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N Takahata

Publications and source records attributed to N Takahata.

At least 19 recordsLinked to original sources
PubMed2000

The origin and age of haplochromine fishes in Lake Victoria, east Africa.

According to a widely held view, the more than 300 species of haplochromine cichlid fishes in Lake Victoria (LV), East Africa, originated from a single founder species in less than 12,000 years. This view, however, does not follow from the published geological and molecular evidence. The former does indeed suggest that the LV basin dried out less than 15,000 years ago, but it does not provide any information about the species that re-colonized the new lake or that remained in the rivers draining the area. The molecular evidence is inconclusive with respect to the origin of the LV haplochromines because cichlids from critical regions around LV were not adequately sampled; and as far as the age of the LV haplochromines is concerned, it in fact led to an estimate of 250,000-750,000 years old. In the present study, mitochondrial DNA (control region) variation was determined by heteroduplex and sequencing analyses of more than 670 specimens collected at widely distributed East African riverine and lacustrine localities. The analyses revealed the existence of seven haplogroups (I-VII) distinguishable by characteristic substitutions. All endemic LV samples tested fell into one of these haplogroups (V) which, however, was also found to be present at various other localities, both riverine and lacustrine, outside LV. Within this haplogroup, four subgroups (VA through VD) could be distinguished, two of which (VB and VC) were represented in LV and at other localities. The great majority of the LV haplochromine species could be classified as belonging to the VC subgroup, which was found only in LV and in the rivers draining into it. Hence, while the endemic haplochromine species of LV could not have originated from a single founding population, the lake does harbour a large species flock which probably arose in situ.

Africa, Eastern↗
PubMed2000

DNA archives and our nearest relative: the trichotomy problem revisited.

Ever since Thomas H. Huxley correctly identified the chimpanzee and the gorilla as the two closest relatives of the human, the problem of the relationship among the three species ("the trichotomy problem") has remained unresolved. Comparative morphology and other classical methods of biological investigation have failed to answer definitively whether the chimpanzee or the gorilla is the closest relative of the human species. DNA sequences, both mitochondrial and nuclear, too, have provided equivocal solutions, depending on the region of the genome analyzed. Random sorting of ancestral allelic lineages, sequence convergence, and sequence exchanges between alleles or duplicated loci have been identified as likely factors confounding the interpretation of the interrelationships among the three species. In the present study most of these difficulties are overcome by identifying evolutionary causes that might potentially provide misleading information. Altogether, 45 loci consisting of 46, 855 bp are analyzed. About 60% of the loci and approximately the same proportion of phylogenetically informative sites support the human-chimpanzee clade. The remaining 40% of loci and sites support the two alternatives equally. It is demonstrated that, while incompatibility between loci can be explained by random sorting of allelic lineages, incompatibility within loci must be attributed largely to the joint effect of recombination and genetic drift. The trichotomy problem can be properly addressed only within this framework.

Alleles↗
PubMed2000

Helium flux from a sedimentary basin.

The tritium-3He ages of groundwaters collected from the Saijo Basin in Japan were measured. The ages vary between 11.7 and 16.3 years. The 4He flux of >3 x 10(4) atoms/cm2 s is calculated by the 4He concentrations and ages. In addition the helium flux of 8.3 x 10(5) atoms/cm2 s is calculated at the Higashi-Niigata gas field in Japan. The above two estimates are consistent with the continental helium flux reported in the literature, suggesting that helium flux on the Earth's crust is uniform.

Geologic Sediments↗
PubMed1999

Evolution of Mhc-DRB introns: implications for the origin of primates.

Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions. Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian orders-Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my) of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta superorder, and to confirm the monophyly of the Chiroptera.

Animals↗
PubMed1999

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease.

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.

Adult↗
PubMed1999

Alterations of tubulin function caused by chronic antidepressant treatment in rat brain.

1. Antidepressants have been used clinically for many years; however, the neurochemical mechanism for their therapeutic effect has not been clarified yet. Recent reports indicate that chronic antidepressant treatment directly affects the postsynaptic membrane to increase the coupling between the stimulatory GTP-binding (G) protein, Gs, and adenylyl cyclase. Tubulin, a cytoskeletal element, is involved in the stimulatory and inhibitory regulation of adenylyl cyclase in rat cerebral cortex via direct transfer of GTP to G proteins. In this study, we investigated whether the functional change of the adenylyl cyclase system caused by chronic antidepressant treatment involves an alteration of tubulin function in the regulation of adenylyl cyclase activity. 2. Male Sprague-Dawley rats were treated once daily with amitriptyline or saline by intraperitoneal injection (10 mg/kg) for 21 days, and their cerebral cortex membranes and GppNHp-liganded tubulin (tubulin-GppNHp) were prepared for what. 3. GppNHp-stimulated adenylyl cyclase activity in cortex membranes from amitriptyline-treated rats was significantly higher than that in control membranes. Furthermore, tubulin-GppNHp prepared from amitriptyline-treated rats was more potent than that from control rats in the stimulation of adenylyl cyclase activity in the cortex membranes of the controls. However, there was no significant difference in manganese-stimulated adenylyl cyclase activity between control and amitriptyline-treated rats. 4. The present results suggest that chronic antidepressant treatment enhances not only the coupling between Gs and the catalytic subunit of adenylyl cyclase but also tubulin interaction with Gs in the cerebral cortex of the rat.

Adenylyl Cyclases↗
PubMed1999

Molecular clock and recombination in primate Mhc genes.

To set an accurate chronological framework to the evolution of primate class I and II genes in the major histocompatibility complex (Mhc), the rate of silent nucleotide substitutions in exons and introns is examined for various cDNA and genome sequences currently available. The rate is sensitive to the GC content and correlates negatively with increased GC biases at the third codon positions of Mhc genes. The intergenic recombination rate in the HLA region is estimated from the synonymous nucleotide differences at 37 linked loci. Any HLA subregion is recombined more or less at the ordinary rate of 1 cM per 1 Mb, although the rate may be reduced in some subregions. This information is used to discuss HLA haplotypes when they are applied to studies of human demography. The unusual polymorphism in the alpha-helix of HLA-DRB1 is also revisited in relation to intragenic recombination, but the molecular mechanism and the evolutionary cause both remain enigmatic.

Animals↗
PubMed1999

Paleo-demography of the Drosophila melanogaster subgroup: application of the maximum likelihood method.

The species divergence times and demographic histories of Drosophila melanogaster and its three sibling species, D. mauritiana, D. simulans, and D. yakuba, were investigated using a maximum likelihood (ML) method. Thirty-nine orthologous loci for these four species were retrieved from DDBJ/EMBL/GenBank database. Both autosomal and X-linked loci were used in this study. A significant degree of rate heterogeneity across loci was observed for each pair of species. Most loci have the GC content greater than 50% at the third codon position. The codon usage bias in Drosophila loci is considered to result in the high GC content and the heterogenous rates across loci. The chi-square, G, and Fisher's exact tests indicated that data sets with 11, 23, and 9 pairs of DNA sequences for the comparison of D. melanogaster with D. mauritiana, D. simulans, and D. yakuba, respectively, retain homogeneous rates across loci. We applied the ML method to these data sets to estimate the DNA sequence divergences before and after speciation of each species pair along with their standard deviations. Using 1.6 x 10(-8) as the rate of nucleotide substitutions per silent site per year, our results indicate that the D. melanogaster lineage split from D. yakuba approximately 5.1 +/- 0.8 million years ago (mya), D. mauritiana 2.7 +/- 0.4 mya, and D. simulans 2.3 +/- 0.3 mya. It implies that D. melanogaster became distinct from D. mauritiana and D. simulans at approximately the same time and from D. yakuba no earlier than 10 mya. The effective ancestral population size of D. melanogaster appears to be stable over evolutionary time. Assuming 10 generations per year for Drosophila, the effective population size in the ancestral lineage immediately prior to the time of species divergence is approximately 3 x 10(6), which is close to that estimated for the extant D. melanogaster population. The D. melanogaster did not encounter any obvious bottleneck during the past 10 million years.

Animals↗
PubMed1998

Persistence of neutral polymorphisms in Lake Victoria cichlid fish.

Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.

Actins↗
PubMed1998

The neutral theory and natural selection in the HLA region.

Based on available DNA sequence data in the HLA region of 4 Mb, we review the degree of polymorphism at 39 loci of which most are involved in the immune system. The extent of nucleotide differences per silent site differs greatly from locus to locus. It is exceptionally high at classical MHC loci, intermediate at six MHC-related pseudogenes as well as at some loci in class I and II regions, and low in the class III region. Different exons of individual MHC loci show also different degrees of silent polymorphism; high in the exons encoding for the peptide binding region (PBR) and low in the exons encoding for trans-membranes and cytoplasmic tails. The degree of polymorphism within MHC allelic lineages is not much smaller than that between allelic lineages, contrary to the expectation where intra-allelic sequence exchanges are restricted. The observation that many allelic lineages at the HLA-DRB1 locus are combinations of distinct motifs in the beta pleated sheet and alpha helix of PBR indicates that sequence exchanges occur even within exon 2. Semi-quantitative analysis is presented about the rate of sequence exchanges between selected and linked neutral regions, although more sequence information is necessary to make definite conclusions. The extraordinary MHC polymorphism is viewed from the dual function of MHC molecules that controls the acquired immune system.

Alleles↗
PubMed1998

Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain.

Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). The role PS-1 plays in the pathogenesis of Alzheimer's disease (AD) remains unclear. Using a set of antibodies raised against PS-1 synthetic peptides, polyclonal antibody to amyloid beta protein (Abeta) and end-specific antibodies against Abeta40, and Abeta42, immunohistochemical studies were performed on brain sections obtained from AD cases and controls. The PS-1 antibodies clearly stained amyloid angiopathies in AD-affected brains, but no recognizable immunoreactions were observed in any other vessels free from amyloid involvement in either AD-affected brains or controls. Abeta antibodies and the end-specific antibody against Abeta40 also decorated amyloid angiopathies, showing localization similar to that of PS-1. Western blot analyses predominantly detected protein band polypeptide species of a 50 kDa, band, presumably full-length PS-1 protein with N-terminus antisera, since these antibodies turned out to recognize a 50-kDa full-length band in cell lysate of transfected HeLa cell overexpressing PS-1. In addition, we recognized 30, 27 and 25 kDa proteins in both AD and control brain homogenate with these antibodies. In microvessel fractions extracted from brain homogenates, the 50, and 27 kDa fragments were observed in AD-affected brains but not in those of controls. C-terminus rabbit antisera reacted strongly with the 33 and 27 kDa bands, and additionally detected a small amount of full-length PS-1 protein in extracts from AD and control brains. Our present data indicate that PS-1 might be involved in the pathogenesis of amyloid angiopathy in the AD brain.

Alzheimer Disease↗
PubMed1998

Measurement of receptor-mediated functional activation of G proteins in postmortem human brain membranes.

Guanine nucleotide-binding regulatory proteins (G proteins) play a pivotal role in receptor-mediated transmembrane signal transduction, and have been implicated in modes of action of psychotropic drugs as well as in pathogenesis of psychiatric disorders. In the present investigation, functional activation of G proteins coupled with several receptors, in particular with GABAB receptors, was assessed by agonist-induced stimulation of high-affinity GTPase, an enzyme that is intrinsic to alpha subunit of G protein, in postmortem human frontal cortical membranes. High-affinity GTPase activity was stimulated by GABA as well as (+/-)-baclofen, a selective GABAB receptor agonist, with EC50 values of 60-150 and 10-40 microM, respectively, in a Mg(2+)-dependent manner. The (+/-)-baclofen-stimulated response was antagonized by the selective GABAB receptor antagonist, 2-hydroxy-saclofen, in a competitive manner with a KB value of 59 microM. Although the maximal percent increase above basal value (% Emax) for GABAB receptor-mediated high-affinity GTPase activity was varied from subject to subject, % Emax values for both agonists were highly correlated with each other, and replicable and stable in a given subject, indicating that this measure is trustworthy as an index of functional coupling between receptors and G proteins in future studies at the aim of elucidating possible alteration of receptor/G protein interaction in psychiatric disorders. The % Emax values for GABAB receptor-mediated responses were correlated inversely with brain storage duration, which should be critically considered in postmortem studies. The increases in high-affinity GTPase activity stimulated by several agonists other than GABAB receptor agonists seemed too low to quantify for making a comparison in future studies.

Aged↗
PubMed1998

Evolutionary history and mechanism of the Drosophila cecropin gene family.

Upon bacterial infection, insects secrete a set of synthesized antibacterial proteins into the hemolymph and initiate synergistic destruction of invaders. Cecropin is one such antibacterial protein which is also found in vertebrates. To study the evolutionary history and mechanism of the Cecropin gene family, we determined DNA sequences of one isogenic In(3R)C and six isofemale lines of Drosophila melanogaster as well as one line of D. simulans and of D. yakuba. The phylogenetic analysis of these sequences together with those published for D. virilis and Sarcophaga peregrina reveals frequent gene re-organization. It was also found that silent nucleotide differences within D. melanogaster are quite heterogeneous across the gene region of approximately 3 kilobases and the extent of polymorphism is unusually usually high. These data suggest that the Cecropin gene region of D. melanogaster underwent intragenic recombination as well as introgression from a closely related sibling species, D. simulans.

Animals↗
PubMed1998

Footprints of intragenic recombination at HLA loci.

To evaluate the effect of balancing selection and intragenic recombination (or gene conversion) at six individual HLA loci, synonymous nucleotide diversity in different exon groups is examined within (pi w) and between (pi b) allelic lineages that may be defined by either serological or DNA sequence differences. Both pi values are high in exons which encode for the peptide binding region (PBR) and tend to decrease in other exons. The value of pi w is significantly smaller than that of pib in any exon of any locus. However, even pi w is much greater than nucleotide diversity at non-HLA loci. These observations provide additional strong evidence for the operation of balancing selection in PBR-encoding exons and its indirect effects on polymorphism at linked neighboring regions. It appears that allelic lineages have generally evolved in isolation but the linkage relationships within and between exons are incomplete throughout the long evolutionary history. To quantify intragenic recombination and account for the large discrepancy between the HLA and non-HLA diversity, a population genetics model is analyzed with special reference to the evolution of modern humans. The analysis suggests that the recombination rate between two sites 1000 base pairs apart is about 10(-5) per generation and that the effective size of human populations (equivalent roughly to the number of breeding individuals in a randomly mating population) has dropped from 10(5) to 10(4) in most of the Quaternary. One possibility for this reduction is discussed.

Chromosome Mapping↗
PubMed1998

Polymorphism of the HLA class II loci in Siberian populations.

The populations that colonized Siberia diverged from one another in the Paleolithic and evolved in isolation until today. These populations are therefore a rich source of information about the conditions under which the initial divergence of modern humans occurred. In the present study we used the HLA system, first, to investigate the evolution of the human major histocompatibility complex (MHC) itself, and second, to reveal the relationships among Siberian populations. We determined allelic frequencies at five HLA class II loci (DRB1, DQA1, DQB1, DPA1, and DPB1) in seven Siberian populations (Ket, Evenk, Koryak, Chukchi, Nivkh, Udege, and Siberian Eskimo) by the combination of single-stranded conformational polymorphism and DNA sequencing analysis. We then used the gene frequency data to deduce the HLA class II haplotypes and their frequencies. Despite high polymorphism at four of the five loci, no new alleles could be detected. This finding is consistent with a conserved evolution of human class II MHC genes. We found a high number of HLA class II haplotypes in Siberian populations. More haplotypes have been found in Siberia than in any other population. Some of the haplotypes are shared with non-Siberian populations, but most of them are new, and some represent "forbidden" combinations of DQA1 and DQB1 alleles. We suggest that a set of "public" haplotypes was brought to Siberia with the colonizers but that most of the new haplotypes were generated in Siberia by recombination and are part of a haplotype pool that is turning over rapidly. The allelic frequencies at the DRB1 locus divide the Siberian populations into eastern and central Siberian branches; only the former shows a clear genealogical relationship to Amerinds.

Alleles↗
PubMed1998

Calcium mobilization evoked by amyloid beta-protein involves inositol 1,4,5-triphosphate production in human platelets.

We examined the effects of amyloid beta-protein (A beta) on Ca2+ mobilization in human platelets. The addition of A beta fragments 25-35 (A beta 25-35) gradually increased the cytoplasmic free Ca2+ concentration ([Ca2+]i). After the maximum response, [Ca2+]i decreased and then reached a sustained, higher level of [Ca2+]i. Similar effects were also observed with A beta 1-40, whereas 1-28 , 12-28 and 31-35 did not affect the Ca2+ response. In the absence of extracellular Ca2+, A beta 25-35 caused a transient increase in [Ca2+]i, which returned to the resting level. U73122, a phospholipase C inhibitor, completely abolished Ca2+ mobilization induced by thrombin and A beta 25-35. Furthermore, A beta enhanced the production of inositol 1,4,5-trisphosphate (IP3) in platelets. These findings suggest that Ca2+ mobilization induced by A beta 25-35 is due to phospholipase C activation and IP3 production.

Amyloid beta-Peptides↗
PubMed1998

Differential alteration of adenylyl cyclase subtypes I, II, and V/VI in postmortem human brains of heroin addicts.

In animal and culture cell experiments, the upregulation of cAMP-related signal transduction after chronic opioid administration has been hypothesized to be an adaptive change of the molecular mechanism to maintain homeostasis in intracellular signals downstream from opioid receptors. Herein, we have examined the quantitative changes of three adenylyl cyclase (AC) subtypes (I, II, and V/VI) in temporal cortex membranes from brains of heroin addicts and age-matched controls by immunoblotting. The immunoreactivity of AC-I decreased significantly (p < 0.05) in heroin addicts, compared with controls; whereas those of AC-II and AC-V/VI were not changed. The present findings indicate that differential regulation of AC subtypes occurs and that AC-I may play an important role in the signal transduction for opiate-induced tolerance and dependence mechanisms in human brain cortex.

Adenylyl Cyclases↗