Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity

Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed on subsets of natural killer (NK) cells and T cells, for which no endogenous ligands are known. Here, we show that KLRG1 binds three of the classical cadherins (E-, N-, and R-), which are ubiquitously expressed in vertebrates and mediate cell–cell adhesion by homotypic or heterotypic interactions. By expression cloning using the mouse KLRG1 tetramer as a probe, we identified human E-cadherin as a xenogeneic ligand. We also identified a syngeneic interaction between mouse KLRG1 and mouse E-cadherin. Furthermore, we show that KLRG1 binds N- and R-cadherins. Finally, we demonstrate that E-cadherin binding of KLRG1 prevents the lysis of E-cadherin–expressing targets by KLRG1+ NK cells. These results suggest that KLRG1 ligation by E-, N-, or R-cadherins may regulate the cytotoxicity of killer cells to prevent damage to tissues expressing the cadherins

« Situation hégélienne en 1947 », précédé par une traduction de « Hegel en France (extrait) » de Georges Canguilhem

departmental bulletin pape

Growth of Acetaminophen Polymorphic Crystals and Solution-Mediated Phase Transition from Trihydrate to Form II in Agarose Gel

The growth of acetaminophen polymorphic crystals and the solution-mediated phase transition from trihydrate to form II in agarose gel were investigated. The form II crystals grown in gels, presumably because of the agarose content, dissolved less rapidly at high temperatures and were more stable than in water. The trihydrate crystals in the gel were also expected to be stabilized by containing agarose, but in fact the fine morphology resulted in reduced stability. The solution-mediated phase transition from trihydrate to form II via form II seeding took longer in the gel because the gel slowed down the dissolution of the trihydrate by hindering the dispersion of the form II seeds and delayed the growth of form II by reducing the diffusion rate of the molecules dissolved from the trihydrate. Delays in solution-mediated phase transition and changes in stability for crystals grown in gels indicate the effectiveness of gels in controlling polymorphisms in pharmaceutical compounds.Nishigaki A., Maruyama M., Tanaka S.I., et al. Growth of acetaminophen polymorphic crystals and solution-mediated phase transition from trihydrate to form II in agarose gel. Crystals 11, 1069 (2021); https://doi.org/10.3390/cryst11091069

Cooling of Compact Stars with Color Superconducting Phase in Quark Hadron Mixed Phase

We present a new scenario for the cooling of compact stars considering the central source of Cassiopeia A (Cas A). The Cas A observation shows that the central source is a compact star that has high effective temperature, and it is consistent with the cooling without exotic phases. The observation also gives the mass range of $M \geqslant 1.5 M_\odot$, which may conflict with the current plausible cooling scenario of compact stars. There are some cooled compact stars such as Vela or 3C58, which can be barely explained by the minimal cooling scenario, which includes the neutrino emission by nucleon superfluidity (PBF). Therefore, we invoke the exotic cooling processes, where a heavier star cools faster than lighter one. However, the scenario seems to be inconsistent with the observation of Cas A. Therefore, we present a new cooling scenario to explain the observation of Cas A by constructing models that include a quark color superconducting (CSC) phase with a large energy gap; this phase appears at ultrahigh density region and reduces neutrino emissivity. In our model, a compact star has CSC quark core with a low neutrino emissivity surrounded by high emissivity region made by normal quarks. We present cooling curves obtained from the evolutionary calculations of compact stars: while heavier stars cool slowly, and lighter ones indicate the opposite tendency without considering nucleon superfluidity. Furthermore, we show that our scenario is consistent with the recent observations of the effective temperature of Cas A during the last 10 years, including nucleon superfluidity.Comment: 5 pages, 4 figures, Accepted to Ap

The Inhibitory Effect of Kakkonto, Japanese Traditional (Kampo) Medicine, on Brain Penetration of Oseltamivir Carboxylate in Mice with Reduced Blood-Brain Barrier Function

Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression