Showing papers by "Nagoya University published in 1997"
TL;DR: Overexpression of ASK1 induced apoptotic cell death, andASK1 was activated in cells treated with tumor necrosis factor-α, and TNF-α-induced apoptosis was inhibited by a catalytically inactive form of AsK1.
Abstract: Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha). Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.
2,264 citations
TL;DR: P Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons, mediating graded Shh signaling in the ventral spinal cord and hindbrain.
1,022 citations
TL;DR: In this paper, the role of neuropilin-semaphorin-III/D-mediated chemorepulsive signals play a major role in guidance of PNS efferents.
666 citations
TL;DR: It is reported that Aβ impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation and suggested that this action of Aβ may contribute to decreased glucose uptake and neuronal degeneration in AD.
Abstract: A deficit in glucose uptake and a deposition of amyloid beta-peptide (A beta) each occur in vulnerable brain regions in Alzheimer's disease (AD). It is not known whether mechanistic links exist between A beta deposition and impaired glucose transport. We now report that A beta impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation. A beta impaired 3H-deoxy-glucose transport in a concentration-dependent manner and with a time course preceding neurodegeneration. The decrease in glucose transport was followed by a decrease in cellular ATP levels. Impairment of glucose transport, ATP depletion, and cell death were each prevented in cultures pretreated with antioxidants. Exposure to FeSO4, an established inducer of lipid peroxidation, also impaired glucose transport. Immunoprecipitation and Western blot analyses showed that exposure of cultures to A beta induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced a concentration-dependent impairment of glucose transport and subsequent ATP depletion. Impaired glucose transport was not caused by a decreased energy demand in the neurons, because ouabain, which inhibits Na+/K(+)-ATPase activity and thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose transport. Collectively, the data demonstrate that lipid peroxidation mediates A beta-induced impairment of glucose transport in neurons and suggest that this action of A beta may contribute to decreased glucose uptake and neuronal degeneration in AD.
555 citations
TL;DR: It is shown that mice homozygous for a targeted mutation in semaphorin III/D show severe abnormality in peripheral nerve projection, and this abnormality is seen in the trigeminal, facial, vagus, accessory, and glossopharyngeal nerves but not in the oculomotor nerve.
536 citations
TL;DR: It is demonstrated that E6 proteins can bind to the second PDZ domain of the human homologue of the Drosophila discs large tumor suppressor protein (hDLG) through their C-terminal XS/TXV/L motif, similar to the interaction between the adenomatous polyposis coli gene product and hDLG.
Abstract: In the majority of cervical cancers, DNAs of high-risk mucosotpropic human papillomaviruses (HPVs), such as type 16, are maintained so as to express two viral proteins, E6 and E7, suggesting an essential importance to carcinogenesis. The high-risk HPV E6 proteins are known to inactivate p53 tumor suppressor protein but appear to have an additional, molecularly unknown function(s). In this study, we demonstrate that these E6 proteins can bind to the second PDZ domain of the human homologue of the Drosophila discs large tumor suppressor protein (hDLG) through their C-terminal XS/TXV/L (where X represents any amino acid, S/T serine or threonine, and V/L valine or leucine) motif. This finding is similar to the interaction between the adenomatous polyposis coli gene product and hDLG. E6 mutants losing the ability to bind to hDLG are no longer able to induce E6-dependent transformation of rodent cells. These results suggest an intriguing possibility that interaction between the E6 protein and hDLG or other PDZ domain-containing proteins could be an underlying mechanism in the development of HPV-associated cancers.
494 citations
TL;DR: In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies, emphasizing that the length mutation of FLT3 at JM/TK-I domains were restricted to AMl and MDS.
Abstract: In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
468 citations
TL;DR: Results suggest that l-afadin serves as a linker of the actin cytoskeleton to the plasma membrane at cell-to-cell AJ, and is likely to be a rat counterpart of human AF-6 protein.
Abstract: A novel actin filament (F-actin)–binding protein with a molecular mass of ∼205 kD (p205), which was concentrated at cadherin-based cell-to-cell adherens junction (AJ), was isolated and characterized. p205 was purified from rat brain and its cDNA was cloned from a rat brain cDNA library. p205 was a protein of 1,829 amino acids (aa) with a calculated molecular mass of 207,667 kD. p205 had one F-actin–binding domain at 1,631–1,829 aa residues and one PDZ domain at 1,016– 1,100 aa residues, a domain known to interact with transmembrane proteins. p205 was copurified from rat brain with another protein with a molecular mass of 190 kD (p190). p190 was a protein of 1,663 aa with a calculated molecular mass of 188,971 kD. p190 was a splicing variant of p205 having one PDZ domain at 1,009–1,093 aa residues but lacking the F-actin–binding domain. Homology search analysis revealed that the aa sequence of p190 showed 90% identity over the entire sequence with the product of the AF-6 gene, which was found to be fused to the ALL-1 gene, known to be involved in acute leukemia. p190 is likely to be a rat counterpart of human AF-6 protein. p205 bound along the sides of F-actin but hardly showed the F-actin–cross-linking activity. Northern and Western blot analyses showed that p205 was ubiquitously expressed in all the rat tissues examined, whereas p190 was specifically expressed in brain. Immunofluorescence and immunoelectron microscopic studies revealed that p205 was concentrated at cadherin-based cell-to-cell AJ of various tissues. We named p205 l-afadin (a large splicing variant of AF-6 protein localized at adherens junction) and p190 s-afadin (a small splicing variant of l-afadin). These results suggest that l-afadin serves as a linker of the actin cytoskeleton to the plasma membrane at cell-to-cell AJ.
456 citations
TL;DR: In this paper, the effects of methanol extracts of 51 spices on scavenging were studied in detail, and the scavenger of Brassica nigra (brown mustard) was identified as a 3,5-dimethoxy-4-hydroxycinnamic acid methyl ester.
Abstract: The effects of methanol extracts of 51 spices on ·OH scavenging were studied in detail. 2-Deoxyribose oxidation and sodium benzoic acid hydroxylation methods were used for detecting the scavenging activity of ·OH. Mustard varieties, thyme, oregano, clove, and allspice all exhibited strong ·OH-scavenging activity. In particular, 3 varieties of mustard had above 90% ·OH-scavenging activity with a 1 μg/ml concentration of their extracts. The ·OH scavenger of Brassica nigra (brown mustard) was isolated and purified by XAD-2 column chromatography and preparative HPLC, and was identified as a 3,5-dimethoxy-4-hydroxycinnamic acid methyl ester by MS, ‘H-NMR, and 13C-NMR. The 3,5-dimethoxy-4-hydroxycinnamic acid methyl ester was prepared by methylating of sinapic acid with diazomethane.
442 citations
TL;DR: It is suggested that the colocalization of markers of glycoxidation (pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions in DN.
Abstract: Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function of tissue proteins and stimulates cellular responses. They have been implicated in tissue damage associated with diabetic complications. To assess the possible link between AGE accumulation and the development of diabetic nephropathy (DN), we have examined the immunohistochemical localization of various AGE structures postulated to date, i.e., pentosidine, Nepsilon-(carboxymethyl)lysine (CML), and pyrraline, in diabetic and control kidneys. CML and pentosidine accumulate in the expanded mesangial matrix and thickened glomerular capillary walls of early DN and in nodular lesions and arterial walls of advanced DN, but were absent in control kidneys. By contrast, pyrraline was not found within diabetic glomeruli but was detected in the interstitial connective tissue of both normal and diabetic kidneys. Although the distribution of pyrraline was topographically identical to type III collagen, distribution of pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization. Since oxidation is linked closely to the formation of pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of pentosidine and CML accumulation. Consistent with our assumption, diabetic nodular lesions were stained positive for MDA. These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions. Thus, glycoxidation markers may serve as useful biomarkers of oxidative damage in DN.
418 citations
TL;DR: These findings identify Ret and NTNR-α as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotrophic and differentiation factors composed of a shared transmembrane protein tyrosine kinase and a lig and-specific GPI-linked protein.
Abstract: Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent survival factors for sympathetic, sensory and central nervous system neurons. GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha. We further demonstrate that NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity; that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN, in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These findings identify Ret and NTNR-alpha as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotrophic and differentiation factors composed of a shared transmembrane protein tyrosine kinase and a ligand-specific GPI-linked protein.
TL;DR: In this paper, an optically inactive polyacetylene, poly((4-carboxyphenyl)acetylene) (poly-1), exhibits an induced circular dichroism (ICD) in the UV−visible region upon complexation with chiral amines and amino alcohols in DMSO and in the film, the sign reflecting the stereochemistry including bulkiness, type (primary, secondary, or tertiary), and absolute configuration of the amines.
Abstract: An optically inactive polyacetylene, poly((4-carboxyphenyl)acetylene) (poly-1), exhibits an induced circular dichroism (ICD) in the UV−visible region upon complexation with chiral amines and amino alcohols in DMSO and in the film, the sign of which reflects the stereochemistry including bulkiness, type (primary, secondary, or tertiary), and absolute configuration of the amines. Therefore, the polyacetylene can be used as a novel probe for determining the chirality of amines. Most primary amines and amino alcohols of the same configuration gave the same sign for the induced Cotton effect; however, secondary and/or tertiary amines used in the present study tended to show Cotton effect signs opposite to those of the primary amines and amino alcohols of the same configuration. The magnitude of the ICD likely increases with an increase in the bulkiness of the chiral amines. The complexation dynamics during the formation of the helical structure of poly-1 with chiral amines were investigated on the basis of the...
TL;DR: The recently determined entire genomic sequence of Escherichia coli allowed us to compile systematically a complete list of genes encoding such two- component signal transduction proteins, and revealed that at least 62 open reading frames (ORFs) were identified as putative members of the two-component signal transducers in this single species.
Abstract: Bacteria have devised sophisticated His-Asp phosphorelay signaling systems for eliciting a variety of adaptive responses to their environment, which are generally referred to as the "two-component regulatory system." The widespread occurrence of the His-Asp phosphorelay signaling in both prokaryotes and eukaryotes implies that it is a powerful device for a wide variety of adaptive responses of cells to their environment. The two-component signal transducers contain one or more of three common and characteristic phosphotransfer signaling domains, named the "transmitter, receiver, and histidine-containing phosphotransfer (HPt) domains." The recently determined entire genomic sequence of Escherichia coli allowed us to compile systematically a complete list of genes encoding such two-component signal transduction proteins. The results of such an effort, made in this study, revealed that at least 62 open reading frames (ORFs) were identified as putative members of the two-component signal transducers in this single species. Among them, 32 were identified as response regulator and 23 were identified as orthodox sensory kinases. In addition, E. coli has five hybrid sensory kinases. The precise location of each ORF was mapped on a physical map of the entire E. coli genome. All of these ORFs were then compiled and annotated extensively.
TL;DR: Evidence is provided that 4-hydroxynonenal, an aldehydic product of lipid peroxidation, mediates oxidation-induced impairment of glutamate transport and mitochondrial function in synapses and plays important roles in oxidative impairment of synaptic functions that would be expected to promote excitotoxic cascades.
TL;DR: Results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation, and suggest that the ceramide/SAPK/ JNK signaling pathway is required for stress-induced apoptosis.
TL;DR: Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts, and high ldh level, and low fibrinogen concentration, suggesting that FLT 3/ ITD plays a significant role in progression of APL.
Abstract: FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.
TL;DR: Electroporation would provide a useful and efficient nonviral means of foreign gene transfection to somatic cells of living chicken embryos in ovo and suggest that as far as transient gene expression is concerned is concerned.
TL;DR: An anomalous negative temperature dependence of electrical resistivity has been observed in alloys with V compositions up to $x\phantom{\rule{0ex}{0ex}}= \phantom {0ex} 0.35} as discussed by the authors.
Abstract: An anomalous negative temperature dependence of electrical resistivity has been observed in $({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{V}}_{x}{)}_{3}\mathrm{Al}$ alloys with V compositions up to $x\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.35$. In particular, the Heusler-type ${\mathrm{Fe}}_{2}\mathrm{VAl}$ compound is found to be on the verge of magnetic ordering and to exhibit a semiconductorlike behavior with the resistivity reaching $3000\ensuremath{\mu}\ensuremath{\Omega}\mathrm{cm}$ at 2 K, in spite of the possession of a clear Fermi cutoff as revealed in photoemission valence-band spectra. A substantial mass enhancement deduced from specific heat measurements suggests that ${\mathrm{Fe}}_{2}\mathrm{VAl}$ is a possible candidate for a $3d$ heavy-fermion system.
TL;DR: A nationwide epidemiological survey was conducted in 1995 to estimate an annual number of patients treated for Moyamoya disease in Japan and to describe the clinico-epidemiological features, and the present findings were quite comparable with those obtained in the previous nationwide Epidemiological survey in 1990.
TL;DR: Three mechanisms have been proposed to explain this hypothyroid-like action of amiodarone, which may cause antiarrhythmic remodeling of cardiac cells, probably through a modulation of gene expression of ion channels and other functional proteins.
Abstract: The complex profile of amiodarone actions on the electrophysiological properties of cardiac cells reviewed in this article may be summarized as follows. As acute effects, amiodarone inhibits both inward and outward currents. The inhibition of inward Na+ and Ca2+ currents is enhanced in a use- and voltage-dependent manner, resulting in suppression of excitability and conductivity in both iNa- and iCa-dependent cardiac tissues. The inhibition is greater in the tissues stimulated at higher frequencies, and in those with less negative resting (or diastolic) membrane potentials. As outward currents, iK (iKr and iKs), iK,ACh and iK,Na are inhibited by acute amiodarone, iKl could also be inhibited at high concentrations of amiodarone. Acute effects of amiodarone on i(to) remain unclear. Previous reports on the acute effects of amiodarone on APD are conflicting, presumably because different ionic currents are responsible for the repolarization of action potential in different animal species, cardiac tissues and experimental conditions. APD would be shortened if the inhibitory action of amiodarone on the inward current is greater than on the outward current, and vice versa in the opposite case. The major and consistent chronic effect of amiodarone is a moderate APD prolongation with minimal frequency-dependence. This prolongation is most likely due to a decrease in the current density of iK and i(to). Chronic effects of amiodarone are modulated by tissue accumulation of amiodarone and DEA. Variable suppression of excitability and conductivity of the heart by chronic amiodarone might reflect direct acute effects of the parent drug and/or its active metabolite (DEA) retained at the sites of action. Chronic amiodarone was shown to cause a down-regulation of Kv1.5 mRNA in rat hearts, suggesting a drug-induced modulation of potassium channel gene expression. Electrophysiological changes in the heart induced by chronic amiodarone resemble those induced by hypothyroidism. Three mechanisms have been proposed to explain this hypothyroid-like action of amiodarone. Amiodarone and/or DEA may inhibit peripheral conversion from T4 to T3, cellular uptake of T4 and T3, and T3 binding to nuclear receptors (TR). The second and third mechanisms are considered to be more important than the first. Amiodarone or DEA could antagonize T3 action on the heart at a cellular or subcellular level. Two distinct characteristics in the cellular electropharmacology or amiodarone are different from those of other antiarrhythmic drugs. First, it acts on many different types of molecular targets including Na+, Ca2+, and K+ channels as well as adrenoceptors. Second, it may cause antiarrhythmic remodeling of cardiac cells, probably through a modulation of gene expression of ion channels and other functional proteins. We hypothesize that this remodeling is mediated most likely by cellular or subcellular T3 antagonism. Nevertheless, much remains to be studied as ot the acute and especially chronic effects of amiodarone on ionic currents, transporters, receptors and other molecules in cardia cells. The role of the cardiac hypothyroid state in the genesis of antiarrhythmic activity is still a matter of considerable controversy among investigators. Recently, two amiodarone analogues (SR 33589 and ATI-2001) showing a potent acute antiarrhythmic activity in animal models, have been developed [37,87,88,131]. These new compounds are not known to exhibit chronic antiarrhythmic potential or cardiac hypothyroidism activity. Unraveling these tissues will be required to understand the exact molecular and cellular mode of action of amiodarone and to find a new direction for the development of the ideal antiarrhythmic drugs of the future.
TL;DR: The authors compared pairs of subjects with single subjects in a task of discovering scientific laws with the aid of experiments and found that pairs were more successful in discovery than Singles and participated more actively in explanatory activities (i.e., entertaining hypotheses and considering alternative ideas and justifications).
TL;DR: The somatically acquired mutations and oxidative damage of the genome, which lead an individual to the fragmentation of mitochondrial DNA, cellular energy crisis, naturally occurring cell death (apoptosis), and tissue degeneration and atrophy, are reviewed.
Abstract: This review is devoted to the molecular genetics and bioenergetics of human mitochondria related to the mechanism of aging. Morphological and functional changes of mitochondria associated with age and age-related disease are overviewed with special reference to the changes in enzymes encoded by mitochondrial-inherent genome. The somatically acquired mutations and oxidative damage of the genome, which lead an individual to the fragmentation of mitochondrial DNA, cellular energy crisis, naturally occurring cell death (apoptosis), and tissue degeneration and atrophy, are reviewed with relation to the inherited point mutational genotypes and the deletion types of mitochondrial DNA. Theories of aging are discussed with disclosed evidence relevant to them. Some trials to prevent age-related damage in mitochondria are introduced for the development of what may be called mitochondrial medicine.
TL;DR: The complete nucleotide sequence of the chloroplast genome from the unicellular green alga Chlorella vulgaris C-27 has been determined and the existence of two adjacent genes homologous to bacterial genes involved in cell division, minD and minE, suggests that C. vulgaris is closer to land plants than to red and brown algae.
Abstract: The complete nucleotide sequence of the chloroplast genome (150,613 bp) from the unicellular green alga Chlorella vulgaris C-27 has been determined. The genome contains no large inverted repeat and has one copy of rRNA gene cluster consisting of 16S, 23S, and 5S rRNA genes. It contains 31 tRNA genes, of which the tRNALeu(GAG) gene has not been found in land plant chloroplast DNAs analyzed so far. Sixty-nine protein genes and eight ORFs conserved with those found in land plant chloroplasts have also been found. The most striking is the existence of two adjacent genes homologous to bacterial genes involved in cell division, minD and minE, which are arranged in the same order in Escherichia coli. This finding suggests that the mechanism of chloroplast division is similar to bacterial division. Other than minD and minE homologues, genes encoding ribosomal proteins L5, L12, L19, and S9 (rpl5, rpl12, rpl19, and rps9); a chlorophyll biosynthesis Mg chelating subunit (chlI); and elongation factor EF-Tu (tufA), which have not been reported from land plant chloroplast DNAs, are present in this genome. However, many of the new chloroplast genes recently found in red and brown algae have not been found in C. vulgaris. Furthermore, this algal species possesses two long ORFs related to ycf1 and ycf2 that are exclusively found in land plants. These observations suggest that C. vulgaris is closer to land plants than to red and brown algae.
TL;DR: In this paper, the constitutive and evolution equations of elastic-brittle damage materials are developed on the basis of irreversible thermodynamic theory for constitutive equations, and a damage dissipation potential related to the entropy production rate is expressed in terms of damage conjugate force.
TL;DR: Ratios of urinary 8‐hydroxy‐2′‐deoxyguanosine to urinary creatinine (8‐OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation and found an increase in non‐small‐cell carcinoma patients during the course of radiotherapy and chemotherapy.
TL;DR: Multivariate analysis incorporating prognostic factors from the international prognostic index demonstrated that p53 mutations had independent effects on the rates of complete remission and survival.
Abstract: Background Mutations of the p53 gene are associated with a poor prognosis in several types of cancer. We investigated the prognostic importance of p53 mutations in patients with aggressive B-cell lymphoma. Methods We examined the relation between the presence or absence of a detectable p53 mutation in lymphoma cells and the response to chemotherapy and overall survival in 102 previously untreated patients with aggressive B-cell lymphoma. Mutations of the p53 gene were identified by polymerase-chain-reaction–mediated analysis of single-strand conformation polymorphisms and by direct sequencing. Results Of 102 cases of aggressive B-cell lymphoma, 22 (22 percent) involved p53 mutations. The rate of complete remission was significantly lower in patients with a tumor carrying a p53 mutation (6 of 22 patients, 27 percent) than in those with the wild-type p53 gene (61 of 80 patients, 76 percent) (P<0.001). Overall survival was significantly lower among patients with p53 mutations than among those with the wild-t...
TL;DR: It is demonstrated that the cardiomyopathy in the BIO14.6 hamster results from a mutation in the delta-sarcoglycan gene that maps to the disease locus, the first animal model identified for human sarcoglycan disorders.
Abstract: The BIO14.6 hamster is a widely used model for autosomal recessive cardiomyopathy. These animals die prematurely from progressive myocardial necrosis and heart failure. The primary genetic defect leading to the cardiomyopathy is still unknown. Recently, a genetic linkage map localized the cardiomyopathy locus on hamster chromosome 9qa2.1-b1, excluding several candidate genes. We now demonstrate that the cardiomyopathy results from a mutation in the delta-sarcoglycan gene that maps to the disease locus. This mutation was completely coincident with the disease in backcross and F2 pedigrees. This constitutes the first animal model identified for human sarcoglycan disorders.
TL;DR: The generation and characterization of mice lacking the nociceptin receptor and insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice indicate that the nOCiceptin system is not essential for regulation of nocICEption or locomotor activity.
Abstract: In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.
TL;DR: Results suggest that hypermethylation of the p15INK4B gene is involved in the pathogenesis of M DS and is one of the important late events during the development of MDS.