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141.
Evolutionary history of the COII/tRNALys intergenic 9 base pair deletion in human mitochondrial DNAs from the Pacific 总被引:14,自引:2,他引:12
Redd AJ; Takezaki N; Sherry ST; McGarvey ST; Sofro AS; Stoneking M 《Molecular biology and evolution》1995,12(4):604-615
Length changes in human mitochondrial DNA (mtDNA) are potentially useful
markers for inferring the evolutionary history of populations. One such
length change is a nine base pair (9-bp) deletion that is located in the
intergenic region between the COII gene and the Lysine tRNA gene
(COII/tRNALys intergenic region). This deletion has been used as a genetic
marker to trace descent from peoples of East Asian origin. A geographic
cline of the deletion frequency across modern Pacific Islander populations
suggests that the deletion may be useful for tracing prehistoric Polynesian
origins and affinities. Mitochondrial DNA sequence variation within two
variable segments of the control region (CR) permits a number of inferences
regarding the evolutionary history of the 9-bp deletion that cannot be
determined from frequency data alone. We obtained CR sequences from 74
mtDNAs with the 9-bp deletion from Indonesia, coastal Papua New Guinea
(PNG), and American Samoa. Phylogenetic and pairwise distribution analysis
of these CR sequences pooled with previously published CR sequences reveals
that the deletion arose independently in Africa and Asia and suggests
possible multiple origins of the deletion in Asia. A clinal increase of the
frequency of the 9-bp deletion across the three Pacific populations is
associated with a decrease in CR sequence diversity, consistent with
founder events. Furthermore, analysis of pairwise difference distributions
indicates an expansion time of proto-Polynesians that began 5,500 yr ago
from Southeast Asia. These results are consistent with the express train
model of Polynesian origins.
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142.
143.
Relocation of a Ca2+-dependent protein kinase activity during pollen tube reorientation 总被引:9,自引:0,他引:9 下载免费PDF全文
Pollen tube reorientation is a dynamic cellular event that is crucial for successful fertilization. We have shown previously that pollen tube orientation is regulated by cytosolic free calcium ([Ca2+]c). In this paper, we studied the activity of a Ca2+-dependent protein kinase during reorientation. The kinase activity was assayed in living cells by using confocal ratio imaging of BODIPY FL bisindolylmaleimide. We found that growing pollen tubes exhibited higher protein kinase activity in the apical region, whereas nongrowing cells showed uniform distribution. Modification of growth direction by diffusion of inhibitors/activators from a micropipette showed the spatial redistribution of kinase activity to predict the new growth orientation. Localized increases in [Ca2+]c induced by photolysis of caged Ca2+ that led to reorientation also increased kinase activity. Molecular and immunological assays suggest that this kinase may show some functional homology with protein kinase C. We suggest that the tip-localized gradient of kinase activity promotes Ca2+-mediated exocytosis and may act to regulate Ca2+ channel activity. 相似文献
144.
145.
Schwaiger FW; Weyers E; Buitkamp J; Ede AJ; Crawford A; Epplen JT 《Molecular biology and evolution》1994,11(2):239-249
Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined for
polymorphisms in both the antigen-binding regions and the adjacent intronic
mixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles were
identified. Short nucleotide motifs are extensively shared between certain
exon 2 regions of Ovar-DRB alleles. The simple repeat variations, the
number of different amino acids at usually polymorphic sites, and the
number of silent substitutions were reduced in the intraspecies analyses of
sheep DRB sequences, compared with those of cattle and goats. It was
paradoxical that the abundance of different sheep alleles was similar to
that of cattle and goats. This paradox may be explained by postulating a
relatively small number of "ancient" alleles, with the present-day Ovar-DRB
alleles being generated by reciprocal exchange of nucleotide motifs. At the
antigen-binding sites, new combinations of amino acids were maintained in
Ovar-DRB alleles by strong positive selection. In sheep--and less
pronounced in goats and cattle--the DRB alleles can be divided into two
groups. In one group, silent substitutions are increased when compared with
the other. This suggests separate evolutionary pathways for certain groups
of DRB alleles within a species. The simple repetitive sequences are also
discussed with respect to the evolution of DRB alleles.
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146.
Robert A Clayton Colin AJ Dick Alison Mackenzie Michiaki Nagasawa Deirdre Galbraith Stuart F Hastings Simon J MacKenzie 《Respiratory research》2004,5(1):4
BackgroundThe anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control.MethodsControl and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days.ResultsWhen used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil.ConclusionsThese results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor. 相似文献
147.
Antony PB Black Hansha Bhayani Clive AJ Ryder Janet MM Gardner-Medwin Taunton R Southwood 《Arthritis research & therapy》2001,4(3):177
A study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferation in situ. Mononuclear cells were isolated from 44 paired samples of peripheral blood and SF. Differentiation and activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell-cycle analysis was performed by propidium iodide staining, and surface-marker expression was also assessed after culture of the T cells under conditions similar to those found in the synovial compartment. The majority of the T cells in the SF were CD45RO+CD45RBdull. There was greater expression of the activation markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from peripheral blood. Actively dividing cells accounted for less than 1% of the total T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with SF or in a hypoxic environment did not affect the expression of markers of T-cell activation. T cells from the SF of patients with JIA were highly differentiated and expressed early and late markers of activation with little evidence of in situ proliferation. This observation refines and extends previous reports of the SF T-cell phenotype in JIA and may have important implications for our understanding of chronic inflammation. 相似文献
148.
149.
Aoki M Schetter C Himly M Batista O Chang HW Vogt PK 《The Journal of biological chemistry》2000,275(9):6267-6275
The retroviral oncogene p3k (v-p3k) of avian sarcoma virus 16 (ASV16) codes for the catalytic subunit of phosphoinositide (PI) 3-kinase, p110alpha. The v-P3k protein is oncogenic in vivo and in vitro; its cellular counterpart, c-P3k, lacks oncogenicity. Fusion of viral Gag sequences to the amino terminus of c-P3k activates the transforming potential. Activation can also be achieved by the addition of a myristylation signal to the amino terminus or of a farnesylation signal to the carboxyl terminus of c-P3k. A mutated myristylation signal was equally effective; it also caused a strong increase in the kinase activity of P3k. Mutations that inactivate lipid kinase activity abolish oncogenicity. The transforming activity of P3k is correlated with the ability to induce activating phosphorylation in Akt. Point mutations and amino-terminal deletions recorded in v-P3k were shown to be irrelevant to the activation of oncogenic potential. Interactions of P3k with the regulatory subunit of PI 3-kinase, p85, or with Ras are not required for transformation. These results support the conclusion that the oncogenicity of P3k depends on constitutive lipid kinase activity. Akt is an important and probably essential downstream component of the oncogenic signal from P3k. 相似文献
150.
ABSTRACT: Co-evolving positions within protein sequences have been used as spatial constraints to develop a computational approach for modeling membrane protein structures. 相似文献