排序方式: 共有52条查询结果,搜索用时 15 毫秒
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Olaf Weber Hilmar Bischoff Carsten Schmeck Michael-Friedrich Böttcher 《Cellular and molecular life sciences : CMLS》2010,67(18):3139-3149
Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from
the atheroprotective high density lipoprotein (HDL) to the proatherogenic low density lipoprotein cholesterol (LDL) and very
low density lipoprotein cholesterol (VLDL) leading to lower levels of HDL but raising the levels of proatherogenic LDL and
VLDL. Inhibition of CETP is considered a potential approach to treat dyslipidemia. However, discussions regarding the role
of CETP-mediated lipid transfer in the development of atherosclerosis and CETP inhibition as a potential strategy for prevention
of atherosclerosis have been controversial. Although many animal studies support the hypothesis that inhibition of CETP activity
may be beneficial, negative phase III studies on clinical endpoints with the CETP inhibitor torcetrapib challenged the future
perspectives of CETP inhibitors as potential therapeutic agents. The review provides an update on current understanding of
the molecular mechanisms involved in CETP activity and its inhibition. 相似文献
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Boyman O Krieg C Homann D Sprent J 《Cellular and molecular life sciences : CMLS》2012,69(10):1597-1608
Homeostasis in the immune system encompasses the mechanisms governing maintenance of a functional and diverse pool of lymphocytes, thus guaranteeing immunity to pathogens while remaining self-tolerant. Antigen-naïve T cells rely on survival signals through contact with self-peptide-loaded major histocompatibility complex (MHC) molecules plus interleukin (IL)-7. Conversely, antigen-experienced (memory) T cells are typically MHC-independent and they survive and undergo periodic homeostatic proliferation through contact with both IL-7 and IL-15. Also, non-conventional γδ T cells rely on a mix of IL-7 and IL-15 for their homeostasis, whereas natural killer cells are mainly dependent on contact with IL-15. Homeostasis of CD4+ T regulatory cells is different in being chiefly regulated by contact with IL-2. Notably, increased levels of these cytokines cause expansion of responsive lymphocytes, such as found in lymphopenic hosts or following cytokine injection, whereas reduced cytokine levels cause a decline in cell numbers. 相似文献
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Lee JH Huynh M Silhavy JL Kim S Dixon-Salazar T Heiberg A Scott E Bafna V Hill KJ Collazo A Funari V Russ C Gabriel SB Mathern GW Gleeson JG 《Nature genetics》2012,44(8):941-945
De novo somatic mutations in focal areas are well documented in diseases such as neoplasia but are rarely reported in malformation of the developing brain. Hemimegalencephaly (HME) is characterized by overgrowth of either one of the two cerebral hemispheres. The molecular etiology of HME remains a mystery. The intractable epilepsy that is associated with HME can be relieved by the surgical treatment hemispherectomy, allowing sampling of diseased tissue. Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with HME (n = 20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes. A recurrent PIK3CA c.1633G>A mutation was found in four separate cases. Identified mutations were present in 8-40% of sequenced alleles in various brain regions and were associated with increased neuronal S6 protein phosphorylation in the brains of affected individuals, indicating aberrant activation of mammalian target of rapamycin (mTOR) signaling. Thus HME is probably a genetically mosaic disease caused by gain of function in phosphatidylinositol 3-kinase (PI3K)-AKT3-mTOR signaling. 相似文献
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William O.C. Symondson Jeremy D. Holloway Benoit Goossens Carsten T. Müller 《Journal of Natural History》2015,49(9-10):553-560
Many Lepidoptera larvae use pieces of vegetation bound with silk to construct or disguise their cocoons. Here we report the first known case of a caterpillar building its cocoon entirely out of fragments of resin, broken away from sheets of dried resin on the trunk of a tree and held together with silk. The behaviour of the larva (possibly Negritothripa sp. in the Nolidae), from the Kinabatangan Wildlife Sanctuary in Sabah, Borneo, is described. The cocoon was constructed on the trunk of Vatica rassak (Dipterocarpaceae). Analysis of resin from the cocoon, using gas chromatography-mass spectrometry, revealed a complex mixture of 260 components, dominated by sesquiterpenes and triterpenes. Many of these compounds have defensive properties, protecting the tree from herbivores and fungi. The larva appears to have evolved an elaborate and possibly unique behaviour, allowing it to harness the defensive properties of the resin to protect its pupa from predators and/or entomopathogenic fungi. 相似文献
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Marsicano G Wotjak CT Azad SC Bisogno T Rammes G Cascio MG Hermann H Tang J Hofmann C Zieglgänsberger W Di Marzo V Lutz B 《Nature》2002,418(6897):530-534
Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction, its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1) and endocannabinoids are present in memory-related brain areas and modulate memory. Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex, a region known to control extinction of aversive memories. In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala. 相似文献
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René Chester Goduscheit Carsten Bergenholtz Jacob Høj Jørgensen Erik S. Rasmussen 《Systemic Practice and Action Research》2008,21(4):267-281
This article addresses the distinct ethical challenges of action research in inter-organisational projects. Traditionally, the literature on action research has distinguished between two researcher roles: The problem-solver and the observer. Based on an action research project in a Danish inter-organisational network, a third role as legitimiser is identified as an ethical challenge. Potentially, the legitimacy that the researchers carry as academic knowledge-generating actors may be used by a particular company to involve other companies in the network. Thus, the researchers may be perceived as bringing into the other organisations a Trojan Horse containing the interests of this particular company. Lack of clarity in defining the role of the action researcher may thus jeopardise the trustworthiness of the researchers and the action research project. On the basis of the case study analysis, the article develops a number of preliminary points of ethical consideration for future research analysis. 相似文献
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Dynamic molecular processes mediate cellular mechanotransduction 总被引:1,自引:0,他引:1
Cellular responses to mechanical forces are crucial in embryonic development and adult physiology, and are involved in numerous diseases, including atherosclerosis, hypertension, osteoporosis, muscular dystrophy, myopathies and cancer. These responses are mediated by load-bearing subcellular structures, such as the plasma membrane, cell-adhesion complexes and the cytoskeleton. Recent work has demonstrated that these structures are dynamic, undergoing assembly, disassembly and movement, even when ostensibly stable. An emerging insight is that transduction of forces into biochemical signals occurs within the context of these processes. This framework helps to explain how forces of varying strengths or dynamic characteristics regulate distinct signalling pathways. 相似文献