Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

Background Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio

Optimisation of an oak chips-grape mix maceration process. Influence of chip dose and maceration time

[EN] Oak chips-related phenolics are able to modify the composition of red wine and modulate the colour stability. In this study, the effect of two maceration techniques, traditional and oak chips-grape mix process, on the phenolic composition and colour of Syrah red wines from warm climate was studied. Two doses of oak chips (3 and 6 g/L) at two maceration times (5 and 10 days) during fermentation was considered. Changes on phenolic composition (HPLC–DAD–MS), copigmentation/polymerisation (spectrophotometry), and colour (Tristimulus and Differential Colorimetry) were assessed by multivariate statistical techniques. The addition of oak chips at shorter maceration times enhanced phenolic extraction, colour and its stabilisation in comparison to the traditional maceration. On contrast, increasing chip dose in extended maceration time resulted in wines with lighter and less stable colour. Results open the possibility of optimise alternative technological applications to traditional grape maceration for avoiding the common loss of colour of wines from warm climate

Use of environmental isotopes to assess the sustainability of intensively exploited aquifer systems (2012‐2015)

Intensive exploitation of groundwater over longer period has led, in many important aquifers, to marked lowering of water tables, increasing exploitation costs, and often, to a progressive deterioration of water quality. Concentrated pumping may also alter flow patterns permanently with the risk of migration of pollutants into aquifers from the surrounding aquifers or surface water bodies due to lack of physical protection to prevent them. Isotope hydrology tools have proven to be very useful in assessing groundwater hydrology, addressing aspects related to recharge processes, delineation of flow patterns, water quality issues and interactions with other water bodies; this unique information can be further used to evaluate long term aquifer sustainability. The objective of the Coordinated Research Project F33019 is to develop and review approaches and methodologies, mostly based on the combined use of conventional hydrogeological techniques and environmental isotopes, to assess the response of groundwater systems to intensive exploitation and groundwater availability. Access to new dating tools and approaches for groundwater dating covering different time scales offers the possibility to evaluate changes in groundwater dynamics and flow patterns, providing key data to predict the evolution of aquifers and their sustainability as major sources of water. The CRP aims to assess the performance of these new tools and approaches and the possible adoption of these methods by water management experts

Catalytic conversion of 5-hydroxymethylfurfural (5-HMF) over Pd-Ru/FAU zeolite catalysts.

We present this study on FAU-type zeolites were prepared varying the Si/Al ratio (4, 5 and 6) and crystallization time (4, 6 and 8 h) to produce a highly pure and homogeneous material with enhanced surface area values. Bimetallic Pd-Ru and Pt-Ru (0.5 wt.% of each metal) were impregnated onto the zeolites matrix by the incipient wetness impregnation method. The materials were characterized by X-ray diffraction (XRD), nitrogen physisorption, Fourier Transform Infrared spectroscopy (FT-IR), Scattering Electronic Microscopy (SEM), Scattering and Transmission Microscopy (STEM), temperature-programmed desorption (TPD), temperature-programmed desorption (TPR) and Inductively Couples Plasma- Mass Spectrometer (ICP-MS). Results indicated that using lower Si/Al ratios favored the catalytic activity. Also, the longest crystallization time had a positive effect on surface area, homogeneous particle size distribution and crystallinity. The catalytic performance in the esterification of 5-hydroxymethylfurfural (5-HMF) to produce 5-acetoxymethylfurfural (AcMF) was investigated. The maximum 5-HMF conversion of 87.28 % was achieved using pure zeolite with relation Si/Al = 5, and 8 h of crystallization. Pd-Ru supported onto same zeolite showed a conversion of 84.22 %. The highest selectivity towards AcMF of 71.29 % with pure zeolite Si/Al = 5 and 8 h of crystallization was achieved, followed by Pd-Ru/FAU with Si/Al = 5 and 8 h of crystallization, achieving 60.42 %. Finally, results shown that the interaction between the properties of zeolitic support and the metallic species, specifically Pd, had a positive effect in the catalytic process the pristine zeolite showed improved catalytic characteristics related to its acid strength

Seroprevalence and Risk Factors Associated to Mycobacterium bovis in Wild Artiodactyl Species from Southern Spain, 2006–2010

The control of bovine tuberculosis (bTB) is at a critical point in the last stage of eradication in livestock. Wildlife species recently have emerged infected with TB in Europe, particularly ungulates in the Iberian Peninsula. Epidemiological information regarding TB in wild ungulates including affected species, prevalence, associated risk factors and appropriate diagnostic methods need to be obtained in these countries

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level

Tuberculosis in Alpacas (Lama pacos) Caused by Mycobacterium bovis▿

We report three cases of tuberculosis in alpacas from Spain caused by Mycobacterium bovis. The animals revealed two different lesional patterns. Mycobacterial culture and PCR assay yielded positive results for M. bovis. Molecular typing of the isolates identified spoligotype SB0295 and identical variable-number tandem repeat (VNTR) allele sizes