response to iron overload. Spike-in SILAC proteomics comparing i) iron-treated, ii) HIV-1-infected and iii) HIV-1-infected/iron treated T lymphocytes was performed to define modifications in the host cell proteome. Data from quantitative proteomics were integrated with the HIV-1 Human Interaction Database for assessing any viral cofactors modulated by iron overload in infected T lymphocytes. Results Here, we demonstrate that the iron overload down-regulates HIV-1 gene expression by decreasing the levels of viral RNAs. In addition, we found that iron overload modulates the expression of many viral cofactors. Among them, the downregulation of the REV cofactor eIF5A may correlate with the iron-induced inhibition of HIV-1 gene expression. Therefore, we demonstrated that eiF5A downregulation by shRNA resulted in a significant decrease of Nef levels, thus hampering HIV-1 replication. Conclusions Our study indicates that HIV-1 cofactors influenced by iron metabolism represent potential targets for antiretroviral therapy and suggests eIF5A as a selective target for drug development

Molecular mechanisms of hepatitis C virus–induced hepatocellular carcinoma

n/

Disseny d'una cinta transportadora per el sector alimentari amb sistema fast-cleaning

En les fàbriques de la indústria alimentaria la neteja és un dels factors més importants juntament amb la prevenció de riscos, degut a que hi ha d’haver un equilibri entre tots dos per tal d’evitar la contaminació dels aliments i la possibilitat de lesions dels operaris. Aquests processos i maquinàries de les línies de treball estan sotmeses a dures revisions internes de les pròpies empreses i a auditories de la pròpia empresa i d’empreses externes per tal de validar que els productes que es generen en aquestes línies de treball compleixen la normativa. El Treball de Fi de Grau té com a objectiu principal el disseny d’una cinta transportadora amb un sistema de fast-cleaning per tal de poder retirar ràpid la banda del transportador i poder realitzar una neteja exhaustiva sense la possibilitat de que hi hagi racons de brutícia degut a que la banda no s’ha pogut extreure. El disseny es realitzarà mitjançant el software CAD SolidWorks i paral·lelament es realitzarà un estudi mecànic del transportador per a tal de verificar el disseny i es seguirà la normativa de materials aptes per a la indústria alimentaria.En las fábricas de la industria alimentaria la limpieza es uno de los factores más importantes junto con la prevención de riesgos, debido a que debe existir un equilibrio entre ambos para evitar la contaminación de los alimentos y la posibilidad de lesiones de los operarios. Estos procesos y maquinarias de las líneas de trabajo están sometidas a duras revisiones internas de las propias empresas y auditorías de la propia empresa y de empresas externas para validar que los productos que se generan en estas líneas de trabajo cumplen la normativa. El Trabajo de Fin de Grado tiene como objetivo principal el diseño de una cinta transportadora con un sistema de fast-cleaning para poder retirar rápido la banda del transportador y poder realizar una limpieza exhaustiva sin la posibilidad de que haya rincones de suciedad debido a que la banda no se ha podido extraer. El diseño se realizará mediante el software CAD SolidWorks y paralelamente se realizará un estudio mecánico del transportador para verificar el diseño y se seguirá la normativa de materiales aptos para la industria alimentaria.In the factories of the food industry, cleaning is one of the most important factors along with risk prevention, because there must be a balance between the two in order to avoid food contamination and the possibility of injuries to the food industry operators. These processes and machinery of the lines of work are subject to harsh internal reviews of the companies themselves and audits of the company itself and external companies in order to validate that the products generated in these lines of work comply with the regulations. The main objective of the Final Degree Project is to design a conveyor belt with a fast-cleaning system in order to be able to quickly remove the conveyor belt and to carry out a thorough cleaning without the possibility of dirt corners. because the band could not be extracted. The design will be carried out using SolidWorks CAD software and at the same time a mechanical study of the conveyor will be carried out in order to verify the design and the regulations for materials suitable for the food industry will be followed.Objectius de Desenvolupament Sostenible::12 - Producció i Consum Responsable

C/EBP-β Regulates Endoplasmic Reticulum Stress–Triggered Cell Death in Mouse and Human Models

Endoplasmic reticulum (ER) stress elicits the unfolded protein response (UPR), initially aimed at coping with the stress, but triggering cell death upon further stress. ER stress induces the C/EBP-® variant Liver-enriched Activating Protein (LAP), followed by the dominant-negative variant, Liver Inhibitory Protein (LIP). However, the distinct role of LAP and LIP in ER stress is unknown. We found that the kinetics of the ER stress-induced expression of LIP overlapped with that of the cell death in mouse B16 melanoma cells. Furthermore, inducible over-expression of LIP augmented ER stress-triggered cell death whereas over-expression of LAP attenuated cell death. Similar results were obtained in human 293T cells. Limited vasculature in tumors triggers hypoxia, nutrient shortage and accumulation of toxic metabolites, all of which eliciting continuous ER stress. We found that LAP promoted and LIP inhibited B16 melanoma tumor progression without affecting angiogenesis or accelerating the cell cycle. Rather, LAP attenuated, whereas LIP augmented tumor ER stress. We therefore suggest that C/EBP-® regulates the transition from the protective to the death–promoting phase of the UPR. We further suggest that the over-expression of LAP observed in many solid tumors promotes tumor progression by attenuating ER stress–triggered tumor cell death

Autophagy in development and regeneration: role in tissue remodelling and cell survival

Morphogenetic events that occur during development and regeneration are energy demanding processes requiring profound rearrangements in cell architecture, which need to be coordinated in timely fashion with other cellular activities, such as proliferation, migration and differentiation. In the last 15 years, it has become evident that autophagy, an evolutionarily-conserved catabolic process that mediates the lysosomal turnover of organelles and macromolecules, is an essential "tool" to ensure remodelling events that occur at cellular and tissue levels. Indeed, studies in several model organisms have shown that the inactivation of autophagy genes has a significant impact on embryogenesis and tissue regeneration, leading to extensive cell death and persistence of unnecessary cell components. Interestingly, the increased understanding of the mechanisms that confers selectivity to the autophagic process has also contributed to identifying development-specific targets of autophagy across species. Moreover, alternative ways to deliver materials to the lysosome, such as microautophagy, are also emerging as key actors in these contexts, providing a more complete view of how the cell component repertoire is renovated. In this review, we discuss the role of different types of autophagy in development and regeneration of invertebrates and vertebrates, focusing in particular on its contribution in cnidarians, platyhelminthes, nematodes, insects, zebrafish and mammals

Study of angular responses of mixed amplitude–phase holographic gratings: shifted Borrmann effect

We present theoretical results for angular responses of transmitted and diffracted beams in mixed amplitude–phase holographic gratings. Experimental results for gratings recorded in photographic emulsions and developed without a bleaching bath, with diffraction efficiencies of > 20%, are also presented. The model shows an angular shift between minimum transmittance and maximum diffraction efficiency when both index modulation and absorption coefficient modulation are present. Also, the Borrmann effect was found outside the Bragg angle. This method can be extended to a study of the mechanism of image formation in materials such as bacteriorhodopsin and azo-dye-doped polymers that exhibit both types of modulations (index and absorption)