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  • 1
    In: Endocrine Journal, Japan Endocrine Society, Vol. 66, No. 9 ( 2019), p. 777-786
    Type of Medium: Online Resource
    ISSN: 0918-8959 , 1348-4540
    Language: English
    Publisher: Japan Endocrine Society
    Publication Date: 2019
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-04-24)
    Abstract: Carbonaceous meteorites contain diverse soluble organic compounds. These compounds formed in the early solar system from volatiles accreted on tiny dust particles. However, the difference in the organic synthesis on respective dust particles in the early solar system remains unclear. We found micrometer-scale heterogeneous distributions of diverse CHN 1-2 and CHN 1-2 O compounds in two primitive meteorites: the Murchison and NWA 801, using a surface-assisted laser desorption/ionization system connected to a high mass resolution mass spectrometer. These compounds contained mutual relationships of ± H 2 , ± CH 2 , ± H 2 O, and ± CH 2 O and showed highly similar distributions, indicating that they are the products of series reactions. The heterogeneity was caused by the micro-scale difference in the abundance of these compounds and the extent of the series reactions, indicating that these compounds formed on respective dust particles before asteroid accretion. The results of the present study provide evidence of heterogeneous volatile compositions and the extent of organic reactions among the dust particles that formed carbonaceous asteroids. The compositions of diverse small organic compounds associated with respective dust particles in meteorites are useful to understand different histories of volatile evolution in the early solar system.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 3
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 2 ( 2022-04-18), p. 490-499
    Abstract: Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration–time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose–response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0–14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose–response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = −0.5; 95% CI: −1.1 to 0.1; per protocol set: P = 0.012, mean difference = −0.8; 95% CI: −1.3 to −0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose–response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Japanese Society of Pharmaceutical Health Care and Sciences ; 2021
    In:  Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Vol. 47, No. 4 ( 2021-4-10), p. 217-224
    In: Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences), Japanese Society of Pharmaceutical Health Care and Sciences, Vol. 47, No. 4 ( 2021-4-10), p. 217-224
    Type of Medium: Online Resource
    ISSN: 1346-342X , 1882-1499
    Language: English
    Publisher: Japanese Society of Pharmaceutical Health Care and Sciences
    Publication Date: 2021
    SSG: 15,3
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  • 5
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 2 ( 2019-01-22)
    Abstract: Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA ‐ PVAT ) and that surrounding the internal thoracic artery (ITA‐PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA ‐ PVAT , ITA ‐ PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA ‐ PVAT and that in CA ‐ PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis‐related molecules were observed in CA ‐ PVAT than those in SCAT and those in ITA ‐ PVAT . CA ‐ PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68‐positive and CD 11c‐positive M1 macrophages, a lower ratio of CD 206‐positive M2 to CD 11c‐positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome‐ and endoplasmic reticulum stress–related molecules, than did ITA ‐ PVAT and SCAT . Expression patterns of adipocyte developmental and pattern‐forming genes were totally different among SCAT , ITA ‐ PVAT, and CA ‐ PVAT . Conclusions The phenotype of ITA ‐ PVAT is closer to that of SCAT than that of CA ‐ PVAT , which may result from inherent differences in adipocytes. ITA ‐ PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 6
    In: Journal of Diabetes Investigation, Wiley, Vol. 11, No. 4 ( 2020-07), p. 878-887
    Abstract: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. Materials and Methods The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno‐Sobetsu Study. Results Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non‐smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. Conclusions The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 7
    In: Meteoritics & Planetary Science, Wiley, Vol. 58, No. 3 ( 2023-03), p. 405-420
    Abstract: Dmisteinbergite, a hexagonal form of CaAl 2 Si 2 O 8 , was found in a compact type A Ca‐Al‐rich inclusion (CAI) in the Allende CV3 chondrite. Scanning and transmission electron microscopic observations show that dmisteinbergite was always in contact with grossular and grossular was in contact with melilite. In addition, there is a crystallographic relationship between dmisteinbergite and anorthite. Based on the textural and crystallographic evidence, the following mineralogical alteration processes are proposed to have occurred in the CAI. (1) Melilite was replaced by grossular. High densities of vesicles in the grossular indicate that hydrogrossular might have been the primary alteration phase and dehydrated by later metamorphism. (2) Dmisteinbergite formed from (hydro)grossular through a reaction with Si‐rich fluid. (3) Nano‐sized minerals are formed within dmisteinbergite. (4) Dmisteinbergite was transformed to anorthite. (5) Both anorthite and dmisteinbergite were altered to nepheline. (6) Hydrogrossular was dehydrated to grossular. (Hydro)grossular, dmisteinbergite, anorthite, and nepheline in the CAI seem to have formed in the course of metasomatism that occurred in the Allende parent body. Except for the hydrogrossular dehydration, these reactions could have occurred at moderate temperature (200–250°C) in high pH fluids (pH 13–14) according to past experimental studies. Episodic changes in fluid composition seem to have occurred before reactions (2), (4), and (5), because these reactions were not completed before the next reaction started. Higher temperature is required for reactions (5) and (6) to occur. Our observation of the CAI suggests that it experienced multiple episodes of metasomatism as temperatures were rising in the Allende parent asteroid.
    Type of Medium: Online Resource
    ISSN: 1086-9379 , 1945-5100
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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    SSG: 16,12
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  • 8
    In: Journal of Diabetes Investigation, Wiley, Vol. 10, No. 4 ( 2019-07), p. 1059-1067
    Abstract: Xanthine oxidoreductase ( XOR ) is a rate‐limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance. Materials and Methods The association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid‐binding protein 4 ( FABP 4) and fibroblast growth factor 21 ( FGF 21), was investigated in 282 participants (male/female: 126/156) of the Tanno‐Sobetsu Study who were not taking medication. Results Women had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP 4 ( r  = 0.192, P   〈  0.001) and FGF 21 ( r  = 0.208, P   〈  0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level ( r  = −0.243, P  = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP 4 and FGF 21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP 4, but not that of adiponectin or FGF 21, remained as an independent predictor of plasma XOR activity. Conclusions Plasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 9
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: Organic compounds in asteroids and comets contain information about the early history of the Solar System. They could also have delivered organic material to early Earth. The Hayabusa2 spacecraft visited the carbonaceous asteroid Ryugu and collected samples of its surface materials, which were brought to Earth in December 2020. RATIONALE We investigated the macromolecular organic matter in the Ryugu samples, measuring its elemental, isotopic, and functional group compositions along with its small-scale structures and morphologies. Analytical methods used included spectro-microscopies, electron microscopy, and isotopic microscopy. We examined intact Ryugu grains and insoluble carbonaceous residues isolated by acid treatment of the Ryugu samples. RESULTS Organic matter is abundant in the Ryugu grains, distributed as submicrometer-sized organic grains and as organic matter dispersed in matrix. The Ryugu organic matter consists of aromatic carbons, aliphatic carbons, ketones, and carboxyls. The functional group compositions are consistent with those of insoluble organic matter (IOM) from primitive carbonaceous CI (Ivuna-type) and CM (Mighei-type) chondritic meteorites. Those meteorites experienced aqueous alteration (reactions with liquid water) on their parent bodies, which implies that the Ryugu organic material was also modified by aqueous alteration on the asteroid parent body. The functional group distributions of the Ryugu organic matter vary on submicrometer scales in ways that relate to the morphologies: nanoparticulate and/or nanoglobular regions are aromatic-rich, whereas organic matter associated with Mg-rich phyllosilicate matrix and carbonates is IOM-like or occurs as diffuse carbon. The observed macromolecular diversity provides further evidence that the organics were modified by aqueous alteration on Ryugu’s parent body. The diffuse carbon is similar to clay-bound organic matter that occurs in CI chondrites and the ungrouped C2-type meteorite Tagish Lake. No graphite-like material was found, which indicates that the Ryugu organic matter was not subjected to heating events on the parent body. The bulk hydrogen and nitrogen isotopic ratios of the Ryugu grains are between the bulk values of CI chondrites and the IOM in CI chondrites. Some carbonaceous grains showed extreme deuterium (D) and/or nitrogen-15 ( 15 N) enrichments or depletions. These indicate an origin in the interstellar medium or presolar nebula. The bulk hydrogen isotopic ratios of insoluble carbonaceous residues from the Ryugu samples are lower than those in CI and CM chondrites. The range of D enrichments are consistent with the ranges of CI, CM, and Tagish Lake chondrites. The nitrogen isotopic ratios of the IOM from Ryugu samples were close to those in CI chondrites. CONCLUSION The organic matter in Ryugu probably consists of primordial materials that formed during (or before) the early stages of the Solar System’s formation, which were later modified by heterogeneous aqueous alteration on Ryugu’s parent body asteroid. Although the surface of Ryugu is exposed to solar wind, impacts, and heating by sunlight, the macromolecular organics in the surface grains of Ryugu are similar in their chemical, isotopic, and morphological compositions to those seen in primitive carbonaceous chondrites. The properties of Ryugu’s organic matter could explain the low albedo of the asteroid’s surface. Chemical evolution of macromolecular organic matter in samples of asteroid Ryugu. Organic matter formed in the interstellar medium or in the outer region of the protoplanetary disk that formed the Solar System. It was then incorporated into a planetesimal—Ryugu’s parent body—where it experienced varying degrees of reactions with liquid water. An impact ejected material from the parent body, which reassembled to form Ryugu. Samples were brought to Earth by Hayabusa2. CREDIT: HIROSHIMA UNIVERSITY, JAXA, UNIVERSITY OF TOKYO, KOCHI UNIVERSITY, RIKKYO UNIVERSITY, NAGOYA UNIVERSITY, CHIBA INSTITUTE OF TECHNOLOGY, MEIJI UNIVERSITY, UNIVERSITY OF AIZU, AIST
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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    SSG: 11
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  • 10
    In: Endocrine Journal, Japan Endocrine Society, Vol. 65, No. 11 ( 2018), p. 1083-1092
    Type of Medium: Online Resource
    ISSN: 0918-8959 , 1348-4540
    Language: English
    Publisher: Japan Endocrine Society
    Publication Date: 2018
    detail.hit.zdb_id: 2133773-1
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