Recommendations on seismic actions on bridges

The paper describes the main features of a technical Recommendation first draft on Seismic Actions on Bridges, promoted by the Spanish Ministry of Public Works (MOPT). Although much more research is needed to clarify the seismic behaviour of the vast class of problems present in port structures the current state of the art allows at least a classificaton of subjects and the establishment of minimum requirements to guide the design. Also the use of more refined methods for specially dangerous situations needs some general guidelines that contribute to mantein the design under reasonable safety margins. The Recommendations of the Spanish MOPT are a first try in those directions

A methodology to introduce sustainability into the Final Year Project to foster sustainable engineering projects

The introduction of sustainability skills into higher education curricula is a natural effect of the increasing importance of sustainability in our daily lives. Topics like green computing, sustainable design or environmental engineering have become part of the knowledge required by today’s engineers. Furthermore, we strongly believe that the introduction of this skill will eventually enable future engineers to develop sustainable products, services and projects. The Final Year Project is the last academic stage facing students and a step towards their future professional engineering projects. As such, it constitutes a rehearsal for their professional future and an ideal opportunity for reflecting on whether their Final Year Project is sustainable or not, and to what extent. It also provides a good tool for reviewing the lessons learned about sustainability during the degree course and for applying them in a holistic and integrated way. In this paper, we present a guide that allows both students and advisors to think carefully about the sustainability of engineering projects, in particular the Final Year Project.Postprint (author’s final draft

In vivo and in vitro maturation of rabbit oocyte affects gene expression, mitochondrial distribution and apoptosis

In vivo-matured cumulus–oocyte complexes are valuable models in which to assess potential biomarkers of rabbit oocyte quality that contribute to enhanced IVM systems. In the present study we compared some gene markers of oocytes and cumulus cells (CCs) from immature, in vivo-matured and IVM oocytes. Moreover, apoptosis in CCs, nuclear maturation, mitochondrial reallocation and the developmental potential of oocytes after IVF were assessed. In relation to cumulus expansion, gene expression of gap junction protein, alpha 1, 43 kDa (Gja1) and prostaglandin-endoperoxide synthase 2 (Ptgs2) was significantly lower in CCs after in vivo maturation than IVM. In addition, there were differences in gene expression after in vivo maturation versus IVM in both oocytes and CCs for genes related to cell cycle regulation and apoptosis (V-Akt murine thymoma viral oncogene homologue 1 (Akt1), tumour protein 53 (Tp53), caspase 3, apoptosis-related cysteine protease (Casp3)), oxidative response (superoxide dismutase 2, mitochondrial (Sod2)) and metabolism (glucose-6-phosphate dehydrogenase (G6pd), glyceraldehyde-3-phosphate dehydrogenase (Gapdh)). In vivo-matured CCs had a lower apoptosis rate than IVM and immature CCs. Meiotic progression, mitochondrial migration to the periphery and developmental competence were higher for in vivo-matured than IVM oocytes. In conclusion, differences in oocyte developmental capacity after IVM or in vivo maturation are accompanied by significant changes in transcript abundance in oocytes and their surrounding CCs, meiotic rate, mitochondrial distribution and apoptotic index. Some of the genes investigated, such as Gja1, could be potential biomarkers for oocyte developmental competence in the rabbit model, helping improve in vitro culture systems in these species

PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus

[Aims/hypothesis]: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7.1 mouse model background and to characterise putative cellular mechanisms associated with preserved BCM. [Methods]: Two groups of RIP-B7.1 mice were genetically engineered to: (1) conditionally express either PAX4 (BPTL) or its diabetes-linked mutant variant R129W (mutBPTL) using doxycycline (DOX); and (2) constitutively express luciferase in beta cells through the use of RIP. Mice were treated or not with DOX, and EAD was induced by immunisation with a murine preproinsulin II cDNA expression plasmid. The development of hyperglycaemia was monitored for up to 4 weeks following immunisation and alterations in the BCM were assessed weekly by non-invasive in vivo bioluminescence intensity (BLI). In parallel, BCM, islet cell proliferation and apoptosis were evaluated by immunocytochemistry. Alterations in PAX4- and PAX4R129W-mediated islet gene expression were investigated by microarray profiling. PAX4 preservation of endoplasmic reticulum (ER) homeostasis was assessed using thapsigargin, electron microscopy and intracellular calcium measurements. [Results]: PAX4 overexpression blunted EAD, whereas the diabetes-linked mutant variant PAX4R129W did not convey protection. PAX4-expressing islets exhibited reduced insulitis and decreased beta cell apoptosis, correlating with diminished DNA damage and increased islet cell proliferation. Microarray profiling revealed that PAX4 but not PAX4R129W targeted expression of genes implicated in cell cycle and ER homeostasis. Consistent with the latter, islets overexpressing PAX4 were protected against thapsigargin-mediated ER-stress-related apoptosis. Luminal swelling associated with ER stress induced by thapsigargin was rescued in PAX4-overexpressing beta cells, correlating with preserved cytosolic calcium oscillations in response to glucose. In contrast, RNA interference mediated repression of PAX4-sensitised MIN6 cells to thapsigargin cell death. [Conclusions/interpretation]: The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus. The raw data for the RNA microarray described herein are accessible in the Gene Expression Omnibus database under accession number GSE62846

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved

A comprehensive review of primary strategies for tar removal in biomass gasification

In the current energy scenario, the production of heat, power and biofuels from biomass has become of major interest. Amongst diverse thermochemical routes, gasification has stood out as a key technology for the large-scale application of biomass. However, the development of biomass gasification is subjected to the efficient conversion of the biochar and the mitigation of troublesome by-products, such as tar. Syngas with high tar content can cause pipeline fouling, downstream corrosion, catalyst deactivation, as well as adverse impact on health and environment, which obstruct the commercialization of biomass gasification technologies. Since the reduction of tar formation is a key challenge in biomass gasification, a comprehensive overview is provided on the following aspects, which particularly include the definition and complementary classifications of tar, as well as possible tar formation and transformation mechanisms. Moreover, the adverse effects of tar on downstream applications, human health or environment, and tar analyzing techniques (online and off-line) are discussed. Finally, the primary tar removal strategies are summarized. In this respect, the effect of key operation parameters (temperature, ER and S/B), catalysts utilization (natural and supported metal catalysts) and the improvement of reactor design on tar formation and elimination was thoroughly analyzed.This work was carried out with the financial support from Spanish Ministries of Science, Innovation and Universities (RTI2018-098283-J-I00 (MCIU/AEI/FEDER, UE)) and Science and Innovation (PID2019-107357RB-I00 (MCIU/AEI/FEDER, UE) and TED2021-132056B-I00 (MCI/AEI/FEDER, UE)) and the Basque Government (IT1645-22). Moreover, this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 823745

Caracterización Proteómica in vivo de células endoteliales circulantes y células progenitoras de endoteliales an pacientes con síndrome coronario agudo

Comunicaciones a congreso

Estudio de la Estenosis Aórtica Valvular desde un punto de vista proteómico

Comunicaciones a congreso

Identification of protein expressed by aortic stenosis valves in the search for novel biomarkers

Comunicaciones a congreso

The effects of sildenafil citrate on the fetoplacental development and hemodynamics in a rabbit model of intrauterina growth restriction

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto–placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown–rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation