Multiple, solid evidence support that Austropotamobius italicus is not native to Spain

Peer Reviewe

Desarrollo de Videojuego de Carreras Utilizando al Smartphone como Timón

Uno de los géneros más populares de videojuegos han sido los de carreras. Aquí hay una fuerte demanda por controladores con diseño de timón que hacen de la experiencia de juego más inmersiva y entretenida. No obstante, estos controladores suelen ser caros y no todos los jugadores pueden adquirirlos. En el afán de encontrar una alternativa más accesible que ofrezca la misma inmersión a los jugadores de este género se implementó SmartDrive, un videojuego de carreras para Android programado en Unity 3D. SmartDrive utiliza dos smartphones Android 5.0 o superior conectados vía un hotspot WiFi, uno se usa como pantalla del juego y otro como un timón gracias a sus sensores de movimiento. La validación contó con 30 participantes que jugaron y brindaron sus valoraciones mediante una encuesta. Los resultados finales destacaron la aceptación de SmartDrive en los participantes al ofrecer una experiencia inmersiva con una mecánica de juego novedosa e intuitiva, e implementada con recursos más económicos. Este estudio mostró el potencial de SmartDrive como una alternativa accesible y sin perder el grado de entretenimiento

Onset of microglial entry into developing quail retina coincides with increased expression of active caspase-3 and is mediated by extracellular ATP and UDP

Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7 th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina. However, the molecular mechanisms involved in this inflow are currently unclear. Extracellular nucleotides, such as ATP and UDP, have previously been shown to favor migration of microglia towards brain injuries because they are released by apoptotic cells and stimulate both chemotaxis and chemokinesis in microglial cells via signaling through purinergic receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in the entry and migration of microglial precursors into the developing retina. For this purpose, we used an experimental model system based on organotypic cultures of E6.5 quail embryo retina explants, which mimics the entry and migration of microglial precursors in the in situ developing retina. Inhibition of purinergic signaling by treating retina explants with either apyrase, a nucleotide-hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic receptors, significantly prevents the entry of microglial cells into the retina. In addition, treatment of retina explants with either exogenous ATP or UDP results in significantly increased numbers of microglial cells entering the retina. In light of these findings, we conclude that purinergic signaling by extracellular ATP and UDP is necessary for the entry and migration of microglial cells into the embryonic retina by inducing chemokinesis in these cells

PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability

[EN]Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that catalyze the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using WRL68 (HeLa derivate) cells, we previously showed that PARP-1 activation induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promoted cell death. In this work, LC-MS/MS-based phosphoproteomics in WRL68 cells showed that the oxidative damage induced by H2O2 increased the phosphorylation of YAP1, a transcriptional co-activator involved in cell survival, and modified the phosphorylation of other proteins involved in transcription. Genetic or pharmacological inhibition of PARP-1 in H2O2-treated cells reduced YAP1 phosphorylation and degradation and increased cell viability. YAP1 silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells exposed to oxidative damage. Supplementation of NAD+ also reduced YAP1 phosphorylation, suggesting that the loss of cellular NAD+ caused by PARP-1 activation after oxidative treatment is responsible for the phosphorylation of YAP1. Finally, PARP-1 silencing after oxidative treatment diminished the activation of the metabolic sensor AMPK. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates, we hypothesized that the loss of cellular NAD+ after PARP-1 activation may induce an energy stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in which PARP-1 activation reduced cell viability by promoting the phosphorylation and degradation of YAP1 through a mechanism that involves the depletion of NAD+

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

17 pags., 6 figs., 2 tabs.Sanchez-Martin et al. report a mode of action for naphthalene-diimides, a well-known class of G-quadruplexes ligands. Their work provides evidence of naphthalene-diimides targeting G-quadruplexes in ribosomal DNA, inducing a blockade of RNA polymerase I-mediated transcription and cell death. These compounds could be exploited in colorectal cancer treatment.This work was supported by the European Commission (TAR- BRAINFECT to J.A.G.-S.) and the National Institutes of Health (GM084946 to D.A.S.). The Government of Spain granted with PhD fellowships FPU16/ 05822 to V.S.-M. and FPU17/05413 to A.S.-L. The University of Almeria granted with PhD fellowship to M.O.-G. Funding for open access charge: Eu- ropean Commissio

CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism. In cerebrum of Coq9R239X mice, the deficit in SQR induces an increase in thiosulfate sulfurtransferase and sulfite oxidase, as well as modifications in the levels of thiols. As a result, biosynthetic pathways of glutamate, serotonin, and catecholamines were altered in the cerebrum, and the blood pressure was reduced. Therefore, this study reveals the reduction in SQR activity as one of the pathomechanisms associated with CoQ deficiency syndrome.This work was supported by grants from Ministerio de Economía y Competitividad, Spain, and the ERDF (SAF2013-47761-R, SAF2014-55523-R, RD12/0042/0011 and SAF201565786-R), from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (P10-CTS-6133), from the NIH (P01HD080642) and from the foundation “todos somos raros, todos somos únicos”. MLS is a predoctoral fellow from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía. LCL is supported by the “Ramón y Cajal” National Programme, Ministerio de Economía y Competitividad, Spain (RYC-2011-07643)

A Transcriptomic Approach to Search for Novel Phenotypic Regulators in McArdle Disease

McArdle disease is caused by lack of glycogen phosphorylase (GP) activity in skeletal muscle. Patients experience exercise intolerance, presenting as early fatigue and contractures. In this study, we investigated the effects produced by a lack of GP on several genes and proteins of skeletal muscle in McArdle patients. Muscle tissue of 35 patients and 7 healthy controls were used to identify abnormalities in the patients' transcriptomic profile using low-density arrays. Gene expression was analyzed for the influence of variables such as sex and clinical severity. Differences in protein expression were studied by immunoblotting and 2D electrophoresis analysis, and protein complexes were examined by two-dimensional, blue native gel electrophoresis (BN-PAGE). A number of genes including those encoding acetyl-coA carboxylase beta, m-cadherin, calpain III, creatine kinase, glycogen synthase (GS), and sarcoplasmic reticulum calcium ATPase 1 (SERCA1), were found to be downregulated in patients. Specifically, compared to controls, GS and SERCA1 proteins were reduced by 50% and 75% respectively; also, unphosphorylated GS and SERCA1 were highly downregulated. On BN-PAGE analysis, GP was present with GS in two muscle protein complexes. Our findings revealed some issues that could be important in understanding the physiological consequences of McArdle disease: (i) SERCA1 downregulation in patients could result in impaired calcium transport in type II (fast-twitch) muscle fibers, leading to early fatigability during exercise tasks involving type II fibers (which mostly use glycolytic metabolism), i.e. isometric exercise, lifting weights or intense dynamic exercise (stair climbing, bicycling, walking at a very brisk pace), (ii) GP and GS were found together in two protein complexes, which suggests a new regulatory mechanism in the activity of these glycogen enzymes

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naph thalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demon strate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting

Prisoners in Their Habitat? Generalist Dispersal by Habitat Specialists: A Case Study in Southern Water Vole (Arvicola sapidus)

Habitat specialists inhabiting scarce and scattered habitat patches pose interesting questions related to dispersal such as how specialized terrestrial mammals do to colonize distant patches crossing hostile matrices. We assess dispersal patterns of the southern water vole (Arvicola sapidus), a habitat specialist whose habitat patches are distributed through less than 2% of the study area (overall 600 km2) and whose populations form a dynamic metapopulational network. We predict that individuals will require a high ability to move through the inhospitable matrix in order to avoid genetic and demographic isolations. Genotypes (N = 142) for 10 microsatellites and sequences of the whole mitochondrial Control Region (N = 47) from seven localities revealed a weak but significant genetic structure partially explained by geographic distance. None of the landscape models had a significant effect on genetic structure over that of the Euclidean distance alone and no evidence for efficient barriers to dispersal was found. Contemporary gene flow was not severely limited for A. sapidus as shown by high migration rates estimates (>10%) between non-neighbouring areas. Sex-biased dispersal tests did not support differences in dispersal rates, as shown by similar average axial parent-offspring distances, in close agreement with capture-mark-recapture estimates. As predicted, our results do not support any preferences of the species for specific landscape attributes on their dispersal pathways. Here, we combine field and molecular data to illustrate how a habitat specialist mammal might disperse like a habitat generalist, acquiring specific long-distance dispersal strategies as an adaptation to patchy, naturally fragmented, heterogeneous and unstable habitats

Efficacy and Safety of Oral Administration of a Mixture of Probiotic Strains in Patients with Psoriasis: A Randomized Controlled Clinical Trial.

The aim of this 12-week randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of a probiotic mixture in the reduction of psoriasis severity. Ninety 18-70-year-old adults with plaque psoriasis were randomized into probiotic and placebo groups. At 12-week follow-up, 66.7% of patients in the probiotic group and 41.9% in the placebo group showed a reduction in Psoriasis Area and Severity Index of up to 75% (p < 0.05). A clinically relevant difference was observed in Physician Global Assessment index: 48.9% in the probiotic group achieved a score of 0 or 1, compared with 30.2% in the placebo group. The results of follow-up 6 months after the end of the study showed a lower risk of relapse after the intake of the probiotic mixture. Analysis of gut microbiota confirmed the efficacy of the probiotic in modulation of the microbiota composition