Biomedical subjects

Y Noda

Publications and source records attributed to Y Noda.

At least 19 recordsLinked to original sources

PubMed2006

Collinear to spiral spin transformation without changing the modulation wavelength upon ferroelectric transition in Tb1-xDyxMnO3.

Lattice modulation and magnetic structures in magnetoelectric compounds Tb1-xDyxMnO3 have been studied around the ferroelectric (FE) Curie temperature TC by x-ray and neutron diffraction. Temperature-independent modulation vectors through TC are observed for the compounds with 0.50 <or=x<or=0.68. This indicates that ferroelectricity with a polarization (P) along the c axis in the RMnO3 series cannot be ascribed to such an incommensurate-commensurate transition of an antiferromagnetic order as was previously anticipated. A neutron diffraction study with x=0.59 shows that the FE transition is accompanied by the transformation of the Mn-spin alignment from sinusoidal (collinear) antiferromagnetism into a transverse-spiral structure. The observed spiral structure below TC is expected to produce P along the c axis with the "inverse" Dzialoshinski-Moriya interaction, which is consistent with observation.

Journal Article↗

PubMed2006

Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules.

The renin-angiotensin system in the kidney plays a critical role in the regulation of renal hemodynamics and sodium handling through the activation of vascular, glomerular and tubular angiotensin II type 1 (AT1) receptor-mediated signaling. We previously cloned a molecule that specifically bound to the AT1 receptor and modulated AT1 receptor signaling in vitro, which we named ATRAP (for AT1 receptor-associated protein). The purpose of this study is to analyze the renal distribution of ATRAP and to examine whether ATRAP is co-expressed with the AT1 receptor in the mouse kidney. We performed in situ hybridization, Western blot analysis, and immunohistochemistry to investigate the expression of ATRAP mRNA and protein in the mouse kidney. The results of Western blot analysis revealed the ATRAP protein to be abundantly expressed in the kidney. Employing in situ hybridization and immunohistochemistry, we found that both ATRAP mRNA and the protein were widely distributed along the renal tubules from Bowman's capsules to the inner medullary collecting ducts. ATRAP mRNA was also detected in the glomeruli, vasculature, and interstitial cells. In all tubular cells, the ATRAP protein colocalized with the AT1 receptor. Finally, we found that the dietary salt depletion significantly decreased the renal expression of ATRAP as well as AT1 receptor. These findings show ATRAP to be abundantly and broadly distributed in nephron segments where the AT1 receptor is expressed. Furthermore, this is the first report demonstrating a substantial colocalization of ATRAP and AT1 receptor in vivo.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes.

There is no established genetic model of bipolar disorder or major depression, which hampers research of these mood disorders. Although mood disorders are multifactorial diseases, they are sometimes manifested by one of pleiotropic effects of a single major gene defect. We focused on chronic progressive external ophthalmoplegia (CPEO), patients with which sometimes have comorbid mood disorders. Chronic progressive external ophthalmoplegia is a mitochondrial disease, which is accompanied by accumulation of mitochondrial DNA (mtDNA) deletions caused by mutations in nuclear-encoded genes such as POLG (mtDNA polymerase). We generated transgenic mice, in which mutant POLG was expressed in a neuron-specific manner. The mice showed forebrain-specific defects of mtDNA and had altered monoaminergic functions in the brain. The mutant mice exhibited characteristic behavioral phenotypes, a distorted day-night rhythm and a robust periodic activity pattern associated with estrous cycle. These abnormal behaviors resembling mood disorder were worsened by tricyclic antidepressant treatment and improved by lithium, a mood stabilizer. We also observed antidepressant-induced mania-like behavior and long-lasting irregularity of activity in some mutant animals. Our data suggest that accumulation of mtDNA defects in brain caused mood disorder-like mental symptoms with similar treatment responses to bipolar disorder. These findings are compatible with mitochondrial dysfunction hypothesis of bipolar disorder.

Animals↗

PubMed2005

An organic thyristor.

Thyristors are a class of nonlinear electronic device that exhibit bistable resistance--that is, they can be switched between two different conductance states. Thyristors are widely used as inverters (direct to alternating current converters) and for the smooth control of power in a variety of applications such as motors and refrigerators. Materials and structures that exhibit nonlinear resistance of this sort are not only useful for practical applications: they also provide systems for exploring fundamental aspects of solid-state and statistical physics. Here we report the discovery of a giant nonlinear resistance effect in the conducting organic salt theta-(BEDT-TTF)2CsCo(SCN)4, the voltage-current characteristics of which are essentially the same as those of a conventional thyristor. This intrinsic organic thyristor works as an inverter, generating an alternating current when a static direct-current voltage is applied. Whereas conventional thyristors consist of a series of diodes (their nonlinearity comes from interface effects at the p-n junctions), the present salt exhibits giant nonlinear resistance as a bulk phenomenon. We attribute the origin of this effect to the current-induced melting of insulating charge-order domains, an intrinsically non-equilibrium phenomenon in the sense that ordered domains are melted by a steady flow.

Journal Article↗

PubMed2004

Successful intrauterine treatment with radiofrequency ablation in a case of acardiac twin pregnancy complicated with a hydropic pump twin.

Twin reversed arterial perfusion sequence is a serious complication of monochorionic twin pregnancy, as the pump twin that perfuses blood to the acardiac twin may experience heart failure and fetal hydrops resulting in a poor perinatal outcome. A woman with an acardiac twin pregnancy complicated by a hydropic pump twin underwent intrauterine treatment with radiofrequency ablation (RFA) at 27 weeks of gestation. Obliteration of blood flow to the acardiac twin from the pump twin was successful. Fetal hydrops resolved by the time of delivery at 32 weeks of gestation, in spite of transient deterioration, and a good postnatal outcome was achieved for the pump twin. We found that RFA was an effective intrauterine treatment for acardiac twin pregnancy and suggest that it could be introduced in cases complicated by a hydropic pump twin.

Adult↗

PubMed2003

Mutations that are synthetically lethal with a gas1Delta allele cause defects in the cell wall of Saccharomyces cerevisiae.

The GAS1-related genes of fungi encode GPI-anchored proteins with beta-1,3-glucanosyltransferase activity. Loss of this activity results in defects in the assembly of the cell wall. We isolated mutants that show a synthetic defect when combined with a gas1Delta allele in Saccharomyces cerevisiae, and identified nine wild-type genes that rescue this defect. The indispensability of BIG1 and KRE6 for the viability of gas1Delta cells confirmed the important role of beta-1,6-glucan in cells that are defective in the processing of beta-1,3-glucan. The identification of the Wsc1p hypo-osmotic stress sensor and components of the PKC signal transduction pathway in our screen also confirmed that the cell wall integrity response attenuates the otherwise lethal gas1Delta defect. Unexpectedly, we found that the KEX2 gene is also required for the viability of the gas1Delta mutant. Kex2p is a Golgi/endosome-membrane-anchored protease that processes secretory preproteins. A cell wall defect was also found in the kex2Delta mutant, which was suppressible by multiple copies of the MKC7 or YAP3 gene, both of which encode other GPI-anchored proteases. Therefore, normal cell wall assembly requires proteolytic processing of secretory preproteins. Furthermore, the genes CSG2 and IPT1 were found to be required for normal growth of gas1Delta cells in the presence of 1 M sorbitol. This finding suggests that complex sphingolipids play a role in the hyper-osmotic response.

Cell Wall↗

PubMed2003

Effect of AD-5423 on animal models of schizophrenia: phencyclidine-induced behavioral changes in mice.

The antipsychotic efficacy of AD-5423, which has the properties of both a serotonin 5-HT(2) and a dopamine D(2) receptor antagonist, was evaluated using animal models of schizophrenia. Sensitization to phencyclidine (PCP)-induced hyperlocomotion is considered a model of the positive symptoms of schizophrenia, and was significantly antagonized by AD-5423 and haloperidol. The PCP-induced enhancement of immobility induced by the forced swimming test, a model of the negative symptoms of schizophrenia, was attenuated by AD-5423 but not by haloperidol. Since this attenuated effect of AD-5423 was antagonized by DOI, a serotonin 5-HT(2) receptor agonist, it is postulated to be mediated by serotonin 5-HT(2) receptors. These findings suggest that AD-5423 would be clinically effective against both the positive and negative symptoms of schizophrenia.

Animals↗

PubMed2003

Neuronal mechanism of nociceptin-induced modulation of learning and memory: involvement of N-methyl-D-aspartate receptors.

Nociceptin (also called orphanin FQ) is an endogenous heptadecapeptide that activates the opioid receptor-like 1 (ORL1) receptor. Nociceptin system not only affects the nociception and locomotor activity, but also regulates learning and memory in rodents. We have previously reported that long-term potentiation and memory of ORL1 receptor knockout mice are enhanced compared with those in wild-type mice. Here, we show the neuronal mechanism of nociceptin-induced modulation of learning and memory. Retention of fear-conditioned contextual memory was significantly enhanced in the ORL1 receptor knockout mice without any changes in cued conditioned freezing. Inversely, in the wild-type mice retention of contextual, but not cued, conditioning freezing behavior was suppressed by exogenous nociceptin when it was administered into the cerebroventricle immediately after the training. ORL1 receptor knockout mice exhibited a hyperfunction of N-methyl-D-aspartate (NMDA) receptor, as evidenced by an increase in [3H]MK-801 binding, NMDA-evoked 45Ca2+ uptake and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity and its phosphorylation as compared with those in wild-type mice. The NMDA-induced CaMKII activation in the hippocampal slices of wild-type mice was significantly inhibited by exogenous nociceptin via a pertussis toxin-sensitive pathway. However, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor GluR1 subunit at Ser831 and Ser845, and NMDA receptor subunit NR2B at Thr286 were phosphorylated similarly after NMDA receptor stimulation in both type of mice. The expressions of GluR1 and GluR2 also did not change, but the levels of polysialylated form of neuronal cell adhesion molecule (N-CAM) were reduced in the ORL1 receptor knockout as compared with wild-type mice. These results suggest that nociceptin system negatively modulates learning and memory through the regulation of NMDA receptor function and the expression of N-CAM.

Animals↗

PubMed2002

Adaptive response and the influence of ageing: effects of low-dose irradiation on cell growth of cultured glial cells.

PURPOSE: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of ageing on the response. MATERIALS AND METHODS: Glial cells were cultured from young and older rats (1 and 24 months). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signalling pathway factors in RAR was investigated using their inhibitors, activators, and mutated and knockout glial cells. RESULTS: RAR was observed in cells cultured from young rats but was not in cells from older animals. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low-dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia mutated (Atm) knockout mice showed no RAR. CONCLUSION: The results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with ageing.

Age Factors↗

PubMed2002

Personality, social support, coping and emotional distress after repeated spontaneous abortions.

Systematic investigations on the emotional impacts of repeated spontaneous abortions have been few. We mounted a prospective study of a cohort of couples who had experienced two consecutive first trimester spontaneous abortions and for whom no clearly identifiable causes were found. The present report is based on the first part of the study and examines: (1) emotional distress reported by the miscarrying women at six months (median, range 1-12 months) after two abortions; and (2) psychosocial predictors influencing such distress. The mean score of the women on the Symptom Checklist 90-Revised--one of the most popular self-report scales for psychopathology--was 0.38, whereas that for the general population is reported to be 0.26 (the higher the score, the more psychopathology). Fourteen percent of the cohort scored above the cutoff point for mental disorders screening. Factors examined and found non-influential upon the level of emotional distress include: the maternal age; whether the last pregnancy was planned and wished for or not; and coping styles of the women after the abortions. Control by the husbands over the marital relationship and neurotic personality traits of the women increased the emotional distress, whereas the social support the women perceive decreased it. These findings suggest that martial and social support are important in determining the level of psychiatric morbidity after repeated abortions.

Abortion, Spontaneous↗

PubMed2001

KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIb-associated Triton-insoluble membranes.

We have identified and characterized a COOH-terminal motor domain-type kinesin superfamily protein (KIFC), KIFC3, in the kidney. KIFC3 is a minus end-directed microtubule motor protein, therefore it accumulates in regions where minus ends of microtubules assemble. In polarized epithelial cells, KIFC3 is localized on membrane organelles immediately beneath the apical plasma membrane of renal tubular epithelial cells in vivo and polarized MDCK II cells in vitro. Flotation assay, coupled with detergent extraction, demonstrated that KIFC3 is associated with Triton X-100-insoluble membrane organelles, and that it overlaps with apically transported TGN-derived vesicles. This was confirmed by immunoprecipitation and by GST pulldown experiments showing the specific colocalization of KIFC3 and annexin XIIIb, a previously characterized membrane protein for apically transported vesicles (Lafont, F., S. Lecat, P. Verkade, and K. Simons. 1998. J. Cell Biol. 142:1413-1427). Furthermore, we proved that the apical transport of both influenza hemagglutinin and annexin XIIIb was partially inhibited or accelerated by overexpression of motor-domainless (dominant negative) or full-length KIFC3, respectively. Absence of cytoplasmic dynein on these annexin XIIIb-associated vesicles and distinct distribution of the two motors on the EM level verified the existence of KIFC3-driven transport in epithelial cells.

Amino Acid Sequence↗

PubMed2001

Enhancement of immobility induced by repeated phencyclidine injection: association with c-Fos protein in the mouse brain.

Immunohistochemistry of c-Fos protein was performed to study changes in neuronal activity in discrete brain areas of mice repeatedly treated with phencyclidine (PCP) showing enhancement of immobility in the forced swimming test, this behavioral change being considered as avolition, which is one of negative symptoms of schizophrenia. Repeated treatment with PCP significantly prolonged immobility time in the forced swimming test, compared with saline treatment. The c-Fos protein expression of mice showing PCP-induced enhancement of immobility was increased in certain brain regions, such as the retrosplenial cortex, pyriform cortices, pontine nuclei, cingulate, frontal cortex and thalamus, compared with that of PCP-treated, non-swimming and saline-treated, swimming groups. These results suggest that increased c-Fos protein is involved in the expression of PCP-induced enhancement of immobility, and c-Fos expression plays a role in negative symptoms-like behavioral changes.

Animals↗

PubMed2001

"Devil's staircase"-type phase transition in NaV2O5 under high pressure.

The "devil's staircase"-type phase transition in the quarter-filled spin-ladder compound NaV2O5 has been discovered at low temperature and high pressure by synchrotron radiation x-ray diffraction. A large number of transitions are found to successively take place among higher-order commensurate phases with 2a x 2b x zc type superstructures. The observed temperature and pressure dependence of modulation wave number q(c), defined by 1/z, is well reproduced by the axial next nearest neighbor Ising model. The q(c) is suggested to reflect atomic displacements presumably coupled with charge ordering in this system.

Journal Article↗

PubMed2001

Structure and ligand recognition of the PB1 domain: a novel protein module binding to the PC motif.

PB1 domains are novel protein modules capable of binding to target proteins that contain PC motifs. We report here the NMR structure and ligand-binding site of the PB1 domain of the cell polarity establishment protein, Bem1p. In addition, we identify the topology of the PC motif-containing region of Cdc24p by NMR, another cell polarity establishment protein that interacts with Bem1p. The PC motif-containing region is a structural domain offering a scaffold to the PC motif. The chemical shift perturbation experiment and the mutagenesis study show that the PC motif is a major structural element that binds to the PB1 domain. A structural database search reveals close similarity between the Bem1p PB1 domain and the c-Raf1 Ras-binding domain. However, these domains are functionally distinct from each other.

Adaptor Proteins, Signal Transducing↗

PubMed2001

XANES study of charge ordering on the spin-Peierls phase transition of alpha'-NAV2O5.

alpha'-NaV2O5 transforms at Tc = 34K, and the origin of the phase transition seems to be caused by the charge order and spin-Peierls mechanism. However the experiments which reveal the existence of charge order are very little. We measured XANES of V atoms which relates to the valence of V. It was found that the valences of V atoms in NaV2O5 were V4.5+ in the high temperature phase by comparing pre-edge and XANES of NaV2O5 with that of LiV2O5 CaV2O5 and V2O5. The analysis of EXAFS also shows the environment of the V4.5+ state.

Journal Article↗

PubMed2001

Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-D-aspartate receptor-ion channel complex, not via sigma(1) receptors.

The effects of several N-methyl-D-aspartate (NMDA) receptor- and sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA receptor antagonist, dizocilpine (0.2 mg/kg, i.p.) and a putative sigma(1) receptor agonist, (+)-SKF-10047 (10 mg/kg, i.p.) fully substituted for PCP in every rat tested. Neither a competitive NMDA receptor antagonist, CGS-19755 (0.1-3 mg/kg, i.p.), sigma(1) receptor agonist, (+)-pentazocine (10-30 mg/kg, i.p.) nor dextromethorphan (10-20 mg/kg, i.p.) produced PCP-like discriminative stimulus effects. The discriminative stimulus effects of PCP (1.5 mg/kg, i.p.), dizocilpine (0.2 mg/kg, i.p.) and (+)-SKF-10047 (10 mg/kg, i.p.) were significantly attenuated by CGS-19755 (1 mg/kg, i.p.), but not by sigma(1) receptor antagonist BMY-14802 (10 mg/kg, i.p.) and NE-100 (5 mg/kg, i.p.). These results suggest that the discriminative stimulus effects of PCP are predominantly mediated via PCP binding sites on the NMDA receptor-ion channel complex, not via sigma(1) receptors. In addition, the PCP-like discriminative stimulus effects of (+)-SKF-10047 were demonstrated to be mediated via PCP binding sites.

Animals↗

PubMed2001

Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment.

Phencyclidine (PCP) reduced social behavior (SB) in a dose- and time-dependent fashion. However, no such SB deficit was observed on repeated treatment with methamphetamine for 14 days. The SB deficit produced by treatment with PCP (10 mg/kg/day) for 14 days, which persisted for 28 days after withdrawal, was attenuated by clozapine (10 mg/kg/day) given for 7 days, whereas haloperidol for 7 days had no effect. Clozapine, but not haloperidol, alone at the same treatment dose increased SB in saline-treated mice. These results suggest that the proposed PCP model in mice will provide a tool to test beneficial effects of atypical antipsychotics on social dysfunction in schizophrenia, and contribute to our understanding of the mechanisms by which clozapine improves SB deficit.

Animals↗

PubMed2001

Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking the NMDA receptor epsilon1 subunit.

NMDA receptors, an ionotropic subtype of glutamate receptors (GluRs) forming high Ca(2+)-permeable cation channels, are composed by assembly of the GluRzeta subunit (NR1) with any one of four GluRepsilon subunits (GluRepsilon1-4; NR2A-D). In the present study, we investigated neuronal functions in mice lacking the GluRepsilon1 subunit. GluRepsilon1 mutant mice exhibited a malfunction of NMDA receptors, as evidenced by alterations of [(3)H]MK-801 binding as well as (45)Ca(2+) uptake through the NMDA receptors. A postmortem brain analysis revealed that both dopamine and serotonin metabolism were increased in the frontal cortex and striatum of GluRepsilon1 mutant mice. The NMDA-stimulated [(3)H]dopamine release from the striatum was increased, whereas [(3)H]GABA release was markedly diminished in GluRepsilon1 mutant mice. When (+)bicuculline, a GABA(A) receptor antagonist, was added to the superfusion buffer, NMDA-stimulated [(3)H]dopamine release was significantly increased in wild-type, but not in the mutant mice. GluRepsilon1 mutant mice exhibited an increased spontaneous locomotor activity in a novel environment and an impairment of latent learning in a water-finding task. Hyperlocomotion in GluRepsilon1 mutant mice was attenuated by treatment with haloperidol and risperidone, both of which are clinically used antipsychotic drugs, at doses that had no effect in wild-type mice. These findings provide evidence that NMDA receptors are involved in the regulation of behavior through the modulation of dopaminergic and serotonergic neuronal systems. In addition, our findings suggest that GluRepsilon1 mutant mice are useful as an animal model of psychosis that is associated with NMDA receptor malfunction and hyperfunction of dopaminergic and serotonergic neuronal systems.

Animals↗