Latest results of dark matter detection with the DarkSide experiment

In this contribution the latest results of dark matter direct detection obtained by the DarkSide Collaboration are discussed. New limits on the scattering cross-section between dark matter particles and baryonic matter have been set. The results have been reached using the DarkSide-50 detector, a double-phase Time Projection Chamber (TPC) filled with 40Ar and installed at Laboratori Nazionali del Gran Sasso (LNGS). In 2018, the DarkSide Collaboration has performed three different types of analysis. The so-called high-mass analysis into the range between ∼ 10 GeV and ∼ 1000 GeV is discussed under the hypothesis of scattering between dark matter and Ar nuclei. The low-mass analysis, performed using the same hypothesis, extends the limit down to ∼1.8 GeV. Through a different hypothesis, that predicts dark matter scattering off the electrons inside of the Ar atom, it has been possible to set limits for sub-GeV dark matter masses

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Amino acid sequence, binding properties, and evolutionary relationships of the basic liver fatty acid-binding protein from the catfish Rhamdia sapo

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Isolation, amino acid sequence determination and binding properties of two fatty acid-binding proteins from axolotl (Ambistoma mexicanum) liver. Evolutionary relationships

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Crystallization and preliminary X-ray study of two liver basic fatty acid binding proteins

The fatty acid-binding proteins (FABPs) are a very well known protein family which includes the liver basic FABPs (Lb-FABPs), a subgroup so far characterized in several vertebrates but not in mammals. The most important difference recognized between the proteins in this subgroup and the better known mammalian liver FABPs (L-FABPs) is the stoichiometry of ligand binding: two fatty acid molecules in L-FABPs compared with one in Lb-FABPs. The only Lb-FABP with a known three-dimensional structure is that of chicken Lb-FABP, but the details of ligand binding are still unresolved as the crystals of the protein are grown at an acidic pH and the protein has been shown to lose its ligand under these conditions. The two proteins whose crystallizations are reported here are the second and third members of this subfamily to be crystallized. The crystals of axolotl Lb-FABP belong to either space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 65.38, c = 60.90 A, and diffract to a resolution of 2.0 A on a conventional source at room temperature. The crystals of toad Lb-FABP belong to either space group P4(1)22 or P4(3)22, with unit-cell parameters a = b = 48.14, c = 135.23 A, and diffract to 2.5 A resolution under the same conditions. It is expected that the solution of these two structures will help to clarify the structural differences between Lb-FABPs and L-FABPs and will possibly explain the different binding stoichiometries observed in these otherwise so similar protein subfamilies

Crystal structure of axolotl (Ambystoma mexicanum) liver bile acid-binding protein bound to cholic and oleic acid

The family of the liver bile acid-binding proteins (L-BABPs), formerly called liver basic fatty acid-binding proteins (Lb-FABPs) shares fold and sequence similarity with the paralogous liver fatty acid-binding proteins (L-FABPs) but has a different stoichiometry and specificity of ligand binding. This article describes the first X-ray structure of a member of the L-BABP family, axolotl (Ambystoma mexicanum) L-BABP, bound to two different ligands: cholic and oleic acid. The protein binds one molecule of oleic acid in a position that is significantly different from that of either of the two molecules that bind to rat liver FABP. The stoichiometry of binding of cholate is of two ligands per protein molecule, as observed in chicken L-BABP. The cholate molecule that binds buried most deeply into the internal cavity overlaps well with the analogous bound to chicken L-BABP, whereas the second molecule, which interacts with the first only through hydrophobic contacts, is more external and exposed to the solvent