ヘテロ金属の核数制御に伴うポリオキソバナデートの構造変化に関する研究

13301甲第4932号博士（理学）金沢大学博士論文要旨Abstract 以下に掲載：European Journal of Inorganic Chemistry 2017(3) pp.596-599 2017. Wiley-VCH. 共著者：Tatsuya Maruyama, Yuji Kikukawa, Keisuke Kawamoto, Yoshihito Hayash

ヘテロ金属の核数制御に伴うポリオキソバナデートの構造変化に関する研究

13301甲第4932号博士（理学）金沢大学博士論文本文Full 以下に掲載：European Journal of Inorganic Chemistry 2017(3) pp.596-599 2017. Wiley-VCH. 共著者：Tatsuya Maruyama, Yuji Kikukawa, Keisuke Kawamoto, Yoshihito Hayash

IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell–dependent type 2 innate immunity

C57BL/6 (B6) and B6 background STAT6−/− mice pretreated with IL-18 plus IL-2 showed prominent intestinal mastocytosis and rapidly expelled implanted adult worms of the gastrointestinal nematode Strongyloides venezuelensis. In contrast, identically pretreated mast cell–deficient W/Wv mice failed to do so. Thus, activated mucosal mast cells (MMC) are crucial for parasite expulsion. B6 mice infected with S. venezuelensis third-stage larvae (L3) completed parasite expulsion by day 12 after infection, whereas IL-18−/− or IL-18Rα−/− B6 mice exhibited marked impairment in parasite expulsion, suggesting a substantial contribution of IL-18–dependent MMC activation to parasite expulsion. Compared with IL-18−/− or IL-18Rα−/− mice, S. venezuelensis L3–infected STAT6−/− mice have poorly activated MMC and sustained infection; although their IL-18 production is normal. Neutralization of IL-18 and IL-2 further reduces expulsion in infected STAT6−/− mice. These results suggest that collaboration between IL-18–dependent and Th2 cell–dependent mastocytosis is important for prompt parasite expulsion

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients

Interplay of a non-conjugative integrative element and a conjugative plasmid in the spread of antibiotic resistance via suicidal plasmid transfer from an aquaculture Vibrio isolate

The capture of antimicrobial resistance genes (ARGs) by mobile genetic elements (MGEs) plays a critical role in resistance acquisition for human-associated bacteria. Although aquaculture environments are recognized as important reservoirs of ARGs, intra- and intercellular mobility of MGEs discovered in marine organisms is poorly characterized. Here, we show a new pattern of interspecies ARGs transfer involving a ‘non-conjugative’ integrative element. To identify active MGEs in a Vibrio ponticus isolate, we conducted whole-genome sequencing of a transconjugant obtained by mating between Escherichia coli and Vibrio ponticus. This revealed integration of a plasmid (designated pSEA1) into the chromosome, consisting of a self-transmissible plasmid backbone of the MOBH group, ARGs, and a 13.8-kb integrative element Tn6283. Molecular genetics analysis suggested a two-step gene transfer model. First, Tn6283 integrates into the recipient chromosome during suicidal plasmid transfer, followed by homologous recombination between the Tn6283 copy in the chromosome and that in the newly transferred pSEA1. Tn6283 is unusual among integrative elements in that it apparently does not encode transfer function and its excision barely generates unoccupied donor sites. Thus, its movement is analogous to the transposition of insertion sequences rather than to that of canonical integrative and conjugative elements. Overall, this study reveals the presence of a previously unrecognized type of MGE in a marine organism, highlighting diversity in the mode of interspecies gene transfer

Interplay of a non-conjugative integrative element and a conjugative plasmid in the spread of antibiotic resistance via suicidal plasmid transfer from an aquaculture Vibrio isolate

<div><p>The capture of antimicrobial resistance genes (ARGs) by mobile genetic elements (MGEs) plays a critical role in resistance acquisition for human-associated bacteria. Although aquaculture environments are recognized as important reservoirs of ARGs, intra- and intercellular mobility of MGEs discovered in marine organisms is poorly characterized. Here, we show a new pattern of interspecies ARGs transfer involving a ‘non-conjugative’ integrative element. To identify active MGEs in a <i>Vibrio ponticus</i> isolate, we conducted whole-genome sequencing of a transconjugant obtained by mating between <i>Escherichia coli</i> and <i>Vibrio ponticus</i>. This revealed integration of a plasmid (designated pSEA1) into the chromosome, consisting of a self-transmissible plasmid backbone of the MOB_H group, ARGs, and a 13.8-kb integrative element Tn<i>6283</i>. Molecular genetics analysis suggested a two-step gene transfer model. First, Tn<i>6283</i> integrates into the recipient chromosome during suicidal plasmid transfer, followed by homologous recombination between the Tn<i>6283</i> copy in the chromosome and that in the newly transferred pSEA1. Tn<i>6283</i> is unusual among integrative elements in that it apparently does not encode transfer function and its excision barely generates unoccupied donor sites. Thus, its movement is analogous to the transposition of insertion sequences rather than to that of canonical integrative and conjugative elements. Overall, this study reveals the presence of a previously unrecognized type of MGE in a marine organism, highlighting diversity in the mode of interspecies gene transfer.</p></div

A highly-flexible cyclic-decavanadate ligand for interconversion of dinuclear- and trinuclear-cobalt(II) and manganese(II) cores

金沢大学理工研究域物質化学系The structure transformation of multinuclear-metal-cores can change catalytic, optical, and magnetic properties. Cyclic decavanadate ligands exhibit versatility in the number and the direction of the coordination sites by changing the conformation to stabilize various multinuclear-metal-cores, while organic multinucleating ligands require specific design for each of the multimetal complexes due to their structure directing ability. The flexibility of cyclic decavanadate ligands is demonstrated here to achieve accommodation of dinuclear or trinuclear units by using the same ligand. The reaction of a dinuclear-cobalt-core-containing decavanadate [Co2(H2O)2V10O30]6- (Co2) with 1 equiv. of Co(OAc)2 (OAc = acetate) gave a trinuclear-cobalt-core-containing decavanadate [Co3(H2O)(OAc)V10O30]5- (Co3) in high yield. The central cobalt core exhibited an incomplete-cubane-type structure. The decavanadate ring contracts to accommodate a smaller dinuclear unit by taking a wavy conformation and expands to accommodate the larger trinuclear unit. The reverse reaction quantitatively proceeded by the addition of 5 equiv. of [VO3]- with respect to Co3. Although a trinuclear-manganese-core-containing decavanadate [Mn3(H2O)(OAc)V10O30]5- (Mn3) possesses the same structure as that of Co3, the addition of 5 equiv. of [VO3]- yielded a different structure of a dinuclear-manganese-core-containing decavanadate [Mn2V10O30]6- (Mn2) with two cyclic pentavanadate ligands sandwiching the manganese core. Thus, the conformations of the cyclic decavanadates are rearranged to respond to the central metal core structures. EXAFS study suggests both manganese complexes maintain the molecular structure in solution. The simultaneous analyses of the magnetic susceptibility data and the magnetization data revealed the switch of magnetic interaction modes from ferromagnetic in dinuclear complexes to mixed ferromagnetic and antiferromagnetic interactions in trinuclear complexes: the ferromagnetic interaction in dinuclear units of Co2 (J = 8.05 cm-1) and Mn2 (J = 0.76 cm-1) (Hex = -JS1S2), and the ferromagnetic and antiferromagnetic interactions in Co3 (J = -1.59 cm-1 and J′ = 13.6 cm-1) and Mn3 (J = -2.20 cm-1 and J′ = 0.07 cm-1) (Hex = -JSA1SA2 - J′[SA1SB + SA2SB]) were studied. © 2017 The Royal Society of Chemistry

Overexpression of Bcl2 in Osteoblasts Inhibits Osteoblast Differentiation and Induces Osteocyte Apoptosis

Bcl2 subfamily proteins, including Bcl2 and Bcl-XL, inhibit apoptosis. As osteoblast apoptosis is in part responsible for osteoporosis in sex steroid deficiency, glucocorticoid excess, and aging, bone loss might be inhibited by the upregulation of Bcl2; however, the effects of Bcl2 overexpression on osteoblast differentiation and bone development and maintenance have not been fully investigated. To investigate these issues, we established two lines of osteoblast-specific BCL2 transgenic mice. In BCL2 transgenic mice, bone volume was increased at 6 weeks of age but not at 10 weeks of age compared with wild-type mice. The numbers of osteoblasts and osteocytes increased, but osteoid thickness and the bone formation rate were reduced in BCL2 transgenic mice with high expression at 10 weeks of age. The number of BrdU-positive cells was increased but that of TUNEL-positive cells was unaltered at 2 and 6 weeks of age. Osteoblast differentiation was inhibited, as shown by reduced Col1a1 and osteocalcin expression. Osteoblast differentiation of calvarial cells from BCL2 transgenic mice also fell in vitro. Overexpression of BCL2 in primary osteoblasts had no effect on osteoclastogenesis in co-culture with bone marrow cells. Unexpectedly, overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteocytes, which had a reduced number of processes, gradually died with apoptotic structural alterations and the expression of apoptosis-related molecules, and dead osteocytes accumulated in cortical bone. These findings indicate that overexpression of BCL2 in osteoblasts inhibits osteoblast differentiation, reduces osteocyte processes, and causes osteocyte apoptosis

Patient Dose on the Radiological Diagnosis of Abdomen - The Situation of Patient nose at Hospitals in Okayama Prefecture -

In 1995, we have published a paper about the basic data on the relation between X-ray exposure equipment and patient dose in Vol. 17 of the Journal "Environment Research and Control". In this time, we questioned hospitals in Okayama Prefecture about exposure equipments of abdomen. And we compared each hospital's exposure equipments with the basic data, calculated each patient dose, then we studied that differences. Various imaging system, for example; screen/film or imaging plate has been used at each hospitals, so that exposure are various and patient doses are very different. The exposure equipment decide that the X-ray photograph is good or bad, so we cannot treat it easily. But we think that we have to try to take X-ray photographs which are suit the purpose of diagnosis which as a small patient dose as possible

Impact of Ambulation Status in Patients with End-stage Renal Disease on Hemodialysis due to Diabetic Nephropathy : The PREDICT Study

Article信州医学雑誌 68(3): 131-138(2020)journal articl