Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations

Discriminación de bosques de Araucaria araucana en el Parque Nacional Conguillío, centro-sur de Chile, mediante datos Landsat TM

Martin, JS (San Martin, Jose). Univ Talca, Inst Biol Vegetal & Biotecnol, Talca, ChileAraucaria forests (Araucaria araucana) have a tremendous ecological relevance; however, the information concerning their spatial distribution is still insufficient. They have only been classified according to small management scales, using satellite photos and images processed through conventional methods. The present study had as its objective to discriminate and characterize types of A. araucana forests in the Conguillio National Park, located in the Southern-Center Chile, through data derived from the Landsat-5 TM satellite and geographic information systems. The normalized difference vegetation index (NDVI) was satisfactorily related with variables corresponding to crown coverage and the diameter at breast height; thus, these index values were incorporated to the classification process. Using the digital elevation model and the NDVI, the effect provoked by the shadow was minimized. Seven types of forests, between dense and semi-dense-open, were discriminated in accordance with the accompanying species. The global reliability of the classification was 83.8 %. The greatest reliability for the producer was for the medium crown density forest of A. araucana - N. dombeyi (B1) (87.5 %); and for the consumer, for the high crown density forests of A. araucana - N. dombeyi (B1) and also for those of medium density (B2) (93 %). It is concluded that incorporating NDVI values and data derived from the digital elevation model to the satellite classification process, it is possible to discriminate araucaria forests with satisfactory reliability in areas of rough relief, which is very useful information for the management of these forestry ecosystems

Upconverting Carbon Nanodots from EDTA as Near-Infrared Activated Phototheranostic Agents

This work describes the synthesis of nitrogen-doped carbon nanodots (CNDs) synthesized from ethylene diamine tetra acetic acid (EDTA) as a precursor and their application as luminescent agents with a dual-mode theranostic role as near-infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized in tumor cells and exhibit no cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for photo-theranostic purposes, i.e.: simultaneous imaging and therapy can be carried out on cancer cells using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs NIR remote activation induces the in vitro killing of U251 MG cells. Through the use of flow imaging cytometry we have been able to successfully map and quantify the different type of cell deaths induced by the presence of intracellular superoxide anions (¿O2-) and hydrogen peroxide (H2O2) ROS species generated in situ upon NIR irradiation

Neoliberal economic policies’ effects on perceptions of social justice and sociopolitical participation in Portugal

Contemporary societies challenge long-standing projects of the “good society” and social equality through neoliberal economic policies. Social forms of uncertainty generated by financial deprivation, precarity, and inequality seem to have effects on agency and coping and so socioeconomic and psychological consequences. This study aims to test these relationships, as well as a hypothesis on the potential impact of these constructs on beliefs of sociopolitical control and social dominance, which have implications for social justice. A mediation model explores the effects of financial access (the manifest benefit of work) on psychosocial uncertainty (which reflects the perception of uncertainty in the social context and the experience of its consequences within work, relationships, and the adoption of self-defeating beliefs) and on emotional coping strategies towards uncertainty, and their effects on personal agency, sociopolitical control (SPC), and social dominance orientation (SDO). Data are derived from a study of 633 participants in Portugal. Although personal agency is influenced by financial access and psychosocial uncertainty, it is not proved as a significant mediator for SPC and SDO. Nevertheless, financial access, psychosocial uncertainty, and emotional coping significantly contribute to the model, supporting the hypothesis that financial access protects against psychosocial uncertainty. Both have an impact on SPC and SDO. Therefore, financial deprivation and psychosocial uncertainty potentially contribute to extremism and populism in societies characterised by socially created forms of uncertainty. Implications of results for psychological intervention, namely in vocational/professional counselling, are discussed

Factorial validity and measurement invariance of the Psychosocial Uncertainty Scale

This study presents the development of the Psychosocial Uncertainty Scale (PS-US), which articulates the perception of uncertainty in the social context and its psychological experience. It was validated with a sample of 1596 students and active professionals (employed and unemployed). By randomly dividing this sample in three sub-samples, the following analyses were performed: exploratory factor analysis (sample one: N = 827); preliminary confirmatory factor analysis identifying the final version of the scale (sample two: N = 382); confirmatory factor analysis (sample three: N = 387). Multi-group analysis was used to assess measurement invariance, gender, sociocultural level, and group of origin invariance, by using samples two and three. Group differences were explored with the complete sample through Multiple Indicators and Multiple Causes (MIMIC) Models. Associations between this scale and the Uncertainty response Scale were explored through Structural Equation Modelling. Exploratory and confirmatory analyses’ results showed good internal consistency and overall good psychometric qualities. The scale reached full metric invariance across groups, gender, SCL level and group of origin. Results highlight the sensitivity of the scale towards social vulnerability, proving the existence of sociocultural levels’ effects on experiences of psychosocial uncertainty within working contexts, relationships and community living and self-defeating beliefs; and gender and students versus professionals’ effects on psychosocial uncertainty. Furthermore, the scale associated significantly with Uncertainty Response Scale’s dimensions, specifically with emotional uncertainty, which can be considered a self-defeating strategy. Results suggest that emotional coping strategies, are explained by psychosocial uncertainty by 57%, and so, may have social origins

T cell receptor selection by and recognition of two class I major histocompatibility complex-restricted antigenic peptides that differ at a single position.

Peptides derived from HLA-Cw3 and HLA-A24 within region 170-179 differ by a single substitution, at position 173, and are both presented by the class I major histocompatibility complex molecule H-2Kd for recognition by murine cytolytic T lymphocytes (CTLs). As a first approach to understand the way T cell receptors (TCRs) intact with the HLA peptides, we have analyzed the TCR selection by, and recognition of, the two HLA antigenic sites. First, we have compared the TCR repertoires selected by HLA-Cw3 and HLA-A24, not only by sequencing the TCRs carried by CTL clones isolated and grown in vitro, but also by analyzing the TCRs expressed in vivo by peritoneal exudate lymphocytes from immune animals. Second, we have compared the TCR crossrecognition of HLA-A24 by CTLs selected by HLA-Cw3 with that of HLA-Cw3 by CTLs selected by HLA-A24. The combined analysis of TCR selection by and recognition of these two related HLA antigenic sites provides evidence that the TCR beta junctional regions interact with the amino-terminal part of the HLA peptides

Water Mass Transports and Pathways in the North Brazil- Equatorial Undercurrent Retroflection

The equatorial retroflection of the North Brazil Current (NBC) into the Equatorial Undercurrent (EUC) and its posterior tropical recirculation is a major regulator for the returning limb of the Atlantic Meridional Overturning Circulation. Indeed, most surface and thermocline NBC waters retroflect at the equator all the way into the central and eastern Atlantic Ocean, before they recirculate back through the tropics to the western boundary. Here, we use cruise data in the western equatorial Atlantic during April 2010 and reanalysis time series for the equatorial and tropical waters in both hemispheres in order to explore the recirculation pathways and transport variability. During the 1998–2016 period, the annual-mean EUC transports 15.1 ± 1.3 Sv at 32°W, with 2.8 ± 0.4 Sv from the North Atlantic and 11.4 ± 1.3 Sv from the South Atlantic. At 32°W most of the total EUC transport comes from the western boundary retroflection south of 3°N (7.2 ± 0.9 Sv), a substantial fraction retroflects north of 3°N (5.6 ± 0.4 Sv), and the remaining flow (2.3 Sv) joins through the interior basin. The South Atlantic subtropical waters feed the EUC at all thermocline depths while the North Atlantic and South Atlantic tropical waters do so at the surface and upper-thermocline levels. The EUC transport at 32°W has a pronounced seasonality, with spring and fall maxima and a range of 8.8 Sv. The 18 yr of reanalysis data shows a weak yet significant correlation with an Atlantic Niño index, and also suggests an enhanced contribution from the South Atlantic tropical waters during 2008–2016 as compared with 1997–2007En prensa3,17

A multiplex kindred with severe Buruli Ulcer dis playing Mendelian inheritance

Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacteriosis worldwide after tuberculosis and leprosy, and has been flagged in 1998 by the World Health Organization as an emerging neglected infectious disease.  The physiopathology of Mycobacterium ulcerans infection primarily involves the lipidic toxin mycolactone, a unique feature among mycobacteria. The resulting extensive skin ulcers and/or osteomyelitis cause pathologic scarring responsible for severe life-lasting functional disabilities in the affected population, mainly composed of children of less than 15 year of age.  Buruli ulcer mainly strikes in Western Sub-Saharan Africa but cases have been reported in more than 30 countries worldwide. A common characteristic of the endemic countries consists in the extreme clustering of BU cases in families living in the vicinity of slow-flowing or stagnant waters in rural areas.  However, only a fraction of these heavily exposed individuals develop Buruli ulcer, which leads us to hypothesize a genetic etiology accounting for this variability.    To tackle this issue, we adopted an extreme-phenotype strategy, which consisted in recruiting the most severe of  the  >1,500 BU cases diagnosed and treated during the last 7 years at the Centre de Détection et de Traitement de l\u27Ulcère de Buruli in Pobè, Benin. We report here the analysis of a single highly-informative consanguineous family in which two siblings were affected with exceptionally severe PCR-confirmed BU. The index case suffered from a multifocal edematous form of BU, which disseminated under treatment and involved the four limbs, eventually requiring amputation to heal. Her sister suffered from an edematous form which affected the right arm from shoulder to fingers.  Blood was obtained from the 2 parents, 2 affected and 3 unaffected children. DNA was processed for the genotyping of >900,000 Single Nucleotide Polymorphisms by the Affymetrix Genome-Wide 6.0 array.  After quality control procedures, 120,156 independent SNPs were used for linkage analysis by homozygosity mapping. Three regions, on chromosome 5 and 8, cosegregated with the affected status following a Mendelian recessive inheritance mode, i.e. were shared homozygous by descent by the 2 affected individuals but not the 3 unaffected siblings (yielding the maximum possible LOD score given the pedigree. Sequencing of genes in these regions is currently ongoing and show promising results.  This first description of a genetic etiology for extremely severe BU will have far reaching biological and medical implications. 

Primordialists and Constructionists: a typology of theories of religion

This article adopts categories from nationalism theory to classify theories of religion. Primordialist explanations are grounded in evolutionary psychology and emphasize the innate human demand for religion. Primordialists predict that religion does not decline in the modern era but will endure in perpetuity. Constructionist theories argue that religious demand is a human construct. Modernity initially energizes religion, but subsequently undermines it. Unpacking these ideal types is necessary in order to describe actual theorists of religion. Three distinctions within primordialism and constructionism are relevant. Namely those distinguishing: a) materialist from symbolist forms of constructionism; b) theories of origins from those pertaining to the reproduction of religion; and c) within reproduction, between theories of religious persistence and secularization. This typology helps to make sense of theories of religion by classifying them on the basis of their causal mechanisms, chronology and effects. In so doing, it opens up new sightlines for theory and research

Performance of prototypes for the ALICE electromagnetic calorimeter

The performance of prototypes for the ALICE electromagnetic sampling calorimeter has been studied in test beam measurements at FNAL and CERN. A $4\times4$ array of final design modules showed an energy resolution of about 11% /$\sqrt{E(\mathrm{GeV})}$ $\oplus$ 1.7 % with a uniformity of the response to electrons of 1% and a good linearity in the energy range from 10 to 100 GeV. The electromagnetic shower position resolution was found to be described by 1.5 mm $\oplus$ 5.3 mm /$\sqrt{E \mathrm{(GeV)}}$. For an electron identification efficiency of 90% a hadron rejection factor of $>600$ was obtained.Comment: 10 pages, 10 figure