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Primordial germ cell migration 总被引:10,自引:0,他引:10
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Edgcomb VP Molyneaux SJ Böer S Wirsen CO Saito M Atkins MS Lloyd K Teske A 《Extremophiles : life under extreme conditions》2007,11(2):329-342
Growth and survival of hyperthermophilic archaea in their extreme hydrothermal vent and subsurface environments are controlled
by chemical and physical key parameters. This study examined the effects of elevated sulfide concentrations, temperature,
and acidic pH on growth and survival of two hydrothermal vent archaea (Pyrococcus strain GB-D and Thermococcus fumicolans) under high temperature and pressure regimes. These two strains are members of the Thermococcales, a family of hyperthermophilic,
heterotrophic, sulfur-reducing archaea that occur in high densities at vent sites. As actively growing cells, these two strains
tolerated regimes of pH, pressure, and temperature that were in most cases not tolerated under severe substrate limitation.
A moderate pH of 5.5–7 extends their survival and growth range over a wider range of sulfide concentrations, temperature and
pressure, relative to lower pH conditions. T. fumicolans and Pyrococcus strain GB-D grew under very high pressures that exceeded in-situ pressures typical of hydrothermal vent depths, and included
deep subsurface pressures. However, under the same conditions, but in the absence of carbon substrates and electron acceptors,
survival was generally lower, and decreased rapidly when low pH stress was combined with high pressure and high temperature.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
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Fobian YM Freskos JN Barta TE Bedell LJ Heintz R Kassab DJ Kiefer JR Mischke BV Molyneaux JM Mullins P Munie GE Becker DP 《Bioorganic & medicinal chemistry letters》2011,21(10):2823-2825
Continuing our interest in designing compounds preferentially potent and selective for MMP-13, we report on a series of hydroxamic acids with a flexible amide P1′ substituents. We identify an amide which spares both MMP-1 and -14, and shows >500 fold selectivity for MMP-13 versus MMP-2 and -8. 相似文献
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Robert O. Hughes John K. Walker D. Joseph Rogier Steve E. Heasley Rhadika M. Blevis-Bal Alan G. Benson E. Jon Jacobsen Jerry W. Cubbage Yvette M. Fobian Dafydd R. Owen John N. Freskos John M. Molyneaux David L. Brown Brad A. Acker Todd M. Maddux Mike B. Tollefson Joseph B. Moon Brent V. Mischke Jeanne M. Rumsey Yi Zheng Ying Yu 《Bioorganic & medicinal chemistry letters》2009,19(17):5209-5213
We describe efforts to improve the pharmacokinetic profile of the aminopyridopyrazinone class of PDE5 inhibitors. These efforts led to the discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent and selective inhibitor of PDE5 with an excellent PK profile. 相似文献
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The pro-apoptotic gene Bax is required for the death of ectopic primordial germ cells during their migration in the mouse embryo 总被引:3,自引:0,他引:3
Stallock J Molyneaux K Schaible K Knudson CM Wylie C 《Development (Cambridge, England)》2003,130(26):6589-6597
In the mouse embryo, significant numbers of primordial germ cells (PGCs) fail to migrate correctly to the genital ridges early in organogenesis. These usually die in ectopic locations. In humans, 50% of pediatric germ line tumors arise outside the gonads, and these are thought to arise from PGCs that fail to die in ectopic locations. We show that the pro-apoptotic gene Bax, previously shown to be required for germ cell death during later stages of their differentiation in the gonads, is also expressed during germ cell migration, and is required for the normal death of germ cells left in ectopic locations during and after germ cell migration. In addition, we show that Bax is downstream of the known cell survival signaling interaction mediated by the Steel factor/Kit ligand/receptor interaction. Together, these observations identify the major mechanism that removes ectopic germ cells from the embryo at early stages. 相似文献
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Edgcomb VP Molyneaux SJ Saito MA Lloyd K Böer S Wirsen CO Atkins MS Teske A 《Applied and environmental microbiology》2004,70(4):2551-2555
The chemical stress factors for microbial life at deep-sea hydrothermal vents include high concentrations of heavy metals and sulfide. Three hyperthermophilic vent archaea, the sulfur-reducing heterotrophs Thermococcus fumicolans and Pyrococcus strain GB-D and the chemolithoautotrophic methanogen Methanocaldococcus jannaschii, were tested for survival tolerance to heavy metals (Zn, Co, and Cu) and sulfide. The sulfide addition consistently ameliorated the high toxicity of free metal cations by the formation of dissolved metal-sulfide complexes as well as solid precipitates. Thus, chemical speciation of heavy metals with sulfide allows hydrothermal vent archaea to tolerate otherwise toxic metal concentrations in their natural environment. 相似文献
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Skilton MR Lai NT Griffiths KA Molyneaux LM Yue DK Sullivan DR Celermajer DS 《American journal of physiology. Heart and circulatory physiology》2005,288(3):H1404-H1410
A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33 +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC 134 +/- 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = -0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance. 相似文献
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Takeuchi Y Molyneaux K Runyan C Schaible K Wylie C 《Development (Cambridge, England)》2005,132(24):5399-5409
Fibroblast growth factor (FGF) signaling is thought to play a role in germ cell behavior. FGF2 has been reported to be a mitogen for primordial germ cells in vitro, whilst combinations of FGF2, steel factor and LIF cause cultured germ cells to transform into permanent lines of pluripotent cells resembling ES cells. However, the actual function of FGF signaling on the migrating germ cells in vivo is unknown. We show, by RT-PCR analysis of cDNA from purified E10.5 germ cells, that germ cells express two FGF receptors: Fgfr1-IIIc and Fgfr2-IIIb. Second, we show that FGF-mediated activation of the MAP kinase pathway occurs in germ cells during their migration, and thus they are potentially direct targets of FGF signaling. Third, we use cultured embryo slices in simple gain-of-function experiments, using FGF ligands, to show that FGF2, a ligand for FGFR1-IIIc, affects motility, whereas FGF7, a ligand for FGFR2-IIIb, affects germ cell numbers. Loss of function, using a specific inhibitor of FGF signaling, causes increased apoptosis and inhibition of cell shape change in the migrating germ cells. Lastly, we confirm in vivo the effects seen in slice cultures in vitro, by examining germ cell positions and numbers in embryos carrying a loss-of-function allele of FGFR2-IIIb. In FGFR2-IIIb(-/-) embryos, germ cell migration is unaffected, but the numbers of germ cells are significantly reduced. These data show that a major role of FGF signaling through FGFR2-IIIb is to control germ cell numbers. The data do not discriminate between direct and indirect effects of FGF signaling on germ cells, and both may be involved. 相似文献