Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy

ObjectivesWe sought to explore the relationship between a Tcap gene (TCAP)abnormality and cardiomyopathy.BackgroundHypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc.MethodsThe TCAPwas analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays—yeast two-hybrid and glutathion S-transferase pull-down competition—were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q.ResultsTwo TCAPmutations, T137I and R153H, were found in patients with HCM, and another TCAPmutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1.ConclusionsThese observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components

Secondary EML4?ALK-positive Lung Adenocarcinoma in a Patient Previously Treated for Acute Lymphoblastic Leukemia in Childhood: A Case Reportated for Acute Lymphoblastic Leukemia in Childhood: A Case Report

It is widely recognized that the risk of secondary neoplasms increases as childhood cancer survivors progress through adulthood. These are mainly hematological malignancies, and recurrent chromosome translocations are commonly detected in such cases. On the other hand, while secondary epithelial malignancies have sometimes been reported, chromosome translocations in these epithelial malignancies have not. A 33-year-old man who had been diagnosed with acute lymphoblastic leukemia and treated with chemotherapy almost 20 years earlier was diagnosed with lung adenocarcinoma. After chromosomal rearrangement of echinoderm microtubule- associated protein-like 4 gene and the anaplastic lymphoma kinase gene was detected in this adenocarcinoma, he responded to treatment with crizotinib. It was therefore concluded that this echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene-positive lung adenocarcinoma was a secondary epithelial malignancy

Reduced Rate of Neural Differentiation in the Dentate Gyrus of Adult Dysbindin Null (Sandy) Mouse

Genetic variations in the gene encoding dysbindin has consistently been associated with schizophrenia and bipolar disorder, although little is known about the neural functions carried out by dysbindin. To gain some insight into this area, we took advantage of the readily available dysbindin-null mouse sandy (sdy−/−) and studied hippocampal neurogenesis using thymidine analogue bromodeoxuridine (BrdU). No significant differences were found in the proliferation (4 hours) or survival (1, 4 and 8 weeks after the last BrdU injection) of progenitors in the subgranular regions of the dentate gyrus between sdy−/− and sdy+/+ (control) mice. However, 4 weeks after the last BrdU injection, a significant reduction was observed in the ratio of neuronal differentiation in sdy−/− when compared to that of sdy+/+ (sdy+/+  = 87.0±5.3% vs. sdy−/−  = 71.3±8.3%, p = 0.01). These findings suggest that dysbindin plays a role during differentiation process in the adult hippocampal neurogenesis and that its deficit may negatively affect neurogenesis-related functions such as cognition and mood

Isotope production in proton-, deuteron-, and carbon-induced reactions on Nb 93 at 113 MeV/nucleon

Isotope-production cross sections for p-, d-, and C-induced spallation reactions on Nb93 at 113 MeV/nucleon were measured using the inverse-kinematics method employing secondary targets of CH2, CD2, and C. The measured cross sections for Mo90, Nb90, Y86,88 produced by p-induced reactions were found to be consistent with those measured by the conventional activation method. We performed benchmark tests of the reaction models INCL-4.6, JQMD, and JQMD-2.0 implemented in the Particle and Heavy Ion Transport code System (PHITS) and of the nuclear data libraries JENDL-4.0/HE, TENDL-2017, and ENDF/B-VIII.0. The model calculations also showed generally good agreement with the measured isotope-production cross sections for p-, d-, and C-induced reactions. It also turns out that, among the three nuclear data libraries, JENDL-4.0/HE provides the best agreement with the measured data for the p-induced reactions. We compared the present Nb93 data with the Zr93 data, that were measured previously by the same inverse kinematics method (Kawase et al., Prog. Theor. Exp. Phys. 2017, 093D03 (2017)2050-391110.1093/ptep/ptx110), with particular attention to the effect of neutron-shell closure on isotope production in p- and d-induced spallation reactions. The isotopic distributions of the measured production cross sections in the Zr93 data showed noticeable jumps at neutron number N=50 in the isotopic chains of ΔZ=0 and -1, whereas no such jump appeared in isotopic chain of ΔZ=0 in the Nb93 data. From INCL-4.6 + GEM calculations, we found that the jump formed in the evaporation process is smeared out by the intranuclear cascade component in Nb91 produced by the Nb93(p,p2n) and (d,d2n) reactions on Nb93. Moreover, for Nb93, the distribution of the element-production cross sections as a function of the change in proton number ΔZ is shifted to smaller ΔZ than for Zr93, because the excited Nb prefragments generated by the cascade process are more likely to emit protons than the excited Zr prefragments, due to the smaller proton-separation energies of the Nb isotopes

Coulomb breakup reactions of 93,94 Zr in inverse kinematics

Coulomb breakup reactions of 93,94 Zr have been studied in inverse kinematics at incident beam energies of about 200 MeV/nucleon in order to evaluate neutron capture reaction methods. The 93 Zr(n,γ) 94 Zr reaction is particularly important as a candidate nuclear transmutation reaction for the long-lived fission product 93 Zr in nuclear power plants. One- and two-neutron removal cross sections on Pb and C targets were measured to deduce the inclusive Coulomb breakup cross sections, 375 ± 29 (stat.) ± 30 (syst.) and 403 ± 26 (stat.) ± 31 (syst.) mb for 93 Zr and 94 Zr, respectively. The results are compared with estimates using the standard Lorentzian model and microscopic calculations. The results reveal a possible contribution of the pygmy dipole resonance or giant quadrupole resonance in the Coulomb breakup reactions of 94 Zr

サンカ ストレス ニヨリ ユウドウ サレル ナイブンピツ キノウ ヘンカ ニ タイスル ショウジュセン ノ エイキョウ

活性酸素種は老化を始めとして,糖尿病,発癌,アテローム硬化症などの生活習慣病の発症と深くかかわっていると考えられている.さらに,活性酸素種により内分泌障害も生じる可能性がある.一方,抗酸化物質は活性酸素種により引き起こされる様々な障害を予防することが知られている.我々は一般医薬品である松寿仙が強力な抗酸化活性を持つことをすでに示している.今回は,生体内でヒドロキシルラジカルを産生するferric nitrilotriacetate (FeNTA)により誘導される内分泌系の変化を松寿仙が保護するかどうかを調べることを目的にしてこの実験を行った.7週齢のWistar系雄ラットに飲料水に12.5%に含まれる松寿仙を12日間投与し, FeNTA (Fe, 7.5mg/kg)を腹腔内注射し, 12時間後に実験を行った.血中テストステロンはFeNTA投与により急速に低下したが,松寿仙前投与によりその低下が抑えられた.血中チロキシン値はFeNTAで低下したが,松寿仙はそれを正常化した.血中トリヨードチロニン値はFeNTAによっても松寿仙によっても何ら影響を受けなかった.血中コルチコステロンはFeNTAにより著しく増加したが,松寿仙はそれを正常化した.副腎のアスコルビン酸はFeNTAにより減少し,松寿仙により正常に復した.アスパラギン酸アミノ基転移酵素とアラニンアミノ基転移酵素および血清クレアチニンと尿素窒素はFeNTAにより上昇したが,松寿仙によりこれらの上昇はいずれにも正常とほぼ同じレベルまで戻った.以上の結果は,松寿仙はその中に含まれる生薬成分の抗酸化作用によりFeNTAで引き起こされた内分泌機能変化を保護することを示すものと考えられる.Reactive oxygen species (ROS) are involved in pathogenesis of various diseases, including senescence, diabetes mellitus, carcinoma and atherosclerosis. Endocrine disorders may also be induced by ROS. Antioxidants such as vitamin E and ascorbic acid have been shown to delay or prevent a variety of injuries caused by ROS. Our previous studies have shown that Shojusen acts as potent antioxidant in ROS-mediated disorders. The aim of our present study is to examine if Shojusen protects endocrine disturbances induced by ferric nitrilotriacetate (FeNTA) that generates hydroxyl radicals in vivo. Wistar rats of 7-week old were treated with or without 12.5 % Shojusen in drinking water for 12 d and FeNTA (7.5 mg/kg) was injected intraperitoneally 12 h before experiments. Serum testosterone decreased rapidly after FeNTA treatment, while Shojusen pretreatment prevented this fall in testosterone levels. Serum T_4 levels were decreased by FeNTA, while Shojusen restored the decreased levels to normal. Serum T_3 levels remained unchanged either by FeNTA or Shojusen. Serum corticosterone levels increased significantly following FeNTA treatment, while Shojusen reduced the increase levels to normal. Adrenal ascorbic acid was decreased by FeNTA and restored to normal by Shojusen. Serum levels of aminotransferases, creatinine and urea nitrogen were increased by FeNTA, while these parameters was normalized in Shojusen-pretreated rats. These results show that Shojusen prevents hydroxyl radical-mediated endocrine disorders induced by FeNTA by acting as an antioxidant

Cross sections for nuclide production in proton- and deuteron-induced reactions on 93

Isotopic production cross sections were measured for proton- and deuteron-induced reactions on 93Nb by means of the inverse kinematics method at RIKEN Radioactive Isotope Beam Factory. The measured production cross sections of residual nuclei in the reaction 93Nb + p at 113 MeV/u were compared with previous data measured by the conventional activation method in the proton energy range between 46 and 249 MeV. The present inverse kinematics data of four reaction products (90Mo, 90Nb, 88Y, and 86Y) were in good agreement with the data of activation measurement. Also, the model calculations with PHITS describing the intra-nuclear cascade and evaporation processes generally well reproduced the measured isotopic production cross sections

Spallation reaction study for fission products in nuclear waste: Cross section measurements for 137

Spallation reactions for the long-lived fission products 137Cs, 90Sr and 107Pd have been studied for the purpose of nuclear waste transmutation. The cross sections on the proton- and deuteron-induced spallation were obtained in inverse kinematics at the RIKEN Radioactive Isotope Beam Factory. Both the target and energy dependences of cross sections have been investigated systematically. and the cross-section differences between the proton and deuteron are found to be larger for lighter fragments. The experimental data are compared with the SPACS semi-empirical parameterization and the PHITS calculations including both the intra-nuclear cascade and evaporation processes

Polyamine Distribution Patterns in Pseudomonas, Alcaligenes and Comamonas

Pseudomonas cepacia as well as all five Alcaligenes and three Comamonas species tested belonging to the beta subclass of Proteobacteria ubiquitously contained 2-hydroxyputrescine and putrescine as the major polyamines. Cadaverine was found in P. cepacia. Putrescine and spermidine were the major polyamines of Pseudomonas aeruginosa and Pseudomonas putida belonging to the gamma subclass and Pseudomonas saccharophila whose taxonomic positions have not been established. Polyamine distribution profiles can serve as a chemotaxonomic marker within Pseudomonas species. Relative distribution patterns of the major polyamines of P. aeruginosa did not changed at different culture periods in spite of increase or decrease of their levels during growth