AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

Superconformal N=2, D=5 matter with and without actions

We investigate N=2, D=5 supersymmetry and matter-coupled supergravity theories in a superconformal context. In a first stage we do not require the existence of a Lagrangian. Under this assumption, we already find at the level of rigid supersymmetry, i.e. before coupling to conformal supergravity, more general matter couplings than have been considered in the literature. For instance, we construct new vector-tensor multiplet couplings, theories with an odd number of tensor multiplets, and hypermultiplets whose scalar manifold geometry is not hyperkaehler. Next, we construct rigid superconformal Lagrangians. This requires some extra ingredients that are not available for all dynamical systems. However, for the generalizations with tensor multiplets mentioned above, we find corresponding new actions and scalar potentials. Finally, we extend the supersymmetry to local superconformal symmetry, making use of the Weyl multiplet. Throughout the paper, we will indicate the various geometrical concepts that arise, and as an application we compute the non-vanishing components of the Ricci tensor of hypercomplex group manifolds. Our results can be used as a starting point to obtain more general matter-couplings to Poincare supergravity.Comment: 67 pages; v2: title of reference changed and small editing corrections; v3: small typing errors corrected, version published in JHEP; v4: typos corrected; v5: additional term in (2.109) and (4.11); v6: change of order of indices in (2.89

Long-term thermal sensitivity of Earth’s tropical forests

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate

Navigating New Landscapes: The Contribution of Socio-Legal Scholarship in Mapping the Plurality of International Economic Law and Locating Power in International Economic Relations

The evolution of international economic law in the past two decades has been characterised by the growth and diversification of international economic actors, the expansion in the substantive areas governed by international law, and, crucially, the proliferation of multiple sites of international economic governance. This web of multi-layered international economic governance is, in turn, underpinned by complex dynamics of power which structure the legal and economic relations between the subjects of international economic law and other actors impacted by international legal rules and regulation. The challenge for international legal scholarship lay not only in mapping the multiple sites of international economic governance but also in unmasking the power dynamics inherent in international economic relations. Locating and analysing power relations underlying international economic law is to crucial to understanding the cause and effect of international economic rules and institutions for rulemaking. Conventional legal scholarship with its doctrinal focus, while useful in providing the foundational basis for analysis, cannot adequately capture the complexity of contemporary international economic law. Socio-legal approaches may be able to overcome these epistemological limitations by supplying: a) the methodologies to study international economic law beyond a focus on rules and institutions; and b) the critical theoretical lens to understand the power dynamics inherent in international legal relations. The objective of this paper is twofold: firstly, it will seek to identify the contributions of socio-legal approaches to the study of international economic law; and secondly, it will explore how socio-legal scholarship can provide a methodological and theoretical framework to construct an understanding of the pluralistic nature of international economic regulatory regimes and their underlying dynamics of power. In doing so, the paper will also consider the value of juxtaposing an empirical methodology for mapping legal regimes with a critical normative approach for analysing power relations in international economic law

Sensitivity of South American tropical forests to an extreme climate anomaly

The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha −1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts