De novo NSF mutations cause early infantile epileptic encephalopathy

N‐ethylmaleimide‐sensitive factor (NSF) plays a critical role in intracellular vesicle transport, which is essential for neurotransmitter release. Herein, we, for the first time, document human monogenic disease phenotype of de novo pathogenic variants in NSF, that is, epileptic encephalopathy of early infantile onset. When expressed in the developing eye of Drosophila, the mutant NSF severely affected eye development, while the wild‐type allele had no detectable effect under the same conditions. Our findings suggest that the two pathogenic variants exert a dominant negative effect. De novo heterozygous mutations in the NSF gene cause early infantile epileptic encephalopathy

Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver

Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction

Practical Study for Conservation of Giant Salamander Andrias japonicus in Toyosaka, Higashi-Hiroshima, Japan <Article>

オオサンショウウオAndrias japonicus は,日本の固有種であり国の特別天然記念物である。環境省のレッドリストでは絶滅危惧Ⅱ類(VU)に指定され,全国的に生息状況の悪化が危惧されている。東広島市豊栄町椋梨川においても,河川の人工化等によりその数が減少し,保護活動の担い手の高齢化に伴い,本種の生息状況に関する情報が極めて乏しい状況であった。そこで,本河川での本種の分布・生態を明らかにする野外調査を実施した。その結果,2011 年からの約2年間の調査で成体21個体と幼生10個体を確認し,本河川が本種の生息地であるだけでなく貴重な繁殖地であることを確認した。しかし,幼生を除けば全長60 - 86cm の大型個体しか確認されず,弱齢個体の個体群への新規加入が正常に起こっていない危険性も示唆された。本稿では,本河川における本種の現状が危機的であることを具体的に報告し,本種の保全にむけた持続的な活動の構築を目指した普及活動の成果と課題についても報告する。The giant salamander Andrias japonicas, which is endemic to Japan, is ranked as vulnerable. It is designated as a national special natural monument. Information on the giant salamander in Higashi-Hiroshima city is extremely scarce. To determine the current habitat of A. japonicas, we surveyed the Mukunashi River including areas where the giant salamander had lived in the past. Our surveys did find 21 adults and 10 larvae of A. japonicas within a two year period (from 2011 to 2013). However, we did not discover any young individuals of total length of 50 mm - 600 mm. This suggests that larval recruitment is not successful. This paper specifically reports that a critical situation exists for the giant salamander in the Mukunashi River in Higashi-Hiroshima City. And the publicity work aiming at conservation and its result are also reported

Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells

http://creativecommons.org/licenses/by/2.0/ PublisherBackground: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells. Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity. Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis

Human T-cell Leukemia Virus-1 Infection is Associated with Atherosclerosis as Measured by Carotid Intima-Media Thickness in Japanese Community-Dwelling Older People

The association between human T-cell leukemia virus-1 (HTLV-1) and atherosclerosis remains to be determined. This case?control study aimed to investigate this association as measured by carotid intima?media thickness (CIMT). HTLV-1 infection was positively associated with CIMT, independent of atherosclerotic risks

Present Status in the Development of 6 MeV Heavy Ion Beam Probe on LHD

In order to measure the potential in Large Helical Device (LHD), we have been developing a heavy ion beam probe (HIBP). For probing beam, gold beam is used, which is accelerated by a tandem accelerator up to the energy of 6 MeV. The experiments for calibration of beam orbit were done, and experimental results were compared with orbit calculations. The experimental results coincided fairly with the calculation results. After the calibration of the beam orbit, the potential in plasma was tried to measure with the HIBP. The experimental data showed positive potential in a neutral beam heating phase on the condition of ne ? 5 × 10^18 m^-3, and the increase of potential was observed when the additional electron cyclotron heating was applied to this plasma. The time constant for this increase was about a few tens ms, which was larger than a theoretical expectation. In the spatial position of sample volume, we might have an ambiguity in this experiment

Syntheses and Characterization of New Nickel Coordination Polymers with 4,4′-Dipyridylsulfide. Dynamic Rearrangements of One-Dimensional Chains Responding to External Stimuli: Temperature Variation and Guest Releases/Re-Inclusions

Crystal structures and dynamic rearrangements of one-dimensional coordination polymers with 4,4′-dipyridylsulfide (dps) have been studied. Reaction of Ni(NO3)2·6H2O with dps in EtOH yielded [Ni(dps)2(NO3)2] ·EtOH (1), which had channels filled with guest EtOH molecules among the four Ni(dps)2 chains. This coordination polymer reversibly transformed the channel structure responding to temperature variations. Immersion of 1 in m-xylene released guest EtOH molecules to yield a guest-free coordination polymer [Ni(dps)2(NO3)2] (2a), which was also obtained by treatment of Ni(NO3)2·6H2O with dps in MeOH. On the other hand, removal of the guest molecules from 1 upon heating at 130 °C under reduced pressure produced a guest-free coordination polymer [Ni(dps)2(NO3)2] (2b). Although the 2a and 2b guest-free coordination polymers have the same formula, they showed differences in the assembled structures of the one-dimensional chains. Exposure of 2b to EtOH vapor reproduced 1, while 2a did not convert to 1 in a similar reaction. Reaction of Ni(NO3)2·6H2O with dps in acetone provided [Ni(dps)(NO3)2(H2O)] ·Me2CO (4) with no channel structure. When MeOH or acetone was used as a reaction solvent, the [Ni(dps)2(NO3)2] · (guest molecule) type coordination polymer, which was observed in 1, was not formed. Nevertheless, the reaction of Ni(NO3)2·6H2O with dps in MeOH/acetone mixed solution produced [Ni(dps)2(NO3)2]·0.5(MeOH·acetone) (5), which has an isostructural Ni-dps framework to 1

トクシマシ イシカイ ガ ウンエイ スル トクシマシ チイキ ホウカツ シエン センター ノ トリクミ

The Tokushima City Integrated Community Care Support Center, a public institution responsible for the Long-Term Care Insurance and welfare administration of Tokushima City, has high business operations fair and neutrality. The only support center in Tokushima City has been entrusted to the Tokushima City Medical Association and is a large center unusual in Japan. We are working to cooperation with relevant organizations to support the medical and health, welfare and care of the community. We try to establish an Integrated Community Care system, as elderly can continue to live so long and dignified. We divided a daily living area of Tokushima City into four, and have placed the staff for each area. The current number of staff is ５４ people in total, including public health nurses, social workers, chief care managers, and so on. Number of consultations reaches ３６，０００ per year. Occasionally, we received over １６０ consultations a day. There are a wide variety of consultation contents such as Dementia and long-term care services, elder abuse and consumer damage. Because of Medical Association’s operation, we are able to easily construct cooperation with the healthcare and the long-time care system. Therefore, the all citizens of Tokushima City can receive standard services equally, fair, and neutrally. There is no regional disparity, there is no user of the enclosure. Because we have１４branches of the support center in the city, they can bring a high level convenience to the citizens. It seems necessary to focus on the development of four promotions for the future citizens, ① Enhancement of the center output ② Cooperation of the healthcare and the long-term care ③ Improvement of the area community care conference ④ Increase of measures against Dementia

Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 369

Summary Background Drugs that inhibit the renin-angiotensin-aldosterone system benefi t patients at risk for or with existing cardiovascular disease. However, evidence for this eff ect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was eff ective in Japanese patients with cardiovascular disease