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181.
182.
Establishment of the Dorso-ventral Axis in Xenopus Embryos Is Presaged by Early Asymmetries in β-Catenin That Are Modulated by the Wnt Signaling Pathway 下载免费PDF全文
Carolyn A. Larabell Monica Torres Brian A. Rowning Cynthia Yost Jeffrey R. Miller Mike Wu David Kimelman Randall T. Moon 《The Journal of cell biology》1997,136(5):1123-1136
Eggs of Xenopus laevis undergo a postfertilization cortical rotation that specifies the position of the dorso-ventral axis and activates a transplantable dorsal-determining activity in dorsal blastomeres by the 32-cell stage. There have heretofore been no reported dorso-ventral asymmetries in endogenous signaling proteins that may be involved in this dorsal-determining activity during early cleavage stages. We focused on β-catenin as a candidate for an asymmetrically localized dorsal-determining factor since it is both necessary and sufficient for dorsal axis formation. We report that β-catenin displays greater cytoplasmic accumulation on the future dorsal side of the Xenopus embryo by the two-cell stage. This asymmetry persists and increases through early cleavage stages, with β-catenin accumulating in dorsal but not ventral nuclei by the 16- to 32cell stages. We then investigated which potential signaling factors and pathways are capable of modulating the steady-state levels of endogenous β-catenin. Steadystate levels and nuclear accumulation of β-catenin increased in response to ectopic Xenopus Wnt-8 (Xwnt-8) and to the inhibition of glycogen synthase kinase-3, whereas neither Xwnt-5A, BVg1, nor noggin increased β-catenin levels before the mid-blastula stage. As greater levels and nuclear accumulation of β-catenin on the future dorsal side of the embryo correlate with the induction of specific dorsal genes, our data suggest that early asymmetries in β-catenin presage and may specify dorso-ventral differences in gene expression and cell fate. Our data further support the hypothesis that these dorso-ventral differences in β-catenin arise in response to the postfertilization activation of a signaling pathway that involves Xenopus glycogen synthase kinase-3. 相似文献
183.
Synonymous substitution rates in mitochondrial and nuclear genes of Drosophila were compared. To make accurate comparisons, we considered the following: (1) relative synonymous rates, which do not require
divergence time estimates, should be used; (2) methods estimating divergence should take into account base composition; (3)
only very closely related species should be used to avoid effects of saturation; (4) the heterogeneity of rates should be
examined. We modified the methods estimating synonymous substitution numbers to account for base composition bias. By using
these methods, we found that mitochondrial genes have 1.7–3.4 times higher synonymous substitution rates than the fastest
nuclear genes or 4.5–9.0 times higher rates than the average nuclear genes. The average rate of synonymous transversions was
2.7 (estimated from the melanogaster species subgroup) or 2.9 (estimated from the obscura group) times higher in mitochondrial genes than in nuclear genes. Synonymous transversions in mitochondrial genes occurred
at an approximately equivalent rate to those in the fastest nuclear genes. This last result is not consistent with the hypothesis
that the difference in turnover rates between mitochondrial and nuclear genomes is the major factor determining higher synonymous
substitution rates in mtDNA. We conclude that the difference in synonymous substitution rates is due to a combination of two
factors: a higher transitional mutation rate in mtDNA and constraints on nuclear genes due to selection for codon usage.
Received: 27 November 1996 / Accepted: 8 May 1997 相似文献
184.
Although bacterial species display wide variation in their overall GC contents, the genes within a particular species' genome
are relatively similar in base composition. As a result, sequences that are novel to a bacterial genome—i.e., DNA introduced
through recent horizontal transfer—often bear unusual sequence characteristics and can be distinguished from ancestral DNA.
At the time of introgression, horizontally transferred genes reflect the base composition of the donor genome; but, over time,
these sequences will ameliorate to reflect the DNA composition of the new genome because the introgressed genes are subject
to the same mutational processes affecting all genes in the recipient genome. This process of amelioration is evident in a
large group of genes involved in host-cell invasion by enteric bacteria and can be modeled to predict the amount of time required
after transfer for foreign DNA to resemble native DNA. Furthermore, models of amelioration can be used to estimate the time
of introgression of foreign genes in a chromosome. Applying this approach to a 1.43-megabase continuous sequence, we have
calculated that the entire Escherichia coli chromosome contains more than 600 kb of horizontally transferred, protein-coding DNA. Estimates of amelioration times indicate
that this DNA has accumulated at a rate of 31 kb per million years, which is on the order of the amount of variant DNA introduced
by point mutations. This rate predicts that the E. coli and Salmonella enterica lineages have each gained and lost more than 3 megabases of novel DNA since their divergence.
Received: 7 July 1996 / Accepted: 27 September 1996 相似文献
185.
Ribosomal DNA and ITS-2 sequence comparisons as a tool for predicting genetic relatedness 总被引:14,自引:0,他引:14
The determination of the secondary structure of the internal transcribed spacer (ITS) regions separating nuclear ribosomal
RNA genes of Chlorophytes has improved the fidelity of alignment of nuclear ribosomal ITS sequences from related organisms.
Application of this information to sequences from green algae and plants suggested that a subset of the ITS-2 positions is
relatively conserved. Organisms that can mate are identical at all of these 116 positions, or differ by at most, one nucleotide
change. Here we sequenced and compared the ITS-1 and ITS-2 of 40 green flagellates in search of the nearest relative to Chlamydomonas reinhardtii. The analysis clearly revealed one unique candidate, C. incerta. Several ancillary benefits of the analysis included the identification of mislabelled cultures, the resolution of confusion
concerning C. smithii, the discovery of misidentified sequences in GenBank derived from a green algal contaminant, and an overview of evolutionary
relationships among the Volvocales, which is congruent with that derived from rDNA gene sequence comparisons but improves
upon its resolution. The study further delineates the taxonomic level at which ITS sequences, in comparison to ribosomal gene
sequences, are most useful in systematic and other studies.
Received: 14 February 1997 / Accepted: 28 March 1997 相似文献
186.
The Lipid Peroxidation Product, 4-Hydroxy-2-trans-Nonenal, Alters the Conformation of Cortical Synaptosomal Membrane Proteins 总被引:6,自引:1,他引:5
‡Ram Subramaniam ‡Fred Roediger Brad Jordan †‡§Mark P. Mattson §Jeffrey N. Keller Georg Waeg ‡§ D. Allan Butterfield 《Journal of neurochemistry》1997,69(3):1161-1169
Abstract: Alzheimer's disease (AD) is widely held to be a disorder associated with oxidative stress due, in part, to the membrane action of amyloid β-peptide (Aβ). Aβ-associated free radicals cause lipid peroxidation, a major product of which is 4-hydroxy-2- trans -nonenal (HNE). We determined whether HNE would alter the conformation of synaptosomal membrane proteins, which might be related to the known neurotoxicity of Aβ and HNE. Electron paramagnetic resonance spectroscopy, using a protein-specific spin label, MAL-6(2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl), was used to probe conformational changes in gerbil cortical synaptosomal membrane proteins, and a lipid-specific stearic acid label, 5-nitroxide stearate, was used to probe for HNE-induced alterations in the fluidity of the bilayer domain of these membranes. Synaptosomal membranes, incubated with low concentrations of HNE, exhibited changes in protein conformation and bilayer order and motion (fluidity). The changes in protein conformation were found to be concentration- and time-dependent. Significant protein conformational changes were observed at physiologically relevant concentrations of 1–10 µ M HNE, reminiscent of similar changes in synaptosomal membrane proteins from senile plaque- and Aβ-rich AD hippocampal and inferior parietal brain regions. HNE-induced modifications in the physical state of gerbil synaptosomal membrane proteins were prevented completely by using excess glutathione ethyl ester, known to protect neurons from HNE-caused neurotoxicity. Membrane fluidity was found to increase at higher concentrations of HNE (50 µ M ). The results obtained are discussed with relevance to the hypothesis of Aβ-induced free radical-mediated lipid peroxidation, leading to subsequent HNE-induced alterations in the structure and function of key membrane proteins with consequent neurotoxicity in AD brain. 相似文献
187.
†Heather Prince Miller †Allan I. Levey ‡Jeffrey D. Rothstein Anastassios V. Tzingounis P. Jeffrey Conn 《Journal of neurochemistry》1997,68(4):1564-1570
Abstract: There is increasing evidence that levels of glutamate are elevated in certain brain regions immediately prior to and during induction and propagation of seizures. Modulation of high-affinity glutamate uptake is a potential mechanism responsible for the elevated levels observed with seizures. To date, three distinct Na+ -dependent glutamate transporters have been cloned from rat and rabbit: GLT-1, GLAST, and EAAC-1. We performed a series of experiments to determine whether levels of these transporters are altered in amygdala-kindled rats. Levels of GLT-1, GLAST, and EAAC-1 were examined in three brain regions (hippocampus, piriform cortex/amygdala, and limbic forebrain) by quantitative immunoblotting using subtype-specific antibodies. GLAST protein was down-regulated in the piriform cortex/amygdala region of kindled rats as early as 24 h after one stage 3 seizure and persisting through multiple stage 5 seizures. In contrast, kindling induced an increase in EAAC-1 levels in piriform cortex/amygdala and hippocampus once the animals had reached the stage 5 level. No changes in GLT-1 were observed in any region examined. Changes in transporter levels could contribute to the changes in glutamate levels seen with kindling. 相似文献
188.
The impact of air perfusion on the endothelial function of the rat mesenteric arterial bed (MAB; perfused with Krebs' bicarbonate plus indomethacin) was compared to that of the NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME). Air shifted the dose-response curve for the alpha-adrenoceptor agonist, norepinephrine (NE) to the left (ED50%: 2.9 ± 0.7 to 0.9 ± 0.7 μg, P < 0.05); maximal vasoconstriction did not change. L-NAME produced a similar increase in midrange sensitivity (ED50% 1.4 ± 0.7 μg, P < 0.05) and a 20% increase in maximum (152 ± 6 to 183 ± 7 mmHg, P < 0.05). Electromechanical stimulation with potassium chloride (KCL) was not modified by reserpine. Neither air nor L-NAME modified midrange sensitivity to KCL. L-NAME produced a 17% increase in maximum (91 ± 4 to 107 ± 5 mmHg, P < 0.05); reserpine abolished the latter effect. Air and L-NAME diminished endothelium-dependent vasodilation elicited by carbachol. Air did not modify endothelium-dependent vasodilation elicited by sodium nitroprusside; this response was potentiated by L-NAME. In summary, air and L-NAME produced similar effects on receptor-dependent activation of the endothelial L-arginine nitric oxide (NO) pathway. Potentiation by L-NAME of the maximal electromechanical response suggests the existence of a tone-dependent NO system. Abolition of the latter response by reserpine suggests that this system is of sympathetic origin. 相似文献
189.
Dirofilaria immitis: heartworm infection alters pulmonary artery endothelial cell behavior 总被引:1,自引:0,他引:1
Mupanomunda Maria; Williams Jeffrey F.; Mackenzie Charles D.; Kaiser Lana 《Journal of applied physiology》1997,82(2):389-398
Mupanomunda, Maria, Jeffrey F. Williams, Charles D. Mackenzie, and Lana Kaiser. Dirofilaria immitis:heartworm infection alters pulmonary artery endothelial cell behavior.J. Appl. Physiol. 82(2): 389-398, 1997.Thepathogenesis of filariasis has generally been attributed to eitherphysical presence of the adult parasites or the host's immune responseto the parasites. However, the spectrum of filariasis cannot beentirely explained by these causes, and other mechanisms must beoperative. It is now evident that factors released by filarialparasites likely contribute to the pathogenesis of filarial diseases.Adult heartworms (Dirofilaria immitis) reside in the rightheart and pulmonary artery, so the pulmonary artery should be exposedto the highest concentration of filarial factors. We tested thehypothesis that endothelium-dependent relaxation is altered in the invitro pulmonary artery from heartworm-infected dogs. Relaxationresponses to endothelium-dependent vasodilators (methacholine,bradykinin, substance P, and A-23187) and the non-endothelium-dependent vasodilator nitroglycerin and contractile responses were measured inrings of pulmonary artery from control and heartworm-infected dogs.Endothelium-dependent relaxation was assessed in the presence andabsence of inhibitors of nitric oxide synthase, cyclooxygenase, andguanylate cyclase. Responses to methacholine, substance P, and A-23187,but not to bradykinin, nitroglycerin, norepinephrine, or KCl, weredepressed in pulmonary artery from heartworm-infected dogs whencompared with control, suggesting that changes in endothelial cell andnot vascular smooth muscle behavior are involved in altered relaxation.The mechanism of endothelium-dependent relaxation in control pulmonaryartery appears to involve nitric oxide in the case of methacholine andboth nitric oxide and a cyclooxygenase product in the case ofbradykinin and A-23187. The mechanism of endothelium-dependentrelaxation in pulmonary artery from heartworm-infected dogs was notclearly elucidated. These data provide no evidence that heartworminfection globally influences either endothelial cell receptor functionor the vascular smooth muscle guanylate cyclase guanosine 3,5-cyclicmonophosphate system, making it likely that changes in intracellularsignaling are primarily responsible for the observed alteration ofendothelium-mediated relaxation. Alteration of endothelial cellfunction by filarial parasites may be an important component inthe pathology associated with filariasis. 相似文献
190.
Jeffrey K. McKee J. Francis Thackeray Lee R. Berger 《American journal of physical anthropology》1995,96(3):235-250
Fossil assemblages from the Pliocene and Pleistocene of southern Africa were seriated in order to give a better idea of their relative chronology. Time-sensitive mammals were selected for calculation of the Faunal Resemblance Index among 17 site units. On the basis of a logistical seriation and subsequent site analysis, the following sequence of sites was deemed most probable: Makapansgat Member 3, Makapansgat Member 4, Taung Dart deposits, Sterkfontein Member 4 and Taung Hrdli?ka deposits, Sterkfontein Member 5 (in part) and Kromdraai B, Kromdraai A and Swartkrans Member 1, Swartkrans Member 2, Swartkrans Member 3, Plovers Lake, Cornelia, Elandsfontein Main Site, Cave of Hearths Acheulian levels, Florisbad and Equus Cave and Klasies River Mouth. © 1995 Wiley-Liss, Inc. 相似文献