De la búsqueda de la función de la proteína Vmp1 a la caracterización de la autofagia en 'Dictyostelium discoideum'

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 10 de Junio de 201

Analiza, ocena i monitorowanie częstotliwości charakterystycznych pneumatycznego zespołu napędowego i wchodzącego w jego skład łożyska na podstawie widm częstotliwości oraz gęstości widmowej

This article shows the results of the study of the characteristic frequencies of pneumatic drive equipment and its suspension bearing. The analysis approaches one of the most important requirements of the industrial sector, which seeks to be recognised by the efficiency and performance of its equipment when compared to its coming economic competitors. For data collection and we have followed the ISO 10816 standards, thus using the values of speed in RMS, aiming to reduce the masking of these signals that occurs depending on whether they are high or low frequencies. The study will respond to one of the most important requirements found in the predictive and preventive control of industrial sites. The problem of the predictive systems of maintenance of equipment with bearings lies in the number of monitoring and analysis points that generate a high cost in time and human resources. The aim will be to determine which of all the study frequencies is the most significant and in which position and measurement axis has the biggest impact. To do this, we will analyse the rotation frequency of the blowing machine, the resulting frequency of all the frequencies, the frequency of the impulsion blades and finally the frequency of the bearing. The study would be able to predict when our equipment is going to suffer a failure, reducing the control points and the cost.Departamento de Ciencias Agroforestale

Dictyostelium transcriptional responses to Pseudomonas aeruginosa: common and specific effects from PAO1 and PA14 strains.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Pseudomonas aeruginosa is one of the most relevant human opportunistic bacterial pathogens. Two strains (PAO1 and PA14) have been mainly used as models for studying virulence of P. aeruginosa. The strain PA14 is more virulent than PAO1 in a wide range of hosts including insects, nematodes and plants. Whereas some of the differences might be attributable to concerted action of determinants encoded in pathogenicity islands present in the genome of PA14, a global analysis of the differential host responses to these P. aeruginosa strains has not been addressed. Little is known about the host response to infection with P. aeruginosa and whether or not the global host transcription is being affected as a defense mechanism or altered in the benefit of the pathogen. Since the social amoeba Dictyostelium discoideum is a suitable host to study virulence of P. aeruginosa and other pathogens, we used available genomic tools in this model system to study the transcriptional host response to P. aeruginosa infection. RESULTS: We have compared the virulence of the P. aeruginosa PAO1 and PA14 using D. discoideum and studied the transcriptional response of the amoeba upon infection. Our results showed that PA14 is more virulent in Dictyostelium than PA01using different plating assays. For studying the differential response of the host to infection by these model strains, D. discoideum cells were exposed to either P. aeruginosa PAO1 or P. aeruginosa PA14 (mixed with an excess of the non-pathogenic bacterium Klebsiella aerogenes as food supply) and after 4 hours, cellular RNA extracted. A three-way comparison was made using whole-genome D. discoideum microarrays between RNA samples from cells treated with the two different strains and control cells exposed only to K. aerogenes. The transcriptomic analyses have shown the existence of common and specific responses to infection. The expression of 364 genes changed in a similar way upon infection with one or another strain, whereas 169 genes were differentially regulated depending on whether the infecting strain was either P. aeruginosa PAO1 or PA14. Effects on metabolism, signalling, stress response and cell cycle can be inferred from the genes affected. CONCLUSION: Our results show that pathogenic Pseudomonas strains invoke both a common transcriptional response from Dictyostelium and a strain specific one, indicating that the infective process of bacterial pathogens can be strain-specific and is more complex than previously thought.Published versio

Geosciences for a Sustainable Planet: a new collaborative network to address societal and environmental challenges in the Anthropocene

The Geosciences for a Sustainable Planet network is an initiative reinforced by the recent integration of the Spanish Geological Survey (IGME) and the Oceanographic Spanish Institute (IEO) within the Spanish Scientific Research Council (CSIC). The network is aimed to provide Geosciences in Spain with a collaborative framework, to maximize synergies and address sustainability and future challenges with a planetary perspective. The network shares the strategic vision for the study and care of planet Earth as the only home available for our future, as embraced by many international organizations (e. g. the European Geosciences Union (EGU), United Nations Environment Programme (UNEP), International Union of Geological Sciences (IUGS), and the European Marine Board (EMB)). In Spain, Geosciences have played a fundamental role in properly assessing, managing, and seeking solutions for several natural and anthropogenic crises, e.g. the oil spill after the sinking of the Prestige petroleum vessel, the dumping of toxic mine sludge in Aznalcóllar, the eruption of the Cumbre Vieja volcano in La Palma island, the 2011 earthquake of Lorca, the environmental collapse of the Mar Menor oastal lagoon, or the decline in the groundwaters of Doñana National Park. Geoscientists have engaged as first responders with government agencies in emergency situations. Besides, geosciences is providing essential knowledge for public administration, as well as energy and mineral resources companies, water supply, contamination and waste elimination and reuse, and adaptation to geological and natural hazards. The network will enhance the capacity of the CSIC to respond to both, societal and public administration demands. Geosciences also provide the temporal and spatial scale to place current climate and environmental crises in the appropriate context. The network will implement outreach activities to illustrate the interactions of surface processes and biosphere with climatic fluctuations, atmospheric CO2 variations, sea-level changes, biodiversity collapses, etc, during the evolution of life on Earth over millions of years. We believe an essential aspect of science's contribution to sustainability is improving the communication of trans-disciplinary knowledge to citizens, future generations, administrations, and companies so they can take informed decisions. The Geoscience network will focus on outreach actions, training new generations of Geoscientists and technology and knowledge transfer. The Geosciences network seeks to facilitate the integration of research groups in the disciplines of Earth Sciences to improve our knowledge of the planet's geological processes across temporal scales ranging from millions of years to instrumental observation. This integration of basic and applied knowledge will enable Geosciences to provide tools to address the social challenges of the UN Sustainable Development Goals. Among them, we have selected four main areas: (1) energy and ecological transition, (2) access to water and geological resources, (3) mitigation and adaptation to geological hazards and risks, and (4) tools for solving environmental and climate crises. We believe that Geosciences network will offer the spatial dimension (from local to planetary) and temporal insight (natural variability beyond the human scale) to provide a common framework with a global, integrative, transversal, and multidisciplinary vision to tackle these challenges

Emergency department direct discharge compared to short-stay unit admission for selected patients with acute heart failure: analysis of short-term outcomes

Short stay unit (SSU) is an alternative to conventional hospitalization in patients with acute heart failure (AHF), but the prognosis is not known compared to direct discharge from the emergency department (ED). To determine whether direct discharge from the ED of patients diagnosed with AHF is associated with early adverse outcomes versus hospitalization in SSU. Endpoints, defined as 30-day all-cause mortality or post-discharge adverse events, were evaluated in patients diagnosed with AHF in 17 Spanish EDs with an SSU, and compared by ED discharge vs. SSU hospitalization. Endpoint risk was adjusted for baseline and AHF episode characteristics and in patients matched by propensity score (PS) for SSU hospitalization. Overall, 2358 patients were discharged home and 2003 were hospitalized in SSUs. Discharged patients were younger, more frequently men, with fewer comorbidities, had better baseline status, less infection, rapid atrial fibrillation and hypertensive emergency as the AHF trigger, and had a lower severity of AHF episode. While their 30-day mortality rate was lower than in patients hospitalized in SSU (4.4% vs. 8.1%, p < 0.001), 30-day post-discharge adverse events were similar (27.2% vs. 28.4%, p = 0.599). After adjustment, there were no differences in the 30-day risk of mortality of discharged patients (adjusted HR 0.846, 95% CI 0.637-1.107) or adverse events (1.035, 0.914-1.173). In 337 pairs of PS-matched patients, there were no differences in mortality or risk of adverse event between patients directly discharged or admitted to an SSU (0.753, 0.409-1.397; and 0.858, 0.645-1.142; respectively). Direct ED discharge of patients diagnosed with AHF provides similar outcomes compared to patients with similar characteristics and hospitalized in a SSU

Defects of mitochondrial RNA turnover lead to the accumulation of double-stranded RNA in vivo

The RNA helicase SUV3 and the polynucleotide phosphorylase PNPase are involved in the degradation of mitochondrial mRNAs but their roles in vivo are not fully understood. Additionally, upstream processes, such as transcript maturation, have been linked to some of these factors, suggesting either dual roles or tightly interconnected mechanisms of mitochondrial RNA metabolism. To get a better understanding of the turn-over of mitochondrial RNAs in vivo, we manipulated the mitochondrial mRNA degrading complex in Drosophila melanogaster models and studied the molecular consequences. Additionally, we investigated if and how these factors interact with the mitochondrial poly(A) polymerase, MTPAP, as well as with the mitochondrial mRNA stabilising factor, LRPPRC. Our results demonstrate a tight interdependency of mitochondrial mRNA stability, polyadenylation and the removal of antisense RNA. Furthermore, disruption of degradation, as well as polyadenylation, leads to the accumulation of double-stranded RNAs, and their escape out into the cytoplasm is associated with an altered immune-response in flies. Together our results suggest a highly organised and inter-dependable regulation of mitochondrial RNA metabolism with far reaching consequences on cellular physiology

Perioperative Chemoimmunotherapy Induces Strong Immune Responses and Long-Term Survival in Patients With Hla Class I-deficient Non-small Cell Lung Cancer

BACKGROUND: Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects. METHODS: Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data (programmed death-ligand 1 (PD-L1), TMB, TCR repertoire, TILs populations, bulk RNA-seq, and spatial transcriptomics (ST)) and clinical outcomes (pathological response and survival data) to study the activity of perioperative ChIO considering HLA class I defects. RESULTS: HLA-DEF tumors comprised 41.7% of analyzed tumors and showed a desert-like microenvironment at baseline, with lower PD-L1 levels and reduced immune infiltrate. However, perioperative ChIO induced similar complete pathological response (CPR) rates in both HLA-DEF and PRO tumors (50% and 60% respectively, p=0.670), as well as 3-year survival rates: Progression-free survival (PFS) and overall survival (OS) of 70% (95% CI 32.9% to 89.2%) for HLA-DEF, and PFS 71.4% (95% CI 40.6% to 88.2%) and OS 92.9% (95% CI 59.1% to 99.0%) for HLA-PRO (log-rank PFS p=0.909, OS p=0.137). Proof-of-concept ST analysis of a CPR HLA-DEF tumor after ChIO showed a strong immune response with tertiary lymphoid structures (TLS), CD4+T cells with HLA class II colocalization, and activated CD8+T cells. CONCLUSIONS: Our findings highlight the activity of perioperative ChIO, and the potential role of TLS and T-cell immune response, in NSCLC HLA-DEF tumors

Perioperative chemoimmunotherapy induces strong immune responses and long-term survival in patients with HLA class I-deficient non-small cell lung cancer

Background Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects.Methods Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data (programmed death-ligand 1 (PD-L1), TMB, TCR repertoire, TILs populations, bulk RNA-seq, and spatial transcriptomics (ST)) and clinical outcomes (pathological response and survival data) to study the activity of perioperative ChIO considering HLA class I defects.Results HLA-DEF tumors comprised 41.7% of analyzed tumors and showed a desert-like microenvironment at baseline, with lower PD-L1 levels and reduced immune infiltrate. However, perioperative ChIO induced similar complete pathological response (CPR) rates in both HLA-DEF and PRO tumors (50% and 60% respectively, p=0.670), as well as 3-year survival rates: Progression-free survival (PFS) and overall survival (OS) of 70% (95% CI 32.9% to 89.2%) for HLA-DEF, and PFS 71.4% (95% CI 40.6% to 88.2%) and OS 92.9% (95% CI 59.1% to 99.0%) for HLA-PRO (log-rank PFS p=0.909, OS p=0.137). Proof-of-concept ST analysis of a CPR HLA-DEF tumor after ChIO showed a strong immune response with tertiary lymphoid structures (TLS), CD4+T cells with HLA class II colocalization, and activated CD8+T cells.Conclusions Our findings highlight the activity of perioperative ChIO, and the potential role of TLS and T-cell immune response, in NSCLC HLA-DEF tumors

Accreditation of Spanish Engineering Programs, first experiences. The case of the Terrassa School of Engineering

The implementation of the European Space for Higher Education has entailed new requirements for Spanish Higher Education Programs. Regulations (RD 1393, 2007) stablish that university programs, in order to have official validity, must be submitted to an external evaluation process before their official implementation, denominated Validation, and to an ex-post process or Accreditation. Terrassa School of Engineering (EET) was one of the first schools in Spain to adapt to the European Space for Higher Education, in the academic period 2009-10 and then, one of the first university institutions submitted to an accreditation process. In this communication, the important role of the Internal Quality Assurance System in the assessment of the school’s programs is exposed as well as the approach followed in the key steps of the process: AccreditationPostprint (published version

ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing.

Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3\u27 phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3\u27 phosphates. Our results therefore propose a mechanism for non-canonical RNA processing in metazoan mitochondria, by identifying the role of ANGEL2