New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu antigen R

156 p. : graf.

Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by alpha subunit of the eukaryotic initiation factor 2 alpha phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. Cell Death and Disease (2010) 1, e54; doi:10.1038/cddis.2010.31; published online 15 July 2010

Eskaladako Fisiologia eta Balorazio Probak

Orain arte eskaladaren inguruan dagoen literaturan, antropometria, heltze indarra eta erantzun psikofisiologikoak aztertu dira nagusiki eta kontraesan ugari aurkitzen dira autore ezberdinen artean. Ikerketa honen bidez, kontraesan guzti hauek argitu nahi dira eta balorazio proba berri batzuen eraginkontarsuna aztertu. Gradu amaierako lan honen helburuak, lau balorazio proba ezberdin diseinatu, gauzatzea (heltze indarra, gauzatze aldagaiak, erantzun fisiologikoak eta RPE neurtuz) eta neurketa antropometrikoak egitea izan dira. Ondoren, maila ezberdineko eskalatzaileen eta bi sexuen arteko ezberdintasunak behatzeko. Ikerketan hiru emakume eta bederatzi gizonek parte hartu zuten, uniformeki maila ezberdineko taldetan banaturik. 1.taldea (6.gradukoak), emakume bat eta bi gizonek osatzen zuten, 2.taldea (7.gradukoak), emakume bat eta hiru gizonek eta 3.taldea (8.gradukoak), emakume bat eta lau gizonek. Diseinaturiko lau balorazio probak honako hauek izan ziren: 1.proba, suspentsio maximoa 1,8mmko regletan; 2.proba, trakzio kopuru maximoa; 3.proba, 7a zailtasuneko bia bat eskalatu akidura arte eta 4.proba, 6a+ zailtasuneko bia bat eskalatu akidura arte. Balorazio proba edo testekin hasi aurretik, atsedenean, bihotz maiztasuna eta tentsio arteriala neurtu eta esperientzia eta kirol praktikaren galdetegi bat pasa zitzaien. Ondoren, balorazio proba bakoitzaren aurretik eta ostean, gauzatze aldagaiak, heltze indarra, erantzun fisiologikoa eta RPE neurtu zitzaien. Erantzunei dagokionez, perfil antropometrikoan, gero eta maila altuagoko eskalatzaileek endomorfia baxuagoa dute eta emakumeek gizonezkoek baino balore altuagoak dituzte aldagai guztietan, gantz portzentaian izan ezik. Heltze indarrean aldiz, ez zen ezberdintasun adierazgarririk topatu hiru taldeen artean eta gizonezkoek emakumezkoek baino balore altuagoak izan arren, indar galera antzekoa dute. Erantzun fisiologikoetan ez zen ezberdintasun adierazgarririk topatu. Suspentsio maximoan (1.balorazio proban), gero eta maila altuagoko eskalatzaileek denbora gehiago irauten dute suspentsioan, trakzio kopuruetan aldiz (2.balorazio proba), ez dago ezberdintasun adierazgarririk. Kirol eskalada bertikalean aldiz (3. eta 4. balorazio probetan), maila altuagokoek distantzia luzeagoak eta mugimendu kopuru gehiago egiten dituzte proportzionalki denbora laburragoan. Ondorioz, helburuetako batzuk neurri handi batean bete dira. Laburbilduz, diseinaturiko balorazio probak erabilgarriak dira azkena izan ezik, eta antropometrian, heltze indarrean, suspentsio maximoan eta 3. balorazio probako gauzatze aldagaietan ezberdintasun adierazgarriak topatu dira.

The promoter of cell growth- and RNA protection-associated SND1 gene is activated by endoplasmic reticulum stress in human hepatoma cells

Background: Staphyloccocal nuclease domain-containing protein 1 (SND1) is involved in the regulation of gene expression and RNA protection. While numerous studies have established that SND1 protein expression is modulated by cellular stresses associated with tumor growth, hypoxia, inflammation, heat- shock and oxidative conditions, little is known about the factors responsible for SND1 expression. Here, we have approached this question by analyzing the transcriptional response of human SND1 gene to pharmacological endoplasmic reticulum (ER) stress in liver cancer cells. Results: We provide first evidence that SND1 promoter activity is increased in human liver cancer cells upon exposure to thapsigargin or tunicamycin or by ectopic expression of ATF6, a crucial transcription factor in the unfolded protein response triggered by ER stress. Deletion analysis of the 5'-flanking region of SND1 promoter identified maximal activation in fragment (-934, +221), which contains most of the predicted ER stress response elements in proximal promoter. Quantitative real- time PCR revealed a near 3 fold increase in SND1 mRNA expression by either of the stress- inducers; whereas SND1 protein was maximally upregulated (3.4-fold) in cells exposed to tunicamycin, a protein glycosylation inhibitor. Conclusion: Promoter activity of the cell growth- and RNA-protection associated SND1 gene is up-regulated by ER stress in human hepatoma cells.

An Embedded Stress Sensor for Concrete SHM Based on Amorphous Ferromagnetic Microwires

A new smart concrete aggregate design as a candidate for applications in structural health monitoring (SHM) of critical elements in civil infrastructure is proposed. The cement-based stress/strain sensor was developed by utilizing the stress/strain sensing properties of a magnetic microwire embedded in cement-based composite (MMCC). This is a contact-less type sensor that measures variations of magnetic properties resulting from stress variations. Sensors made of these materials can be designed to satisfy the specific demand for an economic way to monitor concrete infrastructure health. For this purpose, we embedded a thin magnetic microwire in the core of a cement-based cylinder, which was inserted into the concrete specimen under study as an extra aggregate. The experimental results show that the embedded MMCC sensor is capable of measuring internal compressive stress around the range of 1-30 MPa. Two stress sensing properties of the embedded sensor under uniaxial compression were studied: the peak amplitude and peak position of magnetic switching field. The sensitivity values for the amplitude and position within the measured range were 5 mV/MPa and 2.5 mu s/MPa, respectively.

MAB. Informe sobre el funcionamiento, organización y actividad del Mercado Alternativo Bursátil

El siguiente trabajo es un estudio sobre el Mercado Alternativo Bursátil para empresas en expansión,un modelo de mercado enfocado a PYMES que buscan expandirse.Supone una nueva fórmula de financiación alternativa para este tipo de empresas, que hasta ahora no podían acceder a los mercados bursátiles. A lo largo de este trabajo analizaremos su funcionamiento, características y evolución de la actividad que ha sufrido desde su creación en el 2009.