Spin-dependent scattering lengths of slow neutrons with nuclei by pseudomagnetic measurements

The spin-dependent scattering length of slow neutrons by the nuclei 23Na, 59Co, 63Cu, 65Cu, 195Pt, 197Au and 207Pb, as well as the mean value for the two isotopes of Tl and Ag in the natural element have been obtained by measuring the precession of the neutron spins as a function of nuclear polarization. A revised value for 91Zr is also given. The method has been extended for use with magnetic materials. Using f.c.c. and hexagonal cobalt, it is shown that these pseudomagnetic measurements may give precise information on the internal field seen by the nuclei.En mesurant la précession de spin de neutrons en fonction de la polarisation nucléaire, on a obtenu les valeurs de la longueur de diffusion dépendant du spin nucléaire pour les noyaux de 23Na, 59Co, 63Cu, 65Cu, 195Pt, 197Au et 207 Pb, ainsi qu'une valeur moyenne pour les deux isotopes du thallium et de l'argent dans l'élément naturel. On donne également une valeur corrigée pour 91Zr. La méthode a été étendue aux matériaux magnétiques. En utilisant du cobalt c.f.c. et hexagonal, on montre que les mesures pseudomagnétiques peuvent fournir des informations précises sur le champ interne vu par les noyaux

Identification of an allosteric binding site for RORγt inhibition

RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pocket. Binding at this non-canonical site induces an unprecedented conformational reorientation of helix 12 in the RORγt LBD, which blocks cofactor binding. The functional consequence of this allosteric ligand-mediated conformation is inhibition of function as evidenced by both biochemical and cellular studies. RORγt function is thus antagonized in a manner molecularly distinct from that of previously described orthosteric RORγt ligands. This brings forward an approach to target RORγt for the treatment of Th17-mediated autoimmune diseases. The elucidation of an unprecedented modality of pharmacological antagonism establishes a mechanism for modulation of nuclear receptors

Identification of an allosteric binding site for RORγt inhibition

RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pocket. Binding at this non-canonical site induces an unprecedented conformational reorientation of helix 12 in the RORγt LBD, which blocks cofactor binding. The functional consequence of this allosteric ligand-mediated conformation is inhibition of function as evidenced by both biochemical and cellular studies. RORγt function is thus antagonized in a manner molecularly distinct from that of previously described orthosteric RORγt ligands. This brings forward an approach to target RORγt for the treatment of Th17-mediated autoimmune diseases. The elucidation of an unprecedented modality of pharmacological antagonism establishes a mechanism for modulation of nuclear receptors