SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution.

International audienceHumans can be infected by SARS-CoV-2 either through inhalation of airborne viral particles or by touching contaminated surfaces. Structural and functional studies have shown that a single RBD of the SARS-CoV-2 homotrimer spike glycoprotein interacts with ACE2, which serves as its receptor 1,2. Binding of spike (S) protein to ACE2 and subsequent cleavage by the host protease transmembrane serine protease 2 (TMPRSS2) results in cell and virus membrane fusion and cell entry 1. Blocking of the ACE2 receptor by specific antibodies prevents viral entry 1,3-5. In vitro binding measurements have shown that SARS-CoV-2 S protein binds ACE2 with an affinity of around 10 nM, which is about tenfold tighter than the binding of the SARS-CoV S protein 2,4,6. It has been suggested that this is, at least partially, responsible for the higher infectivity of SARS-CoV-2 7. Recently, three major SARS-CoV2 variants of concern have emerged and mutations in the RBD of the spike proteins of these variants have further strengthened this hypothesis. Deep-mutational scanning of the RBD domain showed that the N501Y mutation in the Alpha variant to enhances binding to ACE2 7. The Beta variant has three altered residues in the ACE2-binding site (K417N, E484K and N501Y), and has spread extremely rapidly, becoming the dominant lineage in the Eastern Cape and Western Cape Provinces within weeks 8. The Gamma variant, with independent K417T, E484K and N501Y mutations, similar to the B.1.351 variant is spreading rapidly from the Amazon region 9. Another S mutation associated wit

A multilingual evaluation dataset for monolingual word sense alignment

Aligning senses across resources and languages is a challenging task with beneficial applications in the field of natural language processing and electronic lexicography. In this paper, we describe our efforts in manually aligning monolingual dictionaries. The alignment is carried out at sense-level for various resources in 15 languages. Moreover, senses are annotated with possible semantic relationships such as broadness, narrowness, relatedness, and equivalence. In comparison to previous datasets for this task, this dataset covers a wide range of languages and resources and focuses on the more challenging task of linking general-purpose language. We believe that our data will pave the way for further advances in alignment and evaluation of word senses by creating new solutions, particularly those notoriously requiring data such as neural networks. Our resources are publicly available at https://github.com/elexis-eu/MWSA.The authors would like to thank the three anonymous reviewers for their insightful suggestions and careful reading of the manuscript. This work has received funding from the EU’s Horizon 2020 Research and Innovation programme through the ELEXIS project under grant agreement No. 731015. The contributions in Bulgarian were partially funded by the Bulgarian National Interdisciplinary Research e-Infrastructure for Resources and Technologies in favor of the Bulgarian Language and Cultural Heritage, part of the EU infrastructures CLARIN and DARIAH – CLaDA-BG, Grant number DO1- 272/16.12.2019. This work is also supported by Sci- ence Foundation Ireland (SFI) under the Insight Center for Data Analytics (Grant Number SFI/12/RC/2289) and the Irish Research Council under the “Cardamom” Consolidator Laureate Grant (IRCLA/2017/129).peer-reviewed2020-05-1

The inflammation highway: metabolism accelerates inflammatory traffic in obesity

As humans evolved, perhaps the two strongest selection determinants of survival were a robust immune response able to clear bacterial, viral, and parasitic infection and an ability to efficiently store nutrients to survive times when food sources were scarce. These traits are not mutually exclusive. It is now apparent that critical proteins necessary for regulating energy metabolism such as peroxisome proliferator-activated receptors (PPARs), Toll-like receptors (TLRs), and fatty acid-binding proteins (FABPs) also act as links between nutrient metabolism and inflammatory pathway activation in immune cells. Obesity in humans is a symptom of energy imbalance: the scale has been tipped such that energy intake exceeds energy output and may be a result, in part, of evolutionary selection toward a phenotype characterized by efficient energy storage. As discussed in this review, obesity is a state of low-grade, chronic inflammation that promotes the development of insulin resistance and diabetes. Ironically, the formation of systemic and/or local, tissue-specific insulin resistance upon inflammatory cell activation may actually be a protective mechanism that co-evolved to repartition energy sources within the body during times of stress during infection. However, the point has been reached where a once beneficial adaptive trait has become detrimental to the health of the individual and an immense public health and economic burden. This article reviews the complex relationship between obesity, insulin resistance/diabetes, and inflammation, and while the liver, brain, pancreas, muscle, and other tissues are relevant, we focus specifically on how the obese adipose microenvironment can promote immune cell influx and sustain damaging inflammation that can lead to the onset of insulin resistance and diabetes. Finally, we address how substrate metabolism may regulate the immune response and discuss how fuel uptake and metabolism may be a targetable approach to limit or abrogate obesity-induced inflammation