視覚野においてT型Ca²⁺チャネル依存性長期増強を引き起こすためにはTNFαが必要である

Monocular deprivation produces depression and potentiation of visual responses evoked in visual cortical neurons by stimulation of deprived and nondeprived eyes, respectively, during the critical period of ocular dominance plasticity. Our previous studies suggested that T-type Ca²⁺ channel-dependent long-term potentiation (LTP), induced by 2 Hz stimulation, mediates the potentiation of visual responses. However, it was proposed that the experience-dependent response potentiation is mediated by tumor necrosis factor-α (TNFα)-dependent homeostatic synaptic scaling but not by Hebbian synaptic plasticity, because the potentiation was absent in TNFα knockout (TNFα-KO) mice. In this study, we investigated whether TNFα is required for LTP induced by 2 Hz stimulation using visual cortical slices prepared from critical period mice and rats. The production of LTP was prevented by pharmacological blockade of TNFα in rats and mice. LTP production was also prevented by an inhibitor of TNFα-converting enzyme that converts membrane-bound TNFα to soluble TNFα. In TNFα-KO mice, LTP did not occur and was rescued by exogenous soluble TNFα. Soluble TNFα was required for LTP production only during a restricted time window soon after 2 Hz stimulation. These results strengthen the view that T-type Ca²⁺ channel-dependent LTP contributes to the potentiation of nondeprived eye responses following monocular deprivation.博士（医学）・乙第1401号・平成29年6月28日Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved

Monthly minodronate inhibits bone resorption to a greater extent than does monthly risedronate

AbstractAs a bisphosphonate, minodronate (MIN) is one of the strongest inhibitors of bone resorption. However, there have been no reports directly comparing the antiresorptive effects of monthly MIN with those of monthly risedronate (RIS). We enrolled 30 cases of osteoporosis (OP; 16 in the MIN group [mean age: 68.2 years] and 14 in the RIS group [mean age: 68.1 years]) to investigate the early effects of treatment by monthly MIN or RIS over a 4-month period using bone turnover marker values. Only female patients were enrolled to avoid gender bias. Urinary cross-linked N-telopeptide of type I collagen (NTX) before treatment and at 1, 2, and 4 months of therapy, as well as serum bone alkaline phosphatase and alkaline phosphatase before treatment and at 4 months afterwards, were evaluated. All bone turnover marker values were significantly decreased at 4 months in both groups. The changes in urinary NTX at the study end point for RIS and MIN were −30.1% and −63.1%, respectively. From 2 months of treatment, the antiresorptive effects on urinary NTX by MIN were significantly higher than those by RIS, indicating that MIN more immediately and strongly inhibited bone absorption. Thus, monthly MIN seems to suppress bone resorption faster and more strongly than RIS in OP treatment

Predominant Magnetic States in Hubbard Model on Anisotropic Triangular Lattices

Using an optimization variational Monte Carlo method, we study the half-filled-band Hubbard model on anisotropic triangular lattices, as a continuation of the preceding study [J. Phys. Soc. Jpn 75, 074707 (2006)]. We introduce two new trial states: (i) A coexisting state of (\pi,\pi)-antiferromagnetic (AF) and a d-wave singlet gaps, in which we allow for a band renormalization effect, and (ii) a state with an AF order of 120^\circ spin structure. In both states, a first-order metal-to-insulator transition occurs at smaller U/t than that of the pure d-wave state. In insulating regimes, magnetic orders always exist; an ordinary (\pi,\pi)-AF order survives up to t'/t\sim 0.9 (U/t=12), and a 120^\circ-AF order becomes dominant for t'/t \gsim 0.9. The regimes of the robust superconductor and of the nonmagnetic insulator the preceding study proposed give way to these magnetic domains.Comment: 11 pages, 14 figure

Variational Monte Carlo studies of a t-J model on an anisotropic triangular lattice

With the insulating phase of \kappa-(BEDT-TTF)_2X in mind, we study a t-J model on an anisotropic triangular lattice, where the hopping integral is t' in one of the three directions, using a variational Monte Carlo method. By changing the value of t'/t, we study the stability of superconducting (SC) states with d- and d+id-wave symmetries and of an antiferromagnetic (AF) state. As t'/t decreases from 1, the stable state immediately switches from the d+id wave to the d wave. The AF state is stabilized from the normal spin liquid state for t'/t\lsim 0.7 at half filling. We also take account of Nagaoka ferromagnetism and a phase separation.Comment: 4 pages, 3 figure

Hepatitis B virus strains of subgenotype A2 with an identical sequence spreading rapidly from the capital region to all over Japan in patients with acute hepatitis B

ObjectiveTo examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses.MethodsDuring 1991 through 2009, a sentinel surveillance was conducted in 28 national hospitals in a prospective cohort study. Genotypes of HBV were determined in 547 patients with acute hepatitis B. Nucleotide sequences in the preS1/S2/S gene of genotype A and B isolates were determined for phylogenetic analyses.ResultsHBV genotype A was detected in 137 (25% (accompanied by genotype G in one)) patients, B in 48 (9%), C in 359 (66%), and other genotypes in the remaining three (0.5%). HBV persisted in five with genotype A including the one accompanied by genotype G; another was co-infected with HIV type 1. The genotype was A in 4.8% of patients during 1991-1996, 29.3% during 1997-2002, and 50.0% during 2003-2008 in the capital region, as against 6.5%, 8.5% and 33.1%, respectively, in other regions. Of the 114 genotype A isolates, 13 (11.4%) were subgenotype A1, and 101 (88.6%) were A2, whereas of the 43 genotype B isolates, 10 (23.3%) were subgenotype B1, 28 (65.1%) were B2, two (4.7%) were B3, and three (7.0%) were B4. Sequences of 65 (64%) isolates of A2 were identical, as were three (23%) of A1, and five (18%) of B2, but none of the B1, B3 and B4 isolates shared a sequence.ConclusionsAcute infection with HBV of genotype A, subgenotype A2 in particular, appear to be increasing, mainly through sexual contact, and spreading from the capital region to other regions in Japan nationwide. Infection persisted in 4% of the patients with genotype A, and HBV strains with an identical sequence prevailed in subgenotype A2 infections. This study indicates the need for universal vaccination of young people to prevent increases in HBV infection in Japan

The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function

Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In Cnot3-depleted hearts, Atg7 expression was posttranscriptionally increased. Genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice. We further showed that in Cnot3-depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis

Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population

Background: Previous genome-wide association studies have evaluated the impact of common genetic variants and identified several non-HLA risk loci associated with autoimmune liver diseases. More recent genome-wide association studies and replication analyses reported an association between variants of the CARD10 polymorphism rs6000782 and risk of type 1 autoimmune hepatitis (AIH). In this case-control study, we genotyped 326 Japanese AIH patients and 214 control subjects. Results: Genomic DNA from 540 individuals of Japanese origin, including 326 patients with type-1 AIH and 214 healthy controls, was analyzed for two single nucleotide polymorphisms (SNPs) in the CARD10 gene. We selected CARD10 rs6000782 SNPs and genotyped these using PCR-RFLP method and direct sequencing. The Chi square test revealed that the rs6000782 variant alle (c) was not associated with the susceptibility for AIH in a Japanese population [p = 0.376, odds ratio (OR) 1.271, 95 % confidence interval (CI) 0.747-2.161] in an allele model. Our data also showed that CARD10 rs6000782 variants were not associated with AIH or with the clinical parameters of AIH. Conclusions: In this study we examined an association between rs6000782 SNPs in the CARD10 gene and type-1 AIH. Results showed no significant association of rs62000782 with type-1 AIH in a Japanese population. This study demonstrated no association between CARD10 rs6000782 variants and AIH in a Japanese population