On the applications of IBA techniques to biological samples analysis: PIXE and RBS

The analyticaltechniques based on ion beamsorIBA techniquesgive quantitativeinformationonelemental concentrationin samples of awide variety of nature. In this work, weinformation on elemental concentrationin samples of awide variety of nature. In this work, weinformation on elemental concentrationin samples of awide variety of nature. In this work, weinformation on elemental concentrationin samples of awide variety of nature. In this work, wefocus on PIXE technique,analyzingthick target biologicalspecimens (TTPIXE),using 3MeVfocus on PIXE technique,analyzingthick target biologicalspecimens (TTPIXE),using 3MeVfocus on PIXE technique,analyzingthick target biologicalspecimens (TTPIXE),using 3MeVfocus on PIXE technique,analyzingthick target biologicalspecimens (TTPIXE),using 3MeVprotons producedby an electrostaticaccelerator.Anuclear microprobewas used performingprotons producedby an electrostaticaccelerator.Anuclear microprobewas used performingprotons producedby an electrostaticaccelerator.Anuclear microprobewas used performingprotons producedby an electrostaticaccelerator.Anuclear microprobewas used performingPIXEandRBSsimultaneously,inordertosolvetheuncertaintiesproducedintheabsolutePIXEPIXEandRBSsimultaneously,inordertosolvetheuncertaintiesproducedintheabsolutePIXEPIXEandRBSsimultaneously,inordertosolvetheuncertaintiesproducedintheabsolutePIXEPIXEandRBSsimultaneously,inordertosolvetheuncertaintiesproducedintheabsolutePIXEquantifying. Theadvantages of using both techniquesand anuclear microprobearediscussed.quantifying.Theadvantages of using both techniquesand anuclear microprobearediscussed.quantifying.Theadvantages of using both techniquesand anuclear microprobearediscussed.quantifying.Theadvantages of using both techniquesand anuclear microprobearediscussed.Quantitative resultsare shown to illustrate themultielemental resolutionof the PIXE technique;Quantitativeresults are shown to illustrate themultielemental resolutionof the PIXE technique;Quantitativeresults are shown to illustrate themultielemental resolutionof the PIXE technique;Quantitativeresults are shown to illustrate themultielemental resolutionof the PIXE technique;forthis,abloodstandardwasused.forthis,abloodstandardwasused.forthis,abloodstandardwasused.forthis,abloodstandardwasused

Understanding the interplay of carbon and nitrogen supply for ectoines production and metabolic overflow in high density cultures of Chromohalobacter salexigens

Background The halophilic bacterium Chromohalobacter salexigens has been proposed as promising cell factory for the production of the compatible solutes ectoine and hydroxyectoine. This bacterium has evolved metabolic adaptations to efficiently grow under high salt concentrations by accumulating ectoines as compatible solutes. However, metabolic overflow, which is a major drawback for the efficient conversion of biological feedstocks, occurs as a result of metabolic unbalances during growth and ectoines production. Optimal production of ectoines is conditioned by the interplay of carbon and nitrogen metabolisms. In this work, we set out to determine how nitrogen supply affects the production of ectoines. Results Chromohalobacter salexigens was challenged to grow in media with unbalanced carbon/nitrogen ratio. In C. salexigens, overflow metabolism and ectoines production are a function of medium composition. At low ammonium conditions, the growth rate decreased importantly, up to 80%. Shifts in overflow metabolism were observed when changing the C/N ratio in the culture medium. 13C-NMR analysis of ectoines labelling revealed a high metabolic rigidity, with almost constant flux ratios in all conditions assayed. Unbalanced C/N ratio led to pyruvate accumulation, especially upon N-limitation. Analysis of an ect − mutant demonstrated the link between metabolic overflow and ectoine biosynthesis. Under non ectoine synthesizing conditions, glucose uptake and metabolic overflow decreased importantly. Finally, in fed-batch cultures, biomass yield was affected by the feeding scheme chosen. High growth (up to 42.4 g L−1) and volumetric ectoine yields (up to 4.21 g L−1) were obtained by minimizing metabolite overflow and nutrient accumulation in high density cultures in a low nitrogen fed-batch culture. Moreover, the yield coefficient calculated for the transformation of glucose into biomass was 30% higher in fed-batch than in the batch culture, demonstrating that the metabolic efficiency of C. salexigens can be improved by careful design of culture feeding schemes. Conclusions Metabolic shifts observed at low ammonium concentrations were explained by a shift in the energy required for nitrogen assimilation. Carbon-limited fed-batch cultures with reduced ammonium supply were the best conditions for cultivation of C. salexigens, supporting high density growth and maintaining high ectoines production.España, Ministerio de Ciencia e Innovación BIO2011-29233-C02-01España, Ministerio de Economía y Competitividad BIO2014-54411-C2-1-

Uncertainty Analysis in New Seismic Hazard Study of Spain Aimed at the Revision of the Spanish Building Code.

In this paper we present a global overview of the recent study carried out in Spain for the new hazard map, which final goal is the revision of the Building Code in our country (NCSE-02). The study was carried our for a working group joining experts from The Instituto Geografico Nacional (IGN) and the Technical University of Madrid (UPM) , being the different phases of the work supervised by an expert Committee integrated by national experts from public institutions involved in subject of seismic hazard. The PSHA method (Probabilistic Seismic Hazard Assessment) has been followed, quantifying the epistemic uncertainties through a logic tree and the aleatory ones linked to variability of parameters by means of probability density functions and Monte Carlo simulations. In a first phase, the inputs have been prepared, which essentially are: 1) a project catalogue update and homogenization at Mw 2) proposal of zoning models and source characterization 3) calibration of Ground Motion Prediction Equations (GMPE’s) with actual data and development of a local model with data collected in Spain for Mw < 5.5. In a second phase, a sensitivity analysis of the different input options on hazard results has been carried out in order to have criteria for defining the branches of the logic tree and their weights. Finally, the hazard estimation was done with the logic tree shown in figure 1, including nodes for quantifying uncertainties corresponding to: 1) method for estimation of hazard (zoning and zoneless); 2) zoning models, 3) GMPE combinations used and 4) regression method for estimation of source parameters. In addition, the aleatory uncertainties corresponding to the magnitude of the events, recurrence parameters and maximum magnitude for each zone have been also considered including probability density functions and Monte Carlo simulations The main conclusions of the study are presented here, together with the obtained results in terms of PGA and other spectral accelerations SA (T) for return periods of 475, 975 and 2475 years. The map of the coefficient of variation (COV) are also represented to give an idea of the zones where the dispersion among results are the highest and the zones where the results are robust

The photosynthetic cytochrome c 550 from the diatom Phaeodactylum tricornutum

The photosynthetic cytochrome c550 from the marine diatom Phaeodactylum tricornutum has been purified and characterized. Cytochrome c550 is mostly obtained from the soluble cell extract in relatively large amounts. In addition, the protein appeared to be truncated in the last hydrophobic residues of the C-terminus, both in the soluble cytochrome c550 and in the protein extracted from the membrane fraction, as deduced by mass spectrometry analysis and the comparison with the gene sequence. Interestingly, it has been described that the C-terminus of cytochrome c550 forms a hydrophobic finger involved in the interaction with photosystem II in cyanobacteria. Cytochrome c550 was almost absent in solubilized photosystem II complex samples, in contrast with the PsbO and Psb31 extrinsic subunits, thus suggesting a lower affinity of cytochrome c550 for the photosystem II complex. Under iron-limiting conditions the amount of cytochrome c550 decreases up to about 45% as compared to iron-replete cells, pointing to an iron-regulated synthesis. Oxidized cytochrome c550 has been characterized using continuous wave EPR and pulse techniques, including HYSCORE, and the obtained results have been interpreted in terms of the electrostatic charge distribution in the surroundings of the heme centre.This work was supported by the Spanish Ministry of Economy and Competitiveness (BIO2012-35271, BIO2015-64169-P, MAT2011-23861 and CTQ2015-64486-R) the Andalusian Government (PAIDI BIO-022) and the Aragón Government (Grupo consolidado B-18). All these grants were partially financed by the EU FEDER ProgramPeer reviewe

Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2)

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists have to deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers a number of specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.Also, special thanks to Ainhoa Torres and the Merck Health Foundation for funding and promoting the project and development of the Article.Peer Reviewe

Clinicopathological and Genomic Identification of Breast Cancers with No Impact on Mortality

Background. Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. Patients and Methods. To identify them, a retrospective observational study was carried out selecting patients without any palpable tumor and without axillary involvement, and a genomic analysis was performed with PAM50. Results. The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90–0.93) at 20 years and 0.96 (95% CI, 0.92–1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumors and in 9 (9.47%) luminal B tumors smaller than 1 cm, and in HER2 and basal type tumors, there were no metastatic events (20-year DMFI of 1.00). Conclusion. Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumor size less than 1 cm. Therefore, de-escalation of treatment should be considered

Elastic scattering and α -particle production in 6 He + 208 Pb collisions at 22 MeV

Experimental results of the elastic scattering of 6He on 208Pb at E LAB=22 MeV, measured at the CRC facility (Louvain-la-Neuve, Belgium), are presented, including results on the 4He production channel. These data were taken with full angular coverage and high angular resolution. Both experimental cross sections are compared with continuum discretized coupled channels and distorted-wave Born approximation calculations, where direct breakup and transfer to the continuum processes are considered. The elastic data confirm the absence of the Coulomb rainbow, while the distribution of α particles indicates that such production is mostly generated by transfer to the continuum.MICINN FPA2005-04460 FPA200502379 FPA2006-13807-c02-01 FPA2007-63074 FPA2009-07653 FPA2009-07387 FPA2010-22131-C02-01Junta de Andalucía FQM-4964Programa Consolider-Ingenio 2010 CSD2007-00042Comisión Europea HPRI-CT-1999-0011

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease

Activating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19

©2021 The Author(s). . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. This document is the Accepted, version of a Published Work that appeared in final form in The Journal of Infectious Diseases. To access the final edited and published work see https://doi.org/10.1093/infdis/jiab228Background: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. Here we investigate the role of Killer-cell Immunoglobulin-like receptor (KIR)/Human Leukocyte Antigen Class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. Methods: KIR and HLA-I genotyping and NK cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 non-infected controls. Results: NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe than mild/moderate patients and controls (83.7%, 55.7% and 36.2%, p<7.7x10-9). In mild/moderate patients HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared to patients with other HLA-B*15 subtypes and non-infected controls (90.9%, 42.9% and 47.3%, p<0.002, Pc=0.022). This strongly suggests that HLA-B*15:01 specifically presenting SARS-CoV-2 peptides could form a neo-ligand interacting with KIR3DS1. Similarly, a putative neo-ligand for KIR2DS4 could arise from other HLA-I molecules presenting SARS-CoV-2 peptides expressed on infected/activated lung antigen presenting cells. Conclusions: Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/Ligand interactions associated to disease severity

The genomic history of the Iberian Peninsula over the past 8000 years

We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula.We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming.We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry.We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean