In situ photoaffinity labeling of the target protein for lembehyne A, a neuronal differentiation inducer

AbstractA C36 linear acetylene alcohol, lembehyne A (LB-A), induces neuronal differentiation against neuroblastoma cells morphologically and also functionally. The differentiation and cytostatic effect induced by LB-A was specific to neuroblastoma, Neuro 2A cells. To identify the target protein for LB-A, a radioactive photoaffinity probe, [125I]18-(2′-azido-5′-iodo-benzoyloxy)-LB-18 ([125I]azido-LB-18), was synthesized. As a result of in situ labeling experiments against Neuro 2A cells, a protein of Mr 30 kDa was photolabeled specifically. This labeling was inhibited in the presence of LB-A or the active analogs of LB-A, whereas the inactive analogs showed no inhibitory effect on this labeling. These results suggest that this protein of Mr 30 kDa is the target protein for LB-A and may play an important role for the neuronal differentiation in neuroblastoma, Neuro 2A cells

Design report of the KISS-II facility for exploring the origin of uranium

One of the critical longstanding issues in nuclear physics is the origin of the heavy elements such as platinum and uranium. The r-process hypothesis is generally supported as the process through which heavy elements are formed via explosive rapid neutron capture. Many of the nuclei involved in heavy-element synthesis are unidentified, short-lived, neutron-rich nuclei, and experimental data on their masses, half-lives, excited states, decay modes, and reaction rates with neutron etc., are incredibly scarce. The ultimate goal is to understand the origin of uranium. The nuclei along the pathway to uranium in the r-process are in "Terra Incognita". In principle, as many of these nuclides have more neutrons than 238U, this region is inaccessible via the in-flight fragmentation reactions and in-flight fission reactions used at the present major facilities worldwide. Therefore, the multi-nucleon transfer (MNT) reaction, which has been studied at the KEK Isotope Separation System (KISS), is attracting attention. However, in contrast to in-flight fission and fragmentation, the nuclei produced by the MNT reaction have characteristic kinematics with broad angular distribution and relatively low energies which makes them non-amenable to in-flight separation techniques. KISS-II would be the first facility to effectively connect production, separation, and analysis of nuclides along the r-process path leading to uranium. This will be accomplished by the use of a large solenoid to collect MNT products while rejecting the intense primary beam, a large helium gas catcher to thermalize the MNT products, and an MRTOF mass spectrograph to perform mass analysis and isobaric purification of subsequent spectroscopic studies. The facility will finally allow us to explore the neutron-rich nuclides in this Terra Incognita.Comment: Editors: Yutaka Watanabe and Yoshikazu Hirayam

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

京都府下丹後地方の柑橘園土壌の一般理化学的性質と葉成分について(農芸化学部門)

京都府下丹後地方の柑橘園土壌の一般理化学的性質および葉成分について分析し, 今後の当地方の柑橘栽培における土壌, 肥培管理の基礎資料をえた。すなわち丹後地方の柑橘園土壌は植物栄養的に母材をほぼ同じくする近畿, 中国地方の主産地土壌にくらべてせき薄な土壌地帯であり, 葉分析より診断される柑橘の栄養状態も良好とはいえず, とくに微量要素の欠乏に注意すべきことを明らかにした。The chemical and physical properties of soils and the inorganic compositions of leaves in the citrus gardens in Tango District, Kyoto Prefecture, were studied and the following results were obtained. The citrus garden soils in Tango District, which were formed on granite and palezoic shale, showed lower fertility level than the soils which were formed on the same parent materials in the citrus growing parts of Wakayama, Mie, Hiroshima and Yamaguchi Prefecture. The nutritional status of citrus were not so good and especially the trace element status in both soils and plants were very bad, for example, the manganese and zinc defficiency had appeared

Isolation and Characterization of Endophyte Bacillus velezensis KOF112 from Grapevine Shoot Xylem as Biological Control Agent for Fungal Diseases

As the use of chemical fungicides has raised environmental concerns, biological control agents have attracted interest as an alternative to chemical fungicides for plant-disease control. In this study, we attempted to explore biological control agents for three fungal phytopathogens causing downy mildew, gray mold, and ripe rot in grapevines, which are derived from shoot xylem of grapevines. KOF112, which was isolated from the Japanese indigenous wine grape Vitis sp. cv. Koshu, inhibited mycelial growth of Botrytis cinerea, Colletotrichum gloeosporioides, and Phytophthora infestans. The KOF112-inhibited mycelial tips were swollen or ruptured, suggesting that KOF112 produces antifungal substances. Analysis of the 16S rDNA sequence revealed that KOF112 is a strain of Bacillus velezensis. Comparative genome analysis indicated significant differences in the synthesis of non-ribosomal synthesized antimicrobial peptides and polyketides between KOF112 and the antagonistic B. velezensis FZB42. KOF112 showed biocontrol activities against gray mold caused by B. cinerea, anthracnose by C. gloeosporioides, and downy mildew by Plasmopara viticola. In the KOF112–P. viticola interaction, KOF112 inhibited zoospore release from P. viticola zoosporangia but not zoospore germination. In addition, KOF112 drastically upregulated the expression of genes encoding class IV chitinase and β-1,3-glucanase in grape leaves, suggesting that KOF112 also works as a biotic elicitor in grapevine. Because it is considered that endophytic KOF112 can colonize well in and/or on grapevine, KOF112 may contribute to pest-management strategies in viticulture and potentially reduce the frequency of chemical fungicide application

cGMP dynamics underlie thermosensation in C. elegans

Animals sense ambient temperature so that they can adjust their behavior to the environment; they avoid noxious heat and coldness and stay within a survivable temperature range. C. elegans can sense temperature, memorize past cultivation temperature and navigate towards preferable temperature, for which a thermosensory neuron, AFD, is essential. AFD responds to temperature increase from the past cultivation temperature by increasing intracellular Ca2+ level. We aimed to reveal how AFD encodes and memorizes the information of temperature. Although cGMP synthesis is crucial for thermosensation by AFD, whether and how cGMP level temporally fluctuates in AFD remained elusive. We therefore monitored cGMP level in AFD and found that cGMP dynamically responded to temperature change in a manner dependent on past cultivation temperature. Given that cGMP dynamics is supposed to be upstream of Ca2+ dynamics, our results suggest that AFD’s memory is formed by simpler molecular mechanisms than previously expected from the Ca2+ dynamics. Moreover, we analyzed how guanylyl cyclases and phosphodiesterases, which synthesize and degrade cGMP, respectively, contributed to cGMP and Ca2+ dynamics and thermotaxis behavior