A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia

The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting ~2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA

Structural study of alpha-Bi2O3 under pressure

An experimental and theoretical study of the structural properties of monoclinic bismuth oxide (alpha-(BiO3)-O-2) under high pressures is here reported. Both synthetic and mineral bismite powder samples have been compressed up to 45 GPa and their equations of state have been determined with angle-dispersive x-ray diffraction measurements. Experimental results have been also compared with theoretical calculations which suggest the possibility of several phase transitions below 10 GPa. However, experiments reveal only a pressure-induced amorphization between 15 and 25 GPa, depending on sample quality and deviatoric stresses. The amorphous phase has been followed up to 45 GPa and its nature discussed.Financial support from the Spanish Consolider Ingenio 2010 Program (MALTA Project No. CSD2007-00045) is acknowledged. This work was also supported by Brazilian Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) under project 201050/2012-9, Spanish MICINN under projects MAT2010-21270-C04-01/03/04, Spanish MINECO under project CTQ2012-36253-C03-02, by Generalitat Valenciana through project GVA-ACOMP2013- 012 and from Vicerrectorado de Investigaci on dePereira, ALJ.; Errandonea, D.; Beltrán, A.; Gracia, L.; Gomis Hilario, O.; Sans, JA.; García-Domene, B.... (2013). Structural study of alpha-Bi2O3 under pressure. Journal of Physics: Condensed Matter. 25(47):475402-1-475402-12. https://doi.org/10.1088/0953-8984/25/47/475402S475402-1475402-12254

Communication, development, and social change in Spain: A field between institutionalization and implosion

This paper renders an account of the rapid institutionalization of the academic field of Communication for Development and Social Change (CDCS) in Spain in recent years following a period of neglect and marginalization. The ongoing expansion of the field of CDSC in the Spanish context is understood as a process of implosion, i.e. a collapse inwards, which results from the inconsistencies and weaknesses of fast and late institutionalization. The methodological approach for this inquiry is a documental review of both academic literature and research and institutional reports produced in Spain between 1980 and 2010. Based on this review, the paper contrasts the trajectory of the field in Spain with the debates at the international level, establishing relevant continuities and differences.This article is part of the Research Project (Ministry of Economy and Competitiveness, Spain) CSO2014-52005-R titled ‘Evaluation and Monitoring of Communication for Development and Social Change in Spain: design of indicators to measure its social impact’ (2015–2017)17 página

Genomic transformation and social organization during the Copper Age–Bronze Age transition in southern Iberia

The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting ~2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA.Introduction Results - Genetic substructure in the Iberian CA - Genetic turnover in the southern Iberian BA and the rise of El Argar - Mediterranean and central European ancestries shaped the genetic profile of southeastern BA groups in Iberia - A late Argar genetic outlier makes links to North Africa and the central Mediterranean - Insights into phenotypic variation, demography, and social correlates of CA and EBA El Argar societies Discussion Material and method

The Level of DING Proteins Is Increased in HIV-Infected Patients: In Vitro and In Vivo Studies

DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIV-infection by an overexpression of DING proteins

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Sixty-four new records for the flora of Peru from rapid biological inventories in the Peruvian Amazon

Durante el período 2000 – 2016, se llevaron a cabo 15 inventarios biológicos en áreas remotas en el pie de monte andino y el llano amazónico del Perú. En estos inventarios, 27 botánicos colectaron un total de 9397 especímenes de plantas vasculares fértiles. Hasta finales del 2017, más de la mitad de estos especímenes se han identificado a nivel de especie, de los cuales 64 especies y 2 géneros (Dicorynia y Monopteryx) representan nuevos registros para la flora del Perú. Si esta tasa de novedades se mantiene, el número de registros nuevos en el material de los inventarios podría aumentar, lo cual nos indica que aún queda mucho por descubrir en la flora andino-amazónica del Perú.Between 2000 and 2016 we carried out 15 rapid biological inventories in remote areas of the Andean foothills and Amazon basin in Peru. During these inventories, 27 botanists collected 9397 fertile vascular plant specimens. By the end of 2017, more than half of these specimens had been identified to species. Of the 2303 species identified to date, 64 species and 2 genera (Dicorynia and Monopteryx) are new records for the flora of Peru. If this rate of discovery proves typical, the number of new records for Peru in the rapid inventory material could increase, which indicates that there is still much to discover in the Peruvian flora

Bovine Tuberculosis in Doñana Biosphere Reserve: The Role of Wild Ungulates as Disease Reservoirs in the Last Iberian Lynx Strongholds

Doñana National Park (DNP) in southern Spain is a UNESCO Biosphere Reserve where commercial hunting and wildlife artificial feeding do not take place and traditional cattle husbandry still exists. Herein, we hypothesized that Mycobacterium bovis infection prevalence in wild ungulates will depend on host ecology and that variation in prevalence will reflect variation in the interaction between hosts and environmental risk factors. Cattle bTB reactor rates increased in DNP despite compulsory testing and culling of infected animals. In this study, 124 European wild boar, 95 red deer, and 97 fallow deer were sampled from April 2006 to April 2007 and analyzed for M. bovis infection. Modelling and GIS were used to identify risk factors and intra and inter-species relationships. Infection with M. bovis was confirmed in 65 (52.4%) wild boar, 26 (27.4%) red deer and 18 (18.5%) fallow deer. In the absence of cattle, wild boar M. bovis prevalence reached 92.3% in the northern third of DNP. Wild boar showed more than twice prevalence than that in deer (p<0.001). Modelling revealed that M. bovis prevalence decreased from North to South in wild boar (p<0.001) and red deer (p<0.01), whereas no spatial pattern was evidenced for fallow deer. Infection risk in wild boar was dependent on wild boar M. bovis prevalence in the buffer area containing interacting individuals (p<0.01). The prevalence recorded in this study is among the highest reported in wildlife. Remarkably, this high prevalence occurs in the absence of wildlife artificial feeding, suggesting that a feeding ban alone would have a limited effect on wildlife M. bovis prevalence. In DNP, M. bovis transmission may occur predominantly at the intra-species level due to ecological, behavioural and epidemiological factors. The results of this study allow inferring conclusions on epidemiological bTB risk factors in Mediterranean habitats that are not managed for hunting purposes. Our results support the need to consider wildlife species for the control of bTB in cattle and strongly suggest that bTB may affect animal welfare and conservation

GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively