Showing papers by "Nagoya University published in 2002"
TL;DR: Asymmetric catalysis, in its infancy in the 1960s, has dramatically changed the procedures of chemical synthesis, and resulted in an impressive progression to a level that technically approximates or sometimes even exceeds that of natural biological processes as discussed by the authors.
Abstract: Asymmetric catalysis, in its infancy in the 1960s, has dramatically changed the procedures of chemical synthesis, and resulted in an impressive progression to a level that technically approximates or sometimes even exceeds that of natural biological processes. The recent exceptional advances in this area attest to a range of conceptual breakthroughs in chemical sciences in general, and to the practical benefits of organic synthesis, not only in laboratories but also in industry. The growth of this core technology has given rise to enormous economic potential in the manufacture of pharmaceuticals, animal health products, agrochemicals, fungicides, pheromones, flavors, and fragrances. Practical asymmetric catalysis is of growing importance to a sustainable modern society, in which environmental protection is of increasing concern. This subject is an essential component of molecular science and technology in the 21st century. Most importantly, recent progress has spurred various interdisciplinary research efforts directed toward the creation of molecularly engineered novel functions. The origin and progress of my research in this field are discussed.
1,607 citations
TL;DR: This work identifies the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate–anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricOSuric agents (which affect excretion of uric acid).
Abstract: Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.
1,274 citations
TL;DR: Rec recombinant breakpoint analysis is used to restrict the sex-determining region in medaka fish to a 530-kilobase stretch of the Y chromosome, and it is suggested that thesex-specific DMY is required for testicular development and is a prime candidate for the medaka sex-Determining gene.
Abstract: Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. Here, we used recombinant breakpoint analysis to restrict the sex-determining region in medaka fish (Oryzias latipes) to a 530-kilobase (kb) stretch of the Y chromosome. Deletion analysis of the Y chromosome of a congenic XY female further shortened the region to 250 kb. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only the DM-related PG17 was Y specific; we thus named it DMY. Two naturally occurring mutations establish DMY's critical role in male development. The first heritable mutant--a single insertion in exon 3 and the subsequent truncation of DMY--resulted in all XY female offspring. Similarly, the second XY mutant female showed reduced DMY expression with a high proportion of XY female offspring. During normal development, DMY is expressed only in somatic cells of XY gonads. These findings strongly suggest that the sex-specific DMY is required for testicular development and is a prime candidate for the medaka sex-determining gene.
1,253 citations
Harvard University1, University of Missouri2, University of British Columbia3, Heriot-Watt University4, Indiana University5, Salk Institute for Biological Studies6, Leibniz Association7, Boyce Thompson Institute for Plant Research8, Nagoya University9, University of Copenhagen10, University of Tsukuba11
TL;DR: A simplified nomenclature for Arabidopsis MAPKs and MAPK kinases is proposed that might also serve as a basis for standard annotation of these gene families in all plants.
1,072 citations
TL;DR: The chronic food shortage that was feared after the rapid expansion of the world population in the 1960s was averted largely by the development of a high-yielding semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'; this gene is identified as encoding an oxidase enzyme involved in the biosynthesis of gibberellin, a plant growth hormone.
Abstract: The chronic food shortage that was feared after the rapid expansion of the world population in the 1960s was averted largely by the development of a high-yielding semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'. The short stature of IR8 is due to a mutation in the plant's sd1 gene, and here we identify this gene as encoding an oxidase enzyme involved in the biosynthesis of gibberellin, a plant growth hormone. Gibberellin is also implicated in green-revolution varieties of wheat, but the reduced height of those crops is conferred by defects in the hormone's signalling pathway.
1,030 citations
TL;DR: It is proposed that various transmembrane proteins anchored to the actin-based membrane skeleton meshwork act as rows of pickets that temporarily confine phospholipids.
Abstract: The diffusion rate of lipids in the cell membrane is reduced by a factor of 5-100 from that in artificial bilayers. This slowing mechanism has puzzled cell biologists for the last 25 yr. Here we address this issue by studying the movement of unsaturated phospholipids in rat kidney fibroblasts at the single molecule level at the temporal resolution of 25 micros. The cell membrane was found to be compartmentalized: phospholipids are confined within 230-nm-diameter (phi) compartments for 11 ms on average before hopping to adjacent compartments. These 230-nm compartments exist within greater 750-nm-phi compartments where these phospholipids are confined for 0.33 s on average. The diffusion rate within 230-nm compartments is 5.4 microm2/s, which is nearly as fast as that in large unilamellar vesicles, indicating that the diffusion in the cell membrane is reduced not because diffusion per se is slow, but because the cell membrane is compartmentalized with regard to lateral diffusion of phospholipids. Such compartmentalization depends on the actin-based membrane skeleton, but not on the extracellular matrix, extracellular domains of membrane proteins, or cholesterol-enriched rafts. We propose that various transmembrane proteins anchored to the actin-based membrane skeleton meshwork act as rows of pickets that temporarily confine phospholipids.
910 citations
TL;DR: The data suggest that HNE mediates Aβ‐induced oxidative damage to neuronal membrane proteins, which, in turn, leads to disruption of ion homeostasis and cell degeneration.
Abstract: Peroxidation of membrane lipids results in release of the aldehyde 4-hydroxynonenal (HNE), which is known to conjugate to specific amino acids of proteins and may alter their function. Because accumulating data indicate that free radicals mediate injury and death of neurons in Alzheimer's disease (AD) and because amyloid beta-peptide (A beta) can promote free radical production, we tested the hypothesis that HNE mediates A beta 25-35-induced disruption of neuronal ion homeostasis and cell death. A beta induced large increases in levels of free and protein-bound HNE in cultured hippocampal cells. HNE was neurotoxic in a time- and concentration-dependent manner, and this toxicity was specific in that other aldehydic lipid peroxidation products were not neurotoxic. HNE impaired Na+, K(+)-ATPase activity and induced an increase of neuronal intracellular free Ca2+ concentration. HNE increased neuronal vulnerability to glutamate toxicity, and HNE toxicity was partially attenuated by NMDA receptor antagonists, suggesting an excitotoxic component to HNE neurotoxicity. Glutathione, which was previously shown to play a key role in HNE metabolism in nonneuronal cells, attenuated the neurotoxicities of both A beta and HNE. The antioxidant propyl gallate protected neurons against A beta toxicity but was less effective in protecting against HNE toxicity. Collectively, the data suggest that HNE mediates A beta-induced oxidative damage to neuronal membrane proteins, which, in turn, leads to disruption of ion homeostasis and cell degeneration.
784 citations
TL;DR: A molecular dynamics trajectory is presented that captures the molecular processes involved in the freezing of pure water and finds that ice nucleation occurs once a sufficient number of relatively long-lived hydrogen bonds develop spontaneously at the same location to form a fairly compact initial nucleus.
Abstract: Upon cooling, water freezes to ice. This familiar phase transition occurs widely in nature, yet unlike the freezing of simple liquids, it has never been successfully simulated on a computer. The difficulty lies with the fact that hydrogen bonding between individual water molecules yields a disordered three-dimensional hydrogen-bond network whose rugged and complex global potential energy surface permits a large number of possible network configurations. As a result, it is very challenging to reproduce the freezing of 'real' water into a solid with a unique crystalline structure. For systems with a limited number of possible disordered hydrogen-bond network structures, such as confined water, it is relatively easy to locate a pathway from a liquid state to a crystalline structure. For pure and spatially unconfined water, however, molecular dynamics simulations of freezing are severely hampered by the large number of possible network configurations that exist. Here we present a molecular dynamics trajectory that captures the molecular processes involved in the freezing of pure water. We find that ice nucleation occurs once a sufficient number of relatively long-lived hydrogen bonds develop spontaneously at the same location to form a fairly compact initial nucleus. The initial nucleus then slowly changes shape and size until it reaches a stage that allows rapid expansion, resulting in crystallization of the entire system.
779 citations
TL;DR: RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense, suggesting that this MAP kinases signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species.
Abstract: A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense. These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species.
761 citations
TL;DR: The results suggest that CRMP-2 regulates axonal growth and branching as a partner of the tubulin heterodimer, in a different fashion from traditional MAPs.
Abstract: Regulated increase in the formation of microtubule arrays is thought to be important for axonal growth. Collapsin response mediator protein-2 (CRMP-2) is a mammalian homologue of UNC-33, mutations in which result in abnormal axon termination. We recently demonstrated that CRMP-2 is critical for axonal differentiation. Here, we identify two activities of CRMP-2: tubulin-heterodimer binding and the promotion of microtubule assembly. CRMP-2 bound tubulin dimers with higher affinity than it bound microtubules. Association of CRMP-2 with microtubules was enhanced by tubulin polymerization in the presence of CRMP-2. The binding property of CRMP-2 with tubulin was apparently distinct from that of Tau, which preferentially bound microtubules. In neurons, overexpression of CRMP-2 promoted axonal growth and branching. A mutant of CRMP-2, lacking the region responsible for microtubule assembly, inhibited axonal growth and branching in a dominant-negative manner. Taken together, our results suggest that CRMP-2 regulates axonal growth and branching as a partner of the tubulin heterodimer, in a different fashion from traditional MAPs.
731 citations
University of Tokyo1, Boston University2, Brookhaven National Laboratory3, University of California, Irvine4, California State University, Dominguez Hills5, George Mason University6, Gifu University7, University of Hawaii8, KEK9, Kobe University10, Kyoto University11, Los Alamos National Laboratory12, Louisiana State University13, University of Maryland, College Park14, Massachusetts Institute of Technology15, University of Minnesota16, State University of New York System17, Nagoya University18, Niigata University19, Osaka University20, Seoul National University21, Shizuoka University22, Tohoku University23, Tokai University24, Tokyo Institute of Technology25, University of Warsaw26, University of Washington27
TL;DR: In this paper, a number of different fits to solar neutrino mixing and mass square difference were performed using 1496 days of Super-Kamiokande-I's solar NE data.
TL;DR: A fluorescence- or colorimetry-based allele-specific DNA-primer–probe assay system was used to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction and 2242 unrelated Japanese controls.
Abstract: Background Although epidemiologic studies have suggested that several genetic variants increase the risk of myocardial infarction, large-scale association studies that examine many polymorphisms simultaneously are required to allow reliable prediction of the genetic risk of myocardial infarction. Methods We used a fluorescence- or colorimetry-based allele-specific DNA-primer–probe assay system to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women). Results In an initial screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects, 19 polymorphisms were selected in men and 18 in women by means of logistic-regression analysis, after adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the s...
TL;DR: The result indicates that the lipid droplet surface is a hemi-membrane or a phospholipid monolayer containing cholesterol but is compositionally different from the endoplasmic reticulum membrane or the sphingolipids/cholesterol-rich microdomain.
TL;DR: It is found that pretreating rice seedlings with low levels of H2O2 and nitric oxide free radicals causes oxidative damage to plants under various abiotic stress conditions.
TL;DR: Results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization.
TL;DR: A randomized controlled study evaluated the effect of postoperative adjuvant therapy with mitomycin C and 5‐fluorouracil versus surgery alone (control arm) on survival and disease‐free survival (DFS) for each specific disease comprising resected pancreaticobiliary carcinoma (pancreatic, gallbladder, bile duct, or ampulla of Vater carcinoma) separately.
Abstract: BACKGROUND
To the authors' knowledge, the significance of postoperative adjuvant chemotherapy in pancreaticobiliary carcinoma has not yet been clarified. A randomized controlled study evaluated the effect of postoperative adjuvant therapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) (MF arm) versus surgery alone (control arm) on survival and disease-free survival (DFS) for each specific disease comprising resected pancreaticobiliary carcinoma (pancreatic, gallbladder, bile duct, or ampulla of Vater carcinoma) separately.
METHODS
Between April 1986 and June 1992, a total of 508 patients with resected pancreatic (n = 173), bile duct (n = 139), gallbladder (n = 140), or ampulla of Vater (n = 56) carcinomas were allocated randomly to either the MF group or the control group. The MF group received MMC (6 mg/m2 intravenously [i.v.]) at the time of surgery and 5-FU (310 mg/m2 i.v.) in 2 courses of treatment for 5 consecutive days during postoperative Weeks 1 and 3, followed by 5-FU (100 mg/m2orally) daily from postoperative Week 5 until disease recurrence. All patients were followed for 5 years.
RESULTS
After ineligible patients were excluded, 158 patients with pancreatic carcinoma (81 in the MF group and 77 in the control group), 118 patients with bile duct carcinoma (58 in the MF group and 60 in the control group), 112 patients with gallbladder carcinoma (69 in the MF group and 43 in the control group), and 48 patients with carcinoma of the ampulla of Vater (24 in the MF group and 24 in the control group) were evaluated. Good compliance (> 80%) was achieved with MF treatment. The 5-year survival rate in gallbladder carcinoma patients was significantly better in the MF group (26.0%) compared with the control group (14.4%) (P = 0.0367). Similarly, the 5-year DFS rate of patients with gallbladder carcinoma was 20.3% in the MF group, which was significantly higher than the 11.6% DFS rate reported in the control group (P = 0.0210). Significant improvement in body weight compared with the control was observed only in patients with gallbladder carcinoma. There were no apparent differences in 5-year survival and 5-year DFS rates between patients with pancreatic, bile duct, or ampulla of Vater carcinomas. Multivariate analyses demonstrated a tendency for the MF group to have a lower risk of mortality (risk ratio of 0.654; P = 0.0825) and recurrence (risk ratio of 0.626; P = 0.0589). The most commonly reported adverse drug reactions were anorexia, nausea/emesis, stomatitis, and leukopenia, none of which were noted to be serious.
CONCLUSIONS
The results of the current study indicate that gallbladder carcinoma patients who undergo noncurative resections may derive some benefit from systemic chemotherapy. However, alternative modalities must be developed for patients with carcinomas of the pancreas, bile duct, or ampulla of Vater. Cancer 2002;95:1685–95. © 2002 American Cancer Society.
DOI 10.1002/cncr.10831
TL;DR: The direct observation of dioxygen molecules physisorbed in the nanochannels of a microporous copper coordination polymer by the MEM (maximum entropy method)/Rietveld method, using in situ high-resolution synchrotron x-ray powder diffraction measurements is reported.
Abstract: We report the direct observation of dioxygen molecules physisorbed in the nanochannels of a microporous copper coordination polymer by the MEM (maximum entropy method)/Rietveld method, using in situ high-resolution synchrotron x-ray powder diffraction measurements. The obtained MEM electron density revealed that van der Waals dimers of physisorbed O2 locate in the middle of nanochannels and form a one-dimensional ladder structure aligned to the host channel structure. The observed O–O stretching Raman band and magnetic susceptibilities are characteristic of the confined O2 molecules in one-dimensional nanochannels of CPL-1 (coordination polymer 1 with pillared layer structure).
TL;DR: The interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA, and the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration.
Abstract: We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.
TL;DR: The theory, uses, measurement or estimation, limitations and reliability of these parameters, which are a measure of the strength of sorption of pesticides to soils and other geosorbent surfaces at the water/solid interface, are examined.
Abstract: The soil sorption coefficient Kd and the soil organic carbon sorption coefficient KOC of pesticides are basic parameters used by environmental scientists and regulatory agencies worldwide in describing the environmental fate and behavior of pesticides. They are a measure of the strength of sorption of pesticides to soils and other geosorbent surfaces at the water/solid interface, and are thus directly related to both environmental mobility and persistence. KOC is regarded as a 'universal' parameter related to the hydrophobicity of the pesticide molecule, which applies to a given pesticide in all soils. This assumption is known to be inexact, but it is used in this way in modeling and estimating risk for pesticide leaching and runoff. In this report we examine the theory, uses, measurement or estimation, limitations and reliability of these parameters and provide some 'rules of thumb' for the use of these parameters in describing the behavior and fate of pesticides in the environment, especially in analysis by modeling.
TL;DR: F influenza-associated encephalitis/encephalopathy progressed rapidly and was associated with poor outcomes, and thrombocytopenia and severely elevated transaminase levels were factors associated with a poor prognosis.
Abstract: During the winter of 1998-1999, there was an outbreak of encephalitis/encephalopathy in Japan that appeared to be associated with influenza. We conducted a national survey of the prevalence and clinical features of disease and the associated outcomes and prognostic factors related to this outbreak. A total of 202 cases were analyzed, of which 148 were diagnosed as influenza-associated encephalitis/encephalopathy on the basis of virologic analysis. Of the 148 cases studied, 130 (87.8%) were type A influenza and 17 were type B. Encephalitis/ encephalopathy developed mainly in children age <5 years, either on the day that influenza signs appeared or on the next day. The major signs included altered consciousness or loss of consciousness, convulsions, cough, and vomiting. In many patients, multiple-organ failure developed, and rates of mortality (31.8%) and disability (27.7%) were high. Thrombocytopenia and severely elevated transaminase levels were factors associated with a poor prognosis. Thus, influenza-associated encephalitislencephalopathy progressed rapidly and was associated with poor outcomes.
TL;DR: GA signal transduction is regulated by the appearance or disappearance of the nuclear SLR1 protein, which is controlled by the upstream GA signal.
Abstract: The slender rice1 mutant (slr1) shows a constitutive gibberellin (GA) response phenotype. To investigate the mode of action of SLR1, we generated transgenic rice expressing a fusion protein consisting of SLR1 and green fluorescent protein (SLR1-GFP) and analyzed the phenotype of the transformants and the subcellular localization of GFP in vivo. SLR1-GFP worked in nuclei to repress the GA signaling pathway; its overproduction caused a dwarf phenotype. Application of GA3 to SLR1-GFP overproducers induced GA actions such as shoot elongation, downregulation of GA 20-oxidase expression, and upregulation of SLR1 expression linked with the disappearance of the nuclear SLR1-GFP protein. We also performed domain analyses of SLR1 using transgenic plants overproducing different kinds of truncated SLR1 proteins. The analyses revealed that the SLR1 protein can be divided into four parts: a GA signal perception domain located at the N terminus, a regulatory domain for its repression activity, a dimer formation domain essential for signal perception and repression activity, and a repression domain at the C terminus. We conclude that GA signal transduction is regulated by the appearance or disappearance of the nuclear SLR1 protein, which is controlled by the upstream GA signal.
TL;DR: Overall, the data demonstrate that there are raft-related domains present in certain regions of the plasma membrane of C3H cells, which can persist for tens of seconds.
Journal Article•
TL;DR: The B meson decay modes B -->Dpp; and B-->D(*)pp; have been studied using 29.4 fb(-1) of data collected with the Belle detector at KEKB using the corresponding upper limits at 90% C.L. are presented.
Abstract: The B meson decay modes B → Dpp and B → D*pp have been studied using 29.4 fb - 1 of data collected with the Belle detector at KEKB. The B 0 → D 0 pp and B 0 → D* 0 pp decays have been observed for the first time with branching fractions B(B 0 → D 0 pp) = (1.18 ′ 0.15 ′ 0.16) X 10 - 4 and B(B 0 → D* 0 pp) = (1.20 + 0 . 3 3 - 0 . 2 9 ′ 0.21) X 10 - 4 . No signal has been found for the B + → D + pp and B + → D* + pp decay modes, and the corresponding upper limits at 90% C.L. are presented.
TL;DR: The results suggest the therapeutic potential of hormonal intervention for SBMA, and nuclear translocation of the mutant AR by testosterone contributed to the phenotypic difference with gender and the effects of hormonal interventions.
TL;DR: A novel metabolic pathway is established, in which PGD(2), a major cyclooxygenase product in a variety of tissues, is converted to 15d-PGJ(2) via an albumin-independent mechanism, and is utilized in the cells during inflammation.
TL;DR: The expression of MK and PTN is increased in various human tumors, making them promising as tumor markers and as targets for tumor therapy, and from the viewpoints of the treatment of neurodegenerative diseases, increasing the efficiency of in vitro development, and the prevention of HIV infection.
Abstract: Midkine (MK) and pleiotrophin (PTN) are low molecular weight proteins with closely related structures. They are mainly composed of two domains held by disulfide bridges, and there are three antiparallel beta-sheets in each domain. MK and PTN promote the growth, survival, and migration of various cells, and play roles in neurogenesis and epithelial mesenchymal interactions during organogenesis. A chondroitin sulfate proteoglycan, protein-tyrosine phosphatase zeta (PTPzeta), is a receptor for MK and PTN. The downstream signaling system includes ERK and PI3 kinase. MK binds to the chondroitin sulfate portion of PTPzeta with high affinity. Among the various chondroitin sulfate structures, the E unit, which has 4,6-disulfated N-acetylgalactosamine, provides the strongest binding site. The expression of MK and PTN is increased in various human tumors, making them promising as tumor markers and as targets for tumor therapy. MK and PTN expression also increases upon ischemic injury. MK enhances the migration of inflammatory cells, and is involved in neointima formation and renal injury following ischemia. MK is also interesting from the viewpoints of the treatment of neurodegenerative diseases, increasing the efficiency of in vitro development, and the prevention of HIV infection.
TL;DR: A method for dividing a semiconductor nanotube into multiple quantum dots with lengths of about 10 nm by inserting Gd@C82 endohedral fullerenes is reported, which could be used for nano-electronics and nano-optoelectronics.
Abstract: Motivated by the technical and economic difficulties in further miniaturizing silicon-based transistors with the present fabrication technologies, there is a strong effort to develop alternative electronic devices, based, for example, on single molecules. Recently, carbon nanotubes have been successfully used for nanometre-sized devices such as diodes, transistors, and random access memory cells. Such nanotube devices are usually very long compared to silicon-based transistors. Here we report a method for dividing a semiconductor nanotube into multiple quantum dots with lengths of about 10nm by inserting Gd@C82 endohedral fullerenes. The spatial modulation of the nanotube electronic bandgap is observed with a low-temperature scanning tunnelling microscope. We find that a bandgap of approximately 0.5eV is narrowed down to approximately 0.1eV at sites where endohedral metallofullerenes are inserted. This change in bandgap can be explained by local elastic strain and charge transfer at metallofullerene sites. This technique for fabricating an array of quantum dots could be used for nano-electronics and nano-optoelectronics.
TL;DR: It is demonstrated that Rho/ROCK pathway negatively regulates eNOS phosphorylation through inhibition of PKB, whereas it downregulates eNos expression independent of P KB.
Abstract: Endothelial nitric oxide synthase (eNOS) is an important regulator of cardiovascular homeostasis by production of nitric oxide (NO) from vascular endothelial cells. It can be activated by protein kinase B (PKB)/Akt via phosphorylation at Ser-1177. We are interested in the role of Rho GTPase/Rho kinase (ROCK) pathway in regulation of eNOS expression and activation. Using adenovirus-mediated gene transfer in human umbilical vein endothelial cells (HUVECs), we show here that both active RhoA and ROCK not only downregulate eNOS gene expression as reported previously but also inhibit eNOS phosphorylation at Ser-1177 and cellular NO production with concomitant suppression of PKB activation. Moreover, coexpression of a constitutive active form of PKB restores the phosphorylation but not gene expression of eNOS in the presence of active RhoA. Furthermore, we show that thrombin inhibits eNOS phosphorylation, as well as expression via Rho/ROCK pathway. Expression of the active PKB reverses eNOS phosphorylation but has no effect on downregulation of eNOS expression induced by thrombin. Taken together, these data demonstrate that Rho/ROCK pathway negatively regulates eNOS phosphorylation through inhibition of PKB, whereas it downregulates eNOS expression independent of PKB.