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LSD as an agonist and antagonist at central dopamine receptors 总被引:1,自引:0,他引:1
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Females express mate preferences for genetically dissimilar males, especially with respect to the major histocompatibility complex, MHC, and for males whose sexually selected signals indicate high genetic quality. The balance of selection pressure on each trait will depend on how females weight these desirable qualities under different conditions, but this has not been tested empirically. Here we show in mice that although MHC dissimilarity and a 'good genes' indicator (investment in scent-marking) both have a role in determining female preference, their relative influence can vary depending on the degree of variability in each trait among available males. Such interactions between condition-dependent and disassortative mate choice criteria suggest a mechanism by which female choice can contribute to maintenance of additive genetic variance in both the MHC and condition-dependent traits, even under consistent directional selection. 相似文献
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Thayer SP di Magliano MP Heiser PW Nielsen CM Roberts DJ Lauwers GY Qi YP Gysin S Fernández-del Castillo C Yajnik V Antoniu B McMahon M Warshaw AL Hebrok M 《Nature》2003,425(6960):851-856
Hedgehog signalling--an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer--may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis. 相似文献
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McGregor L Makela V Darling SM Vrontou S Chalepakis G Roberts C Smart N Rutland P Prescott N Hopkins J Bentley E Shaw A Roberts E Mueller R Jadeja S Philip N Nelson J Francannet C Perez-Aytes A Megarbane A Kerr B Wainwright B Woolf AS Winter RM Scambler PJ 《Nature genetics》2003,34(2):203-208
Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero. 相似文献
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Summary High concentrations of bethanechol (10–4 to 10–3 M) were effective stimulants of amylase secretion from the mouse pancreas if incubations are performed in low [ca2+] (0.1 mM) solutions but not if normal Krebs solution (2.56 mM Ca2+) was used. This inhibitory effect of Ca2+ at high secretagogue concentrations did not appear to be mediated through the microtubules or microfilaments. 相似文献