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461.
Tadashi Shimizu Mitsuto Iwanaga Akio Yasunaga Yoshishige Urata Shinji Goto Shobu Shibata Takahito Kondo 《Cellular and molecular neurobiology》1998,18(3):299-310
1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, whereas oxidative stress by the radiation can cause cellular responses to defense cellular injury. In this study, the metabolism of antioxidants in response to ionizing radiation to the brain was studied in the brain using experimental rabbits.2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activity of a GSH synthesizing enzyme, -glutamylcysteine synthetase (-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes were dependent on the radiation dose.3. Previous intrathecal-administration of buthionine sulfoximine (100 M), a specific inhibitor of -GCS, increased DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation.4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to ionizing radiation and this induction of antioxidants may play a role in reducing tissue damage in radiotherapy. 相似文献
462.
Evolutionary relationships of human populations on a global scale 总被引:28,自引:2,他引:26
Using gene frequency data for 29 polymorphic loci (121 alleles), we
conducted a phylogenetic analysis of 26 representative populations from
around the world by using the neighbor-joining (NJ) method. We also
conducted a separate analysis of 15 populations by using data for 33
polymorphic loci. These analyses have shown that the first major split of
the phylogenetic tree separates Africans from non-Africans and that this
split occurs with a 100% bootstrap probability. The second split separates
Caucasian populations from all other non-African populations, and this
split is also supported by bootstrap tests. The third major split occurs
between Native American populations and the Greater Asians that include
East Asians (mongoloids), Pacific Islanders, and Australopapuans (native
Australians and Papua New Guineans), but Australopapuans are genetically
quite different from the rest of the Greater Asians. The second and third
levels of population splitting are quite different from those of the
phylogenetic tree obtained by Cavalli- Sforza et al. (1988), where
Caucasians, Northeast Asians, and Ameridians from the Northeurasian
supercluster and the rest of non- Africans form the Southeast Asian
supercluster. One of the major factors that caused the difference between
the two trees is that Cavalli-Sforza et al. used unweighted pair-group
method with arithmetic mean (UPGMA) in phylogenetic inference, whereas we
used the NJ method in which evolutionary rate is allowed to vary among
different populations. Bootstrap tests have shown that the UPGMA tree
receives poor statistical support whereas the NJ tree is well supported.
Implications that the phylogenetic tree obtained has on the current
controversy over the out-of-Africa and the multiregional theories of human
origins are discussed.
相似文献
463.
Phylogenetic test of the molecular clock and linearized trees 总被引:30,自引:7,他引:23
To estimate approximate divergence times of species or species groups with
molecular data, we have developed a method of constructing a linearized
tree under the assumption of a molecular clock. We present two tests of the
molecular clock for a given topology: two-cluster test and branch-length
test. The two-cluster test examines the hypothesis of the molecular clock
for the two lineages created by an interior node of the tree, whereas the
branch-length test examines the deviation of the branch length between the
tree root and a tip from the average length. Sequences evolving excessively
fast or slow at a high significance level may be eliminated. A linearized
tree will then be constructed for a given topology for the remaining
sequences under the assumption of rate constancy. We have used these
methods to analyze hominoid mitochondrial DNA and drosophilid Adh gene
sequences.
相似文献
464.
Using linear invariants for various models of nucleotide substitution, we
developed test statistics for examining the applicability of a specific
model to a given dataset in phylogenetic inference. The models examined are
those developed by Jukes and Cantor (1969), Kimura (1980), Tajima and Nei
(1984), Hasegawa et al. (1985), Tamura (1992), Tamura and Nei (1993), and a
new model called the eight-parameter model. The first six models are
special cases of the last model. The test statistics developed are
independent of evolutionary time and phylogeny, although the variances of
the statistics contain phylogenetic information. Therefore, these
statistics can be used before a phylogenetic tree is estimated. Our
objective is to find the simplest model that is applicable to a given
dataset, keeping in mind that a simple model usually gives an estimate of
evolutionary distance (number of nucleotide substitutions per site) with a
smaller variance than a complicated model when the simple model is correct.
We have also developed a statistical test of the homogeneity of nucleotide
frequencies of a sample of several sequences that takes into account
possible phylogenetic correlations. This test is used to examine the
stationarity in time of the base frequencies in the sample. For Hasegawa et
al.'s and the eight-parameter models, analytical formulas for estimating
evolutionary distances are presented. Application of the above tests to
several sets of real data has shown that the assumption of stationarity of
base composition is usually acceptable when the sequences studied are
closely related but otherwise it is rejected. Similarly, the simple models
of nucleotide substitution are almost always rejected when actual genes are
distantly related and/or the total number of nucleotides examined is large.
相似文献
465.
Summary Statistical properties of Goodman et al.'s (1974) method of compensating for undetected nucleotide substitutions in evolution are investigated by using computer simulation. It is found that the method tends to overcompensate when the stochastic error of the number of nucleotide substitutions is large. Furthermore, the estimate of the number of nucleotide substitutions obtained by this method has a large variance. However, in order to see whether this method gives overcompensation when applied together with the maximum parsimony method, a much larger scale of simulation seems to be necessary. 相似文献
466.
Shinji Goto Miho Kawakatsu Shin-ichi Izumi Yoshishige Urata Kan Kageyama Yoshito Ihara Takehiko Koji Takahito Kondo 《Free radical biology & medicine》2009,46(10):1392-1403
Glutathione S-transferases (GSTs) are multifunctional enzymes involved in the protection of cellular components against anti-cancer drugs or peroxidative stress. Previously we found that GST π, an isoform of the GSTs, is transported into the nucleus. In the present study, we found that GST π is present in mitochondria as well as in the cytosol and nucleus in mammalian cell lines. A construct comprising the 84 amino acid residues in the amino-terminal region of GST π and green fluorescent protein was detected in the mitochondria. The mutation of arginine to alanine at positions 12, 14, 19, 71, and 75 in full-length GST π completely abrogated the ability to distribute in the mitochondria, suggesting that arginine, a positively charged residue, is required for the mitochondrial transport of GST π. Chemicals generating reactive oxygen species, such as rotenone and antimycin A, decreased cell viability and reduced mitochondrial membrane potential. The overexpression of GST π diminished these changes. GST π-targeting siRNA abolished the protective effect of GST π on the mitochondria under oxidative stress. The findings indicate that the peptide signal is conducive to the mitochondrial localization of GST π under steady-state conditions without alternative splicing or posttranslational modifications such as proteolysis, suggesting that GST π protects mitochondria against oxidative stress. 相似文献
467.
Three-dimensional fluorescence as a tool for investigating the dynamics of dissolved organic matter in the Lake Biwa watershed 总被引:2,自引:0,他引:2
Khan M. G. Mostofa Takahito Yoshioka Eiichi Konohira Eiichiro Tanoue Kazuhide Hayakawa Mikio Takahashi 《Limnology》2005,6(2):101-115
Quantitative and qualitative characterizations of dissolved organic matter (DOM) were carried out at the watershed level in central Japan by measuring dissolved organic carbon (DOC) concentration and the three-dimensional excitation–emission matrix (3-D EEM). DOC concentration was low (mean 37 ± 19 µM C) in the upstream waters, whereas, in general, it increased toward the downstream areas (mean 92 ± 47 µM C). Significant variations in DOC concentration were detected among rivers and channels. DOC concentration in the epilimnion of Lake Biwa increased during the summer period and decreased during the winter period. The lake hypolimnion has lower DOC concentration (mean 87 ± 7 µM C) compared with the epilimnion (107 ± 15 µM C). Fulvic acid (FA)-like substances in the DOM were directly characterized by 3-D EEM. The fluorescence peak for upstream DOM was found in regions with longer wavelengths (excitation/emission 386 ± 6/476 ± 5 nm) compared with downstream and lake DOM (351 ± 12/446 ± 15 nm and 341 ± 6/434 ± 6 nm, respectively). The DOC concentration is correlated with fluorescence peak intensity of FA-like substances in DOM in river waters. Such a relationship was not found in lake DOM. A blueshift of the fluorescence peak from upstream to lake DOM was observed. A decrease in fluorescence intensities was also detected during the summer period. These results may suggest that the degradation of FA-like substances in DOM occurs from natural solar irradiation. Protein-like fluorescence was significantly detected in the lake epilimnion during the summer period. A linear relationship between DOC concentration and protein-like fluorescence indicated that an autochthonous input of DOM gave rise to the increase in DOC concentration in the lake epilimnion during the summer. These results may suggest that the 3-D EEM can be used as a tool for the investigation of DOM dynamics at the watershed level with concurrent measurement of DOC concentration and the fluorescence properties of fulvic acid-like and protein-like substances. 相似文献
468.
MEGA2: molecular evolutionary genetics analysis software. 总被引:201,自引:0,他引:201
We have developed a new software package, Molecular Evolutionary Genetics Analysis version 2 (MEGA2), for exploring and analyzing aligned DNA or protein sequences from an evolutionary perspective. MEGA2 vastly extends the capabilities of MEGA version 1 by: (1) facilitating analyses of large datasets; (2) enabling creation and analyses of groups of sequences; (3) enabling specification of domains and genes; (4) expanding the repertoire of statistical methods for molecular evolutionary studies; and (5) adding new modules for visual representation of input data and output results on the Microsoft Windows platform. AVAILABILITY: http://www.megasoftware.net. CONTACT: s.kumar@asu.edu 相似文献
469.
So S Chijiwa T Ikeda N Nobuhisa I Oda-Ueda N Hattori S Ohno M 《Journal of molecular evolution》2008,66(3):298-307
A cDNA encoding a novel phospholipase A2 (PLA2) inhibitor (PLI) was isolated from a Protobothrops flavoviridis snake (Tokunoshima island, Japan) liver cDNA library. This cDNA encoded a signal peptide of 19 amino acids followed by a
mature protein of 181 amino acids. Its N-terminal amino acid sequence was completely in accord with that of a PLI, named PLI-II,
previously found in P. flavoviridis serum. PLI-II showed a high similarity in sequence to the B subtype of γPLI, denoted γPLI-B, isolated from Agkistrodon blomhoffii siniticus serum. Thus, PLI-II is P. flavoviridis serum γPLI-B. Since PLI-I, previously isolated from P. flavoviridis serum, can be assigned as γPLI-A, P. flavoviridis serum contains both A and B subtypes of γPLI. Phylogenetic analysis of γPLIs from the sera of various kinds of snakes, Elapinae,
Colubrinae, Laticaudinae, Acanthophiinae, Crotalinae, and Pythonidae, based on the amino acid sequences revealed that A and
B subtypes of γPLIs are clearly separated from each other. It was also found that phylogenetic topologies of γPLIs are in
good agreement with speciation processes of snakes. The BLAST search followed by analyses with particular Internet search
engines of proteins with Cys/loop frameworks similar to those of PLI-II and PLI-I revealed that γPLI-Bs, including PLI-II
and PLI-II-like proteins from mammalian sources, form a novel PLI-II family which possesses the common Cys/loop frameworks
in the anterior and posterior three-finger motifs in the molecules. Several lines of evidence suggest that PLI-II is evolutionarily
ancestral to PLI-I.
The nucleotide sequence reported in this paper is available from the GenBank/EMBL/DDBJ databases under accession number AB290845. 相似文献
470.
Hahismoto S Yazawa S Asao T Faried A Nishimura T Tsuboi K Nakagawa T Yamauchi T Koyama N Umehara K Saniabadi AR Kuwano H 《Glycoconjugate journal》2008,25(6):531-544
Chemically synthesized sugar-cholestanols with mono-, di-, and tri-saccharides attached to cholestanol showed strong inhibiting activity against the proliferation of colorectal and gastric cancer cells. In contrast, cholestanol without sugar moieties was totally ineffective. Furthermore, when cancer cells were exposed to GlcNAcRbetacholestanol (R=(-) or beta1-3Gal), the compound was rapidly taken up via the lipid rafts/microdomains on the cell surface. The uptake of sugar-cholestanol in mitochondria increased gradually and was followed by the release of cytochrome c from mitochondria and the activation of apoptotic signals through the mitochondrial pathway and the caspase cascade, leading to apoptotic cell death, characterized by DNA ladder formation and nuclear fragmentation. Additionally, the examination of GlcNAcRbetacholestanol in a mouse model of peritoneal dissemination showed a dramatic reduction of tumor growth (P < 0.003) and prolonged mouse survival time (P<0.0001). Based on these observations, we believe that the sugar-cholestanols described here have clinical potential as novel anticancer agents. 相似文献