Comportamiento diferido en estado fisurado de elementos de UHPFRC a flexotracción

[ES] En este trabajo se analiza el comportamiento a largo plazo de elementos de Hormigón de Ultra Alta Resistencia Reforzados con Fibras (en inglés UHPFRC) mediante una campaña experimental con tres tipos de probetas: cilíndricas (Ø100x200mm), prismáticas “R” (150x150x600mm) y prismáticas “S” (150x40x600mm). Se realizaron ensayos de retracción y de fluencia a flexión en estado fisurado, así como de caracterización tanto a resistencia a compresión como flexotracción. Las probetas cilíndricas se destinaron a retracción, fluencia en compresión y resistencia a compresión simple, en tanto que las prismáticas se destinaron a fluencia en flexión y resistencia a flexotracción. En las probetas R se realizó una entalla de 50 mm de profundidad y fueron prefisuradas hasta alcanzar un Crack Mouth Opening Displacement (CMOD) de 0,65mm. Las probetas S fueron prefisuradas sin entalla hasta alcanzar una pérdida de rigidez del 50%. Se montaron las probetas en los bastidores de fluencia en donde se mantuvo un nivel de carga del 50% de la resistencia residual obtenida del ensayo de prefisura para las probetas R y un nivel de carga entre el 68% y el 86% para las probetas S. Los ensayos de fluencia en flexión abarcaron 270 días, apreciándose una estabilizando más temprana para las probetas tipo S. De los resultados del ensayo de fluencia se calcularon los coeficientes y se compararon con los propuestos por distintos autores para el UHPFRC, dando como resultado que los valores de fluencia obtenidos de manera experimental son ligeramente menores que los propuestos quedando estos del lado de la seguridad.Los autores agradecen la financiación recibida desde el Ministerio de Economía y Competitividad a través de los Proyectos "BIA2012-35776 (FISNE)” y “BIA2016-78460- C3-1-R (BESHO/DEHMAR)”.Llano-Torre, A.; López, J.; Martí-Vargas, JR.; Serna, P. (2018). Comportamiento diferido en estado fisurado de elementos de UHPFRC a flexotracción. En HAC 2018. V Congreso Iberoamericano de hormigón autocompactable y hormigones especiales. Editorial Universitat Politècnica de València. 361-372. https://doi.org/10.4995/HAC2018.2018.6144OCS36137

An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

Glycogen-rich clear cell (GRCC) is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC). The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up

BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.Acknowledgements: We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias´ (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (grant numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, Project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, cofunded by ESF (`Investing in your future´) (grant number CP16/00033)

Historical and ecological drivers of the spatial pattern of Chondrichthyes species richness in the Mediterranean Sea

Chondrichthyes, which include Elasmobranchii (sharks and batoids) and Holocephali (chimaeras), are a relatively small group in the Mediterranean Sea (89 species) playing a key role in the ecosystems where they are found. At present, many species of this group are threatened as a result of anthropogenic effects, including fishing activity. Knowledge of the spatial distribution of these species is of great importance to understand their ecological role and for the efficient management of their populations, particularly if affected by fisheries. This study aims to analyze the spatial patterns of the distribution of Chondrichthyes species richness in the Mediterranean Sea. Information provided by the studied countries was used to model geographical and ecological variables affecting the Chondrichthyes species richness. The species were distributed in 16 Operational Geographical Units (OGUs), derived from the Geographical Sub-Areas (GSA) adopted by the General Fisheries Commission of the Mediterranean Sea (GFCM). Regression analyses with the species richness as a target variable were adjusted with a set of environmental and geographical variables, being the model that links richness of Chondrichthyes species with distance to the Strait of Gibraltar and number of taxonomic families of bony fishes the one that best explains it. This suggests that both historical and ecological factors affect the current distribution of Chondrichthyes within the Mediterranean Sea.Postprin

A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease

© 2020, The Author(s). Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases

Generic boundaries in subtribe Saussureinae (Compositae: Cardueae): Insights from Hyb-Seq data

The subtribe Saussureinae is a highly speciose group with more than 600 species distributed in the Northern Hemisphere and is particularly species-rich at the high mountains of central and eastern Asia. Saussurea and Jurinea are the two main genera described within the subtribe. However, up to 15 satellite genera are recognized in some recent taxonomic treatments with an analytical viewpoint. For the first time, we carried out a complete sampling to clarify generic boundaries based on a well-resolved phylogeny of Saussureinae. We employed a Hyb-Seq technique that targets 1061 nuclear conserved ortholog loci designed for Compositae. After a filtering of potential paralogs, 588 loci were retained to infer phylogenetic trees under concatenation and coalescence approaches. High branch support resolution was recovered at the generic level, but a non-monophyletic pattern was detected for most of the genera as they are currently circumscribed. Accordingly, we propose a new generic delimitation based on the three main clades recovered in the backbone tree, which are also in agreement with morphological evidence: Dolomiaea, Saussurea, and Jurinea. Following this classification into three genera, 18 new combinations are proposed. This new genus delineation will be used as a basis for future evolutionary studies in the Saussureinae.Financial support from the Ministerio de Ciencia e Innovación (Project CGL2015-66703-P MINECO/FEDER, UE and Ph.D. grant to Sonia Herrando-Moraira) and the Catalan government (“Ajuts a grups consolidats” 2017-SGR1116) is also greatly acknowledged. This study has been performed under the Ph.D. program “Plant Biology and Biotechnology” of the Autonomous University of Barcelona (UAB)INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION TAXONOMIC IMPLICATIONS NOTE ADDED IN PROOF AUTHOR CONTRIBUTIONS ACKNOWLEDGMENT

Expression Quantitative Trait Locus Analysis in Systemic Sclerosis Identifies New Candidate Genes Associated With Multiple Aspects of Disease Pathology

Objective: To identify the genetic variants that affect gene expression (expression quantitative trait loci [eQTLs]) in systemic sclerosis (SSc) and to investigate their role in the pathogenesis of the disease. Methods: We performed an eQTL analysis using whole-blood sequencing data from 333 SSc patients and 524 controls and integrated them with SSc genome-wide association study (GWAS) data. We integrated our findings from expression modeling, differential expression analysis, and transcription factor binding site enrichment with key clinical features of SSc. Results: We detected 49,123 validated cis-eQTLs from 4,539 SSc-associated single-nucleotide polymorphisms (SNPs) (PGWAS 0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in the blood cells, skin, or lung tissue of SSc patients. Transcription factor binding site analysis revealed enriched motifs of 24 transcription factors (5%) among SSc eQTLs, 5 of which were found to be differentially regulated in the blood cells (ELF1 and MGA), skin (KLF4 and ID4), and lungs (TBX4) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune-mediated diseases, of which only 3 have been tested in clinical trials in patients with SSc. Conclusion: The findings of the present study indicate a new layer to the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease

Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC

Island-like mountain radiations in Asia: The case study of the genera Saussurea and Jurinea

Trabajo presentado en el XIX International Botanical Congress (IBC 2017), celebrado en Shenzhen (China) del 23 al 29 de julio de 2017Evolutionary radiations represent events in which many species or lineages evolved from a common ancestor in a short period of time. Many plant radiations have been triggered by island-like ecological opportunities following mountain uplift; the mountain ranges with the steepest and widest environmental gradients, such as the Andes, are home of exceptional regional species pools (and also exceptional endemism rates), mainly derived from evolutionary radiations. The Himalayan-Qinghai-Tibetan Plateau (HQTP) and the adjacent Hengduan Mountains (HM) are considered one of the main biodiversity hotspots of the world thanks to its richness in species and endemics. Both regions show extreme altitudinal ranges compressed in short distances as a consequence of the collision of the Indian and Eurasian plates, and thus constitute ideal evolutionary scenarios to study diversification processes in mountain regions. We have identified two possible cases of alpine radiations in the Saussurea-Jurinea complex (Compositae-Cardueae), involving some 550 species in total. Saussurea shows an amazing number of species (more than 300) in the HQTP and Hengduan mountains, although a considerable number of species are also found on the west side of the mountains of Middle Asia (Tian Shan and Pamir-Alay). Jurinea, in contrast, has the highest number of species (150 sp.) in the Tian Shan and Pamir-Alay. Our general objectives are the following: a) To carry out an extensive sampling of Saussurea and Jurinea, especially centred in the two main radiation areas in the HQTP and Tian Shan mountains; b) To generate well-resolved phylogenies of both genera using a multi-loci approach through next-generation-sequencing (NGS) analyzed by Bayesian inference and parsimony, and explore coalescent-based species tree estimation with our NGS data set; c) On the basis of the new phylogenies, conduct phylogenetic comparative analyses and multi-model biogeographical inference to address the following questions: Do the alpine species of both genera in Asian mountains constitute clades with clearly higher rates of diversification than their lowland relatives? How many independent radiations took place in the complex? If several, did they occur at the same period, and are they comparable in terms of speciation rates? Which factors (intrinsic or extrinsic) shape species radiations, i.e., do the radiations follow a geographical model, an adaptive model, or a mixed model? Our results will be a major contribution to the study of alpine radiations especially in the HQTP, and will open a methodological pathway for the analysis of very large radiations in other genera.Peer reviewe

Integrating human and ecosystem health through ecosystem services frameworks

The pace and scale of environmental change is undermining the conditions for human health. Yet the environment and human health remain poorly integrated within research, policy and practice. The ecosystem services (ES) approach provides a way of promoting integration via the frameworks used to represent relationships between environment and society in simple visual forms. To assess this potential, we undertook a scoping review of ES frameworks and assessed how each represented seven key dimensions, including ecosystem and human health. Of the 84 ES frameworks identified, the majority did not include human health (62%) or include feedback mechanisms between ecosystems and human health (75%). While ecosystem drivers of human health are included in some ES frameworks, more comprehensive frameworks are required to drive forward research and policy on environmental change and human health