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MDA-MB-231 human breast cancer cells have a survival signal generated by phospholipase D (PLD) that involves the activation of mTOR and MAP kinase. TGF-β signals that block cell cycle progression in G1 are suppressed in MDA-MB-231 cells. We report here that the elevated PLD activity in MDA-MB-231 cells suppresses TGF-β signaling. Suppression of PLD activity or PLD expression resulted in increased phosphorylation of Smad2 and Smad3 on Ser 465/467 – sites on Smads that get phosphorylated by the TGF-β receptor and positively regulate TGF-β signaling. The effect of PLD suppression on Smad2/3 phosphorylation was dependent on the presence of TGF-β. Suppression of PLD also suppressed phosphorylation of Smad2 on Ser 245/250/255 – sites that are phosphorylated by MAP kinase and negatively regulate TGF-β signaling. Suppression of PLD also led to increased expression of the cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1, the expression of which is stimulated in response to TGF-β. Consistent with the elevated expression of CDK inhibitors, suppression of PLD also suppressed phosphorylation of the CDK substrate pRb. Similar effects were also seen in PANC-1 human pancreatic cancer cells. The data presented here indicate that the suppressed TGF-β signaling in MDA-MB-231 and perhaps many other human cancer cells is due to elevated PLD activity and mediated by mTOR and MAP kinase. These results indicate that the survival signals generated by PLD involve the suppression TGF-β signals that promote G1 arrest.  相似文献   

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The conservation problems affecting the endangered rodent Microtus cabrerae are mainly related to habitat loss and fragmentation. In the present study, we examined the presence/absence of the species in a group of potentially suitable habitat patches, and then evaluated the microhabitat attributes of locations used by wild-ranging individuals within occupied patches. Our results revealed that shallow flooding and abundant grass cover appear to be important factors in determining the presence among localities, but high rush cover strongly determined the presence and habitat use by voles both among and within localities. The preservation of these microhabitat characteristics may be required to effectively ensure the occurrence and stability of M. cabrerae colonies.  相似文献   

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Species of Coreidae (Heteroptera) cause ‘water soaked’ lesions in their food plants. Such insects typically feed from parenchyma in and surrounding vascular tissues and also cause acropetal wilting and necrosis of small diameter shoots. Feeding byMictis profana (Fabr.) in South Australia on the shoots ofAcacia iteaphylla F. Muell. ex Benth. was found to cause a local, concurrent increase in both water content and free amino acid concentration, consistent with phloem unloading. Coreids, unlike other groups of phytophagous Heteroptera, secrete a salivary sucrase (α-D-glucohydrolase, EC 3.2.1.48) as probably the sole salivary carbohydrase, and tissues attacked byM. profana showed more sucrose hydrolysing activity than unattacked. The salivary enzyme is postulated to cause unloading of solutes into the apoplast due to the osmotic effects of conversion of endogenous sucrose to glucose and fructose, allowing the insect to suck the leaked contents of many cells from a single locus. The term ‘osmotic pump feeding’ is proposed for such a process. In demonstrations of its feasibility, infiltration of shoots with mixtures of glucose and fructose stoichiometrically equivalent to isosmotic sucrose increased the amounts of tissue sap and amino acid that could be sucked from the tissues; similarly, invertase and 1 M sugars forced into the extracellular space of stem sections increased the amino acids offloaded into the bathing solutions.  相似文献   

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IT is now recognized that hydroxylated metabolites of vitamin D (that is, cholecalciferol) function as effectors of the physiological actions originally attributed to the unaltered vitamin1. The activation of vitamin D by specific hydroxylation reactions and sequestration of the resultant metabolites by target tissues represents a hormonal control loop which is feed-back sensitive. 25-Hydroxycholecalciferol (25-HCC) and 1,25-dihydroxycholecalciferol (1,25-DHCC) have been shown to be participants in the control loop, vitamin D being first metabolized in the liver to 25-HCC2 which in turn is hydroxylated in the C-1 position to 1,25-DHCC in the kidney3,4. The metabolically active form in the intestine appears to be 1,25-DHCC5,6.  相似文献   

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In culture‐contact situations, it is commonplace for words to be borrowed from other unrelated vernaculars, for their pronunciations to be changed, and their meanings modified to fit new contexts. The Arandic word altyerre is a rather extreme example of this, and at the end of the nineteenth century, the ‘translation’ of the related word Alcheringa as ‘dream‐times’ sparked a debate that, in some forms, continues to this day. In this article, I discuss some of the reasons why this particular word struck such a controversial chord. I give an updated semantic perspective on the word altyerre , drawing on evidence from Arandic languages and from other languages in Central Australia. Then I examine some of the consequences of both religious and secular interpretations of altyerre and show how the popularisation of this word and its translations has impacted on its meanings in current usage.  相似文献   

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Defective colloids of blue MoOx nanosheets were prepared by anodizing exfoliation method in water. This colloidal solution exhibits an optical plasmonic absorption band in the infrared region at about 760 nm. Merely mixing HAuCl4 solution with the MoOx leads to loss of the blue color, decaying of 760 nm plasmonic peak and simultaneous formation of the gold plasmon absorption peak at 550–570 nm. Some spectral variations in gold plasmonic peak and MoOx optical band gap were observed for Mo:Au ratio of 10:1, 20:1, 30:1, and 40:1. The size of the gold nanoparticles was in the 5–6 nm range with fcc crystalline structure. X-ray photoelectron spectroscopy (XPS) revealed that the initial solution contains Mo5+ states and hydroxyl groups, which after reduction, hydroxyl groups are eliminated and the Mo5+ states converted to Mo6+. The obtained Au-MoO3 colloids have a gasochromic property in which they are colored back to blue in the presence of hydrogen gas and the molybdenum oxide absorption peak recovered again. Furthermore, it was observed that both gold and Mo oxide plasmonic peaks redshift by insertion of hydrogen gas which is attributed to change in solution refractive index and formation of defect concentration.  相似文献   

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It is common knowledge that macromolecular crystals are damaged by the X‐rays they are exposed to during conventional data collection. One of the claims made about the crystallographic data collection now being collected using X‐ray free‐electron lasers (XFEL) is that they are unaffected by radiation damage. XFEL data sets are assembled by merging data obtained from a very large number of crystals, each of which is exposed to a single femtosecond pulse of radiation, the duration of which is so short that diffraction occurs before the damage done to the crystal has time to become manifest, i.e. “diffraction‐before‐destruction.” However, recent theoretical studies have shown that many of the elemental electronic processes that ultimately result in the destruction of such crystals occur during a single pulse. It is predicted that the amplitudes of atomic scattering factor could be reduced by as much as 75% within the first 5 femtoseconds of such pulses, and that different atoms will respond in different ways. Experimental evidence is provided here that these predictions are correct.  相似文献   

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