Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes

Susumu Mitsutake, Kota Zama, Hazuki Yokota, Tetsuya Yoshida, Miki Tanaka, Masaru Mitsui, Masahito Ikawa, Masaru Okabe, Yoshikazu Tanaka, Tadashi Yamashita, Hiroshi Takemoto, Toshiro Okazaki, Ken Watanabe, Yasuyuki Igarashi, Dynamic Modification of Sphingomyelin in Lipid Microdomains Controls Development of Obesity, Fatty Liver, and Type 2 Diabetes, Journal of Biological Chemistry, Volume 286, Issue 32, 2011, Pages 28544-28555, ISSN 0021-9258, https://doi.org/10.1074/jbc.M111.255646

Antisynthetase syndrome: Pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases

AbstractObjectivesTo describe the pulmonary CT findings in patients with anti-ARS-antibody-positive interstitial lung disease (anti-ARS-ILD)MethodsThe CT findings of 64 patients with anti-ARS-ILD were retrospectively reviewed. The images were retrospectively reviewed independently by 2 chest radiologists, and the final decision on the CT findings was made by a third chest radiologist.ResultsThere were 16 male and 48 female patients, aged 54.2±13.4 years. Sixteen patients had anti Jo-1, 24 had anti-EJ, 9 had anti-PL-7, 7 had anti-PL-12, 5 had anti-KS, and 3 had anti-OJ antibodies. Overall, 63 patients (98.4%) had CT findings predominantly in the lower lobe; 61 patients (95.3%) showed peripheral opacities, and 47 patients (73.4%) showed peribronchovascular opacities. Ground-glass attenuation, consolidation, and reticulation showed similar distribution patterns. Regarding detailed CT findings, 89.1% of patients had lower volume loss, 76.6% had interlobular septal thickening, and 67.2% had thickening of bronchovascular bundles. The final radiologic diagnoses were as follows: inconsistent with usual interstitial pneumonia (UIP) in 63 patients (98.4%), which included nonspecific interstitial pneumonia (NSIP) in 35 patients (55.6%), organizing pneumonia (OP) in 4 patients (6.3%), and OP with fibrosis in 22 patients (34.9%).ConclusionsThe characteristic CT findings of patients with anti-ARS-ILD were areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which is compatible with NSIP. One-third of patients showed OP with fibrosis

Imatinib ameliorates bronchiolitis obliterans via inhibition of fibrocyte migration and differentiation

Background: Imatinib, a tyrosine kinase inhibitor, has been proposed as a potential anti-fibrotic agent for fibroproliferative diseases, including bronchiolitis obliterans (BO). However, the underlying anti-fibrotic mechanisms of the agent remain unclear. We evaluated whether bone (BM)-derived progenitor cells, fibrocytes, might be a target of imatinib in the attenuation of BO. Methods: We used a murine BO model induced by heterotopic tracheal transplantation and assessed the origin of fibroblasts by using green fluorescent protein-BM chimeric mice. We also evaluated the effects of imatinib on luminal obstruction and fibrocyte accumulation. The effects of imatinib on fibrocyte migration and differentiation were assessed by culturing fibrocytes in vitro. Results: In the murine BO model, tracheal allografts showed epithelial injury and developed complete luminal occlusion 28 days after transplantation. Most of the mesenchymal cells that had accumulated in the tracheal allograft were derived from BM cells. Imatinib treatment ameliorated the airway luminal occlusion and significantly reduced the number of fibrocytes in the allografts. In vitro studies showed that imatinib inhibited migration of cultured blood fibrocytes via the platelet-derived growth factor/platelet-derived growth factor receptor axis. Imatinib also inhibited differentiation of fibrocytes via suppression of c-Abl activity that was essential for the differentiation of monocytes to fibrocytes. Conclusions: Imatinib prevents airway luminal obstruction by inhibiting the migration and differentiation of fibrocytes. Fibrocytes may be a novel target in the prevention and treatment of BO. © 2016 International Society for Heart and Lung Transplantation.Embargo Period 12 month

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS

Vertical distribution patterns of pelagic cnidarians in the oceanic zone off Adélie Land, East Antarctica

第3回極域科学シンポジウム/第34回極域生物シンポジウム 11月26日（月） 国立極地研究所 ３階ラウン

Crystal structure of A-type ATP synthase catalytic nucleotide-binding subunit A from Pyrococcus horikoshii reveals a novel domain related in the

H+-transporting ATP synthase is a multi-subunit enzyme involved in the production of ATP, which is essential molecule for living organisms as a source of energy. Archaeal A-type ATPase (A-ATPase) is thought to act as a functional ATP synthase in Archaea and is thought to have chimeric properties of F-ATPase and V-ATPase. From the previous structural studies of F-ATPase, it is indicated that the major nucleotide-binding subunits α and β consist of three domains. The catalytic nucleotide-binding subunit A of V/A-ATPase contains an insertion of about 90 residues, which is absent from the F1-β subunit. Here we describe the first X-ray structure of the catalytic nucleotide-binding subunit A of the A1-ATPase determined at 2.55 Å resolution. A1-ATPase subunit A from Pyrococcus horikoshii consists of four domains. A novel domain, including a part of this insertion, corresponds to the “knob-like structure” observed in electron microscopy of A1-ATPase. Based on the structure, it is highly likely that this inserted domain is related to the peripheral stalk common to the A- and V-ATPases. The arrangement of this inserted domain suggests that this region plays an important role in A-ATPase as well as in V-ATPase