Showing papers by "University of Tsukuba published in 1999"

Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain

Abstract: Transcription factor Nrf2 is essential for the antioxidant responsive element (ARE)-mediated induction of phase II detoxifying and oxidative stress enzyme genes. Detailed analysis of differential Nrf2 activity displayed in transfected cell lines ultimately led to the identification of a new protein, which we named Keap1, that suppresses Nrf2 transcriptional activity by specific binding to its evolutionarily conserved amino-terminal regulatory domain. The closest homolog of Keap1 is a Drosophila actin-binding protein called Kelch, implying that Keap1 might be a Nrf2 cytoplasmic effector. We then showed that electrophilic agents antagonize Keap1 inhibition of Nrf2 activity in vivo, allowing Nrf2 to traverse from the cytoplasm to the nucleus and potentiate the ARE response. We postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel Nrf2 nuclear shuttling mechanism. The activation of Nrf2 leads in turn to the induction of phase II enzyme and antioxidative stress genes in response to electrophiles and reactive oxygen species.

Electronic and magnetic properties of nanographite ribbons

Abstract: Electronic and magnetic properties of ribbon-shaped nanographite systems with zigzag and armchair edges in a magnetic field are investigated by using a tight-binding model. One of the most remarkable features of these systems is the appearance of edge states, strongly localized near zigzag edges. The edge state in a magnetic field, generating a rational fraction of the magnetic flux ( f5 p/q) in each hexagonal plaquette of the graphite plane, behaves like a zero-field edge state with q internal degrees of freedom. The orbital diamagnetic susceptibility strongly depends on the edge shapes. The reason is found in the analysis of the ring currents, which are very sensitive to the lattice topology near the edge. Moreover, the orbital diamagnetic susceptibility is scaled as a function of the temperature, Fermi energy, and ribbon width. Because the edge states lead to a sharp peak in the density of states at the Fermi level, the graphite ribbons with zigzag edges show Curie-like temperature dependence of the Pauli paramagnetic susceptibility. Hence, there is a crossover from hightemperature diamagnetic to low-temperature paramagnetic behavior in the magnetic susceptibility of nanographite ribbons with zigzag edges. @S0163-1829~99!02111-6#

Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems

Abstract: We determined the immunohistochemical distributions of orexin-A and orexin-B, hypothalamic peptides that function in the regulation of feeding behavior and energy homeostasis. Orexin-A and -B neurons were restricted to the lateral and posterior hypothalamus, whereas both orexin-A and -B nerve fibers projected widely into the olfactory bulb, cerebral cortex, thalamus, hypothalamus, and brainstem. Dense populations of orexin-containing fibers were present in the paraventricular thalamic nucleus, central gray, raphe nuclei, and locus coeruleus. Moderate numbers of these fibers were found in the olfactory bulb, insular, infralimbic and prelimbic cortex, amygdala, ventral, and dorsolateral parts of the suprachiasmatic nucleus, paraventricular nucleus except the lateral magnocellular division, arcuate nucleus, supramammillary nucleus, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Small numbers of orexin fibers were present in the perirhinal, motor and sensory cortex, hippocampus, and supraoptic nucleus, and a very small number in the lateral magnocellular division of the paraventricular nucleus. Intracerebroventricular injections of orexins induced c-fos expression in the paraventricular thalamic nucleus, locus coeruleus, arcuate nucleus, central gray, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of the vagus, suprachiasmatic nucleus, supraoptic nucleus, and paraventricular nucleus except the lateral magnocellular division. The unique neuronal distribution of orexins and their functional activation of neural circuits suggest specific complex roles of the peptides in autonomic and neuroendocrine control.

Pathophysiology of endothelin in the cardiovascular system

Abstract: In this article, we review the basic pharmacological and biochemical features of endothelin and the pathophysiological roles of endothelin in cardiovascular diseases. Development of receptor antagonists has accelerated the pace of investigations into the pathophysiological roles of endogenous endothelin-1 in various diseases, e.g. chronic heart failure, renal diseases, hypertension, cerebral vasospasm, and pulmonary hypertension. In chronic heart failure, the expression of endothelin-1 and its receptors in cardiomyocytes is increased, and treatment with an endothelin receptor antagonist improves survival and cardiac function. Endothelin receptor antagonists also improve other cardiovascular diseases. These results suggest that the interference with endothelin pathway either by receptor blockade or by inhibition of endothelin converting enzyme may provide novel therapeutic drugs strategies for multiple disease states.

Maternal Pumilio acts together with Nanos in germline development in Drosophila embryos.

Abstract: The maternal RNA-binding proteins Pumilio (Pum) and Nanos (Nos) act together to specify the abdomen in Drosophila embryos. Both proteins later accumulate in pole cells, the germline progenitors. Nos is required for pole cells to differentiate into functional germline. Here we show that Pum is also essential for germline development in embryos. First, a mutation in pum causes a defect in pole-cell migration into the gonads. Second, in such pole cells, the expression of a germline-specific marker (PZ198) is initiated prematurely. Finally, pum mutation causes premature mitosis in the migrating pole cells. We show that Pum inhibits pole-cell division by repressing translation of cyclin B messenger RNA. As these phenotypes are indistinguishable from those produced by nos mutation, we conclude that Pum acts together with Nos to regulate these germline-specific events.

Rice gibberellin-insensitive dwarf mutant gene Dwarf 1 encodes the α-subunit of GTP-binding protein

Abstract: A rice Dwarf 1 gene was identified by using a map-based cloning strategy. Its recessive mutant allele confers a dwarf phenotype. Linkage analysis revealed that a cDNA encoding the α-subunit of GTP-binding protein cosegregated with d1 in 3,185 d1 segregants. Southern hybridization analysis with this cDNA as a probe showed different band patterns in several d1 mutant lines. In at least four independent d1 mutants, no gene transcript was observed by Northern hybridization analysis. Sequencing analysis revealed that an 833-bp deletion had occurred in one of the mutant alleles, which resulted in an inability to express GTP-binding protein. A transgenic d1 mutant with GTP-binding protein gene restored the normal phenotype. We conclude that the rice Dwarf 1 gene encodes GTP-binding protein and that the protein plays an important role in plant growth and development. Because the d1 mutant is classified as gibberellin-insensitive, we suggest that the GTP-binding protein might be associated with gibberellin signal transduction.

First-principles study of edge states of H-terminated graphitic ribbons

Abstract: The existence of the edge states of single-layered H-terminated graphitic ribbons predicted by Nakada et al. [Phys. Rev. B 54, 17 954 (1996)] has been confirmed by first-principles calculations within the framework of the local-density approximation and the pseudopotentials. The edge states in cases of stacked ribbons have also been examined, and it has been found that the existence of the edge states is dependent on the stacking manner. This phenomenon can be understood from the electronic structures of $\mathrm{AA}$- and $\mathrm{AB}$-stacked bulk graphite.

Martensitic transformation and shape memory behavior in sputter-deposited TiNi-base thin films

Abstract: Since 1990, TiNi and TiNiX (X=Cu, Pd, Hf) thin films have been made by sputtering The motivation for fabricating sputter-deposited TiNi-base shape memory alloy thin films originates from the great demand for the development of powerful microactuators which can drive micromachines, because actuation force and displacement are greatest in shape memory alloys amongst many actuator materials Stable shape memory effect and superelasticity, which are equivalent to those of bulk alloys, have been achieved in the sputter-deposited TiNi thin films Narrow transformation temperature hysteresis and high transformation temperatures were also achieved in TiNiCu and TiNi(Pd or Hf) thin films, respectively In the meantime, unique microstructures consisting of nonequilibrium nanoscale precipitates and nonequilibrium compositions in the matrix have been found in Ti-rich TiNi thin films which were fabricated from amorphous condition by annealing at a considerably low temperature Several micromachining processes have been proposed to fabricate some prototypes of microactuators utilizing TiNi thin films The present paper will review the recent development of the above mentioned topics relating to sputter-deposited TiNi-base shape memory alloy thin films

Class of binary sequences with zero correlation zone

Abstract: Based on the idea of the zero correlation zone (ZCZ), a class of binary sequences with the defined ZCZ property is presented. The ZCZ spreading code sequences can be used in spread spectrum systems and CDMA systems to eliminate multipath and cochannel interference.

Regulatory mechanisms of cellular response to oxidative stress.

Abstract: An antioxidant responsive element (ARE) or electrophile responsive element (EpRE) mediates the transcriptional activation of genes encoding phase II drug metabolizing enzymes. The ARE consensus sequence shows high similarity to an erythroid gene regulatory element, and based on the observation, we have recently found that transcription factor Nrf2 is essential for the coordinate induction of phase II detoxifying enzymes. The expression of anti-oxidative stress enzyme genes is also regulated by Nrf2. Detailed analysis of the regulatory mechanisms of Nrf2 activity has ultimately led us to the identification of a new protein, which we have named Keap1, that suppresses Nrf2 activity by specific binding to its evolutionarily-conserved N-terminal Neh2 regulatory domain.

Motion analysis of cervical vertebrae during whiplash loading.

Abstract: STUDY DESIGN: The motion of each cervical vertebra during simulated rear-end car collisions was analyzed. OBJECTIVES: To clarify the mechanism of zygapophysial joint injury during whiplash loading. SUMMARY OF BACKGROUND DATA: The zygapophysial joint is the suspected origin of neck pain after rear-end car collision. However, no studies have been conducted on the mechanisms of zygapophysial joint injuries. METHODS: Ten healthy male volunteers participated in this study. Subjects sat on a sled that glided backward on inclined rails and crashed into a damper at 4 km/kr. The motion of the cervical spine was recorded using cineradiography. Each vertebra's rotational angle and the instantaneous axes of rotation of the C5-C6 motion segments were quantified. These measurements implemented the template method. RESULTS: There were three distinct patterns of cervical spine motion after impact. In the flexion-extension group, C6 rotated backward before the upper vertebrae in the early phase; thus, the cervical spine showed a flexion position (initial flexion). After C6 reached its maximum rotational angle, C5 was induced to extend. As upper motion segments went into flexion, and the lower segments into extension, the cervical spine took an S-shaped position. In this position, the C5-C6 motion segments showed an open-book motion with an upward-shifted instantaneous axis of rotation. CONCLUSIONS: The cervical spine is forced to move from the lower vertebrae during rear-end collisions. This motion completely differs from normal extension motion and is probably related to the injury mechanism. Language: en

Electronic Spectra and Their Relation to the ( π,π) Collective Mode in High- Tc Superconductors

Abstract: The photoemission line shape near (pi, 0) in Bi(2)Sr(2)CaCu(2)O(8+delta) below T(c) is characterized by a sharp peak, followed at higher energy by a dip and hump. We study the evolution of this line shape as a function of momentum, temperature, and doping. We find the hump scales with the peak and persists above T(c) in the pseudogap state. We present strong evidence that the peak-dip-hump structure arises from the interaction of electrons with a collective mode of wave vector (pi, pi). The inferred mode energy and its doping dependence agree well with a magnetic resonance observed by neutron scattering.

JNAS: Japanese speech corpus for large vocabulary continuous speech recognition research

Abstract: In this paper we present the first public Japanese speech corpus for large vocabulary continuous speech recognition (LVCSR) technology, which we have titled JNAS (Japanese Newspaper Article Sentences). We designed it to be comparable to the corpora used in the American and European LVCSR projects. The corpus contains speech recordings (60 h) and their orthographic transcriptions for 306 speakers (153 males and 153 females) reading excerpts from the newspaper's articles and phonetically balanced (PB) sentences. This corpus contains utterances of about 45, 000 sentences as a whole with each speaker reading about 150 sentences. JNAS is being distributed on 16 CD-ROMs.

Theory on Rates of Excitation-Energy Transfer between Molecular Aggregates through Distributed Transition Dipoles with Application to the Antenna System in Bacterial Photosynthesis

Abstract: It has often been observed in the light-harvesting antenna system of bacterial photosynthesis that excitation-energy transfer (EET) takes place very rapidly to or from a nearly (or completely) optically forbidden state. So far, the rate constant of EET has usually been calculated by Forster's formula, which regards EET as arising from the overlap integral between the luminescence spectrum of the excitation donor and the absorption spectrum of its acceptor. The observed EETs are much faster than expected from this formula, since the transition dipole as a whole nearly (or completely) vanishes in this state, giving a very small (or completely vanishing) Forster's overlap integral. We note in these EETs that at least one of the donor and acceptor is an aggregate of chromophores. Individual chromophores comprising the aggregate retain nonvanishing transition dipoles, even if their sum nearly (or completely) vanishes at an exciton state which is nearly (or completely) optically forbidden therein. EET to (or fr...

Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.

Abstract: Summary Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients

Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ.

Abstract: Escherichia coli osmosensor EnvZ is a protein histidine kinase that plays a central role in osmoregulation, a cellular adaptation process involving the His-Asp phosphorelay signal transduction system. Dimerization of the transmembrane protein is essential for its autophosphorylation and phosphorelay signal transduction functions. Here we present the NMR-derived structure of the homodimeric core domain (residues 223–289) of EnvZ that includes His 243, the site of autophosphorylation and phosphate transfer reactions. The structure comprises a four-helix bundle formed by two identical helix-turn-helix subunits, revealing the molecular assembly of two active sites within the dimeric kinase.

Gender-related differences in pharmacokinetics and their clinical significance.

Abstract: In this review I have attempted to summarize gender differences in pharmacokinetics involving the cytochrome P450 (CYP) isozymes of young and mature adults, excluding the effects of the menstrual cycle, use of oral contraceptives and pregnancy. Sex differences in drug metabolism and elimination are mainly related to steroid hormone levels. CYP3A4, responsible for the metabolism of over 50% of therapeutic drugs, exhibits higher activity in women than in men. Nonetheless, the absence of a sex difference has been reported by some workers. The activity of several other CYP (CYP2C19, CYP2D6, CYP2E1) isozymes and the conjugation (glucuronidation) activity involved in drug metabolism may be higher in men than in women. Drug metabolism in women is affected by sex-specific factors (menopause, pregnancy and menstruation) in addition to the cigarette smoking, drug ingestion and alcohol consumption that are more commonly observed factors in men. Furthermore, they are affected by physiological factors such as drug absorption, protein binding and elimination. Thus, careful attention should be paid to the side-effects and toxicity arising from sex differences in drug metabolism in clinical situations. Although there are specific ethical considerations regarding carrying out drug trials in women, the relationship between the side-effects and toxicity that may be influenced by hormones during drug metabolism and drug treatment needs further study.

Microbial degradation of polyurethane, polyester polyurethanes and polyether polyurethanes.

Abstract: Polyurethane (PUR) is a polymer derived from the condensation of polyisocyanate and polyol and it is widely used as a base material in various industries. PUR, in particular, polyester PUR, is known to be vulnerable to microbial attack. Recently, environmental pollution by plastic wastes has become a serious issue and polyester PUR had attracted attention because of its biodegradability. There are many reports on the degradation of polyester PUR by microorganisms, especially by fungi. Microbial degradation of polyester PUR is thought to be mainly due to the hydrolysis of ester bonds by esterases. Recently, polyester-PUR-degrading enzymes have been purified and their characteristics reported. Among them, a solid-polyester-PUR-degrading enzyme (PUR esterase) derived from Comamonas acidovorans TB-35 had unique characteristics. This enzyme has a hydrophobic PUR-surface-binding domain and a catalytic domain, and the surface-binding domain was considered as being essential for PUR degradation. This hydrophobic surface-binding domain is also observed in other solid-polyester-degrading enzymes such as poly(hydroxyalkanoate) (PHA) depolymerases. There was no significant homology between the amino acid sequence of PUR esterase and that of PHA depolymerases, except in the hydrophobic surface-binding region. Thus, PUR esterase and PHA depolymerase are probably different in terms of their evolutionary origin and it is possible that PUR esterases come to be classified as a new solid-polyester-degrading enzyme family.

Decay estimates of solutions for the equations of motion of compressible viscous and heat-conductive gases in an exterior domain in ℝ3

Abstract: We consider the equations of motion of compressible viscous and heat-conductive gases in an exterior domain in ℝ3. We give the L_q−L_p estimates for solutions to the linearized equations and show an optimal decay estimate for solutions to the nonlinear problem.