137 research outputs found
Site-dependent Local Spin Susceptibility and Low-energy Excitation in a Weyl Semimetal WTe
Site-dependent local spin susceptibility is investigated with Te
nuclear magnetic resonance in a Weyl semimetal WTe. The nuclear
spin-lattice relaxation rate shows a dependence of the square of
temperature at high temperatures, followed by a constant behavior below 50
K. The temperature dependence features Weyl fermions appearing around the
linearly crossing bands. The Knight shift scales to the square root of
, corroborating a predominant spin contribution in low-lying
excitation. The observed dependence of and on the four Te sites
shows the site-dependent electron correlation and density of states. The
angular profile of the NMR spectrum gives the anisotropic hyperfine coupling
tensor, consistent with hole occupations on Te sites.Comment: 6 pages, 5 figure
Small airway disease associated with Sjögren’s syndrome: Clinico-pathological correlations
SummaryBackgroundRelationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren’s syndrome have remained unclear.Subjects and methods: We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren’s syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren’s syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores.ResultsBronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren’s syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF50, MEF25 and air trapping.ConclusionsConstrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren’s syndrome
Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein
AbstractManipulation of protein stability with small molecules is a challenge in the field of drug discovery. Here we show that cellular retinoic acid binding protein-II (CRABP-II) can be specifically degraded by a novel compound, SNIPER-4, consisting of (−)-N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butyryl]-l-leucine methyl ester and all-trans retinoic acid that are ligands for cellular inhibitor of apoptosis protein 1 (cIAP1) and CRABP-II, respectively. Mechanistic analysis revealed that SNIPER-4 induces cIAP1-mediated ubiquitylation of CRABP-II, resulting in the proteasomal degradation. The protein knockdown strategy employing the structure of SNIPER-4 could be applicable to other target proteins
Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency
Iron plays the central role in oxygen transport by erythrocytes as a constituent of heme and hemoglobin. The importance of iron and heme is also to be found in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is deactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1−/− mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1−/− mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin
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