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排序方式: 共有544条查询结果,搜索用时 31 毫秒
461.
Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.  相似文献   
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SR Waitukaitis  HM Jaeger 《Nature》2012,487(7406):205-209
Although liquids typically flow around intruding objects, a counterintuitive phenomenon occurs in dense suspensions of micrometre-sized particles: they become liquid-like when perturbed lightly, but harden when driven strongly. Rheological experiments have investigated how such thickening arises under shear, and linked it to hydrodynamic interactions or granular dilation. However, neither of these mechanisms alone can explain the ability of suspensions to generate very large, positive normal stresses under impact. To illustrate the phenomenon, such stresses can be large enough to allow a person to run across a suspension without sinking, and far exceed the upper limit observed under shear or extension. Here we show that these stresses originate from an impact-generated solidification front that transforms an initially compressible particle matrix into a rapidly growing jammed region, ultimately leading to extraordinary amounts of momentum absorption. Using high-speed videography, embedded force sensing and X-ray imaging, we capture the detailed dynamics of this process as it decelerates a metal rod hitting a suspension of cornflour (cornstarch) in water. We develop a model for the dynamic solidification and its effect on the surrounding suspension that reproduces the observed behaviour quantitatively. Our findings suggest that prior interpretations of the impact resistance as dominated by shear thickening need to be revisited.  相似文献   
465.
Anomalous X-ray pulsars (AXPs) are slowly rotating neutron stars with very bright and highly variable X-ray emission that are believed to be powered by ultra-strong magnetic fields of >10(14) G, according to the 'magnetar' model. The radio pulsations that have been observed from more than 1,700 neutron stars with weaker magnetic fields have never been detected from any of the dozen known magnetars. The X-ray pulsar XTE J1810-197 was revealed (in 2003) as the first AXP with transient emission when its luminosity increased 100-fold from the quiescent level; a coincident radio source of unknown origin was detected one year later. Here we show that XTE J1810-197 emits bright, narrow, highly linearly polarized radio pulses, observed at every rotation, thereby establishing that magnetars can be radio pulsars. There is no evidence of radio emission before the 2003 X-ray outburst (unlike ordinary pulsars, which emit radio pulses all the time), and the flux varies from day to day. The flux at all radio frequencies is approximately equal--and at >20 GHz XTE J1810-197 is currently the brightest neutron star known. These observations link magnetars to ordinary radio pulsars, rule out alternative accretion models for AXPs, and provide a new window into the coronae of magnetars.  相似文献   
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Multiferroic and magnetoelectric materials   总被引:7,自引:0,他引:7  
Eerenstein W  Mathur ND  Scott JF 《Nature》2006,442(7104):759-765
A ferroelectric crystal exhibits a stable and switchable electrical polarization that is manifested in the form of cooperative atomic displacements. A ferromagnetic crystal exhibits a stable and switchable magnetization that arises through the quantum mechanical phenomenon of exchange. There are very few 'multiferroic' materials that exhibit both of these properties, but the 'magnetoelectric' coupling of magnetic and electrical properties is a more general and widespread phenomenon. Although work in this area can be traced back to pioneering research in the 1950s and 1960s, there has been a recent resurgence of interest driven by long-term technological aspirations.  相似文献   
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Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R). Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH-MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r(e/e) mice. However, pigmentation could be rescued by topical application of the cyclic AMP agonist forskolin, without the need for ultraviolet light, demonstrating that the pigmentation machinery is available despite the absence of functional MC1R. This chemically induced pigmentation was protective against ultraviolet-light-induced cutaneous DNA damage and tumorigenesis when tested in the cancer-prone, xeroderma-pigmentosum-complementation-group-C-deficient genetic background. These data emphasize the essential role of intercellular MSH signalling in the tanning response, and suggest a clinical strategy for topical small-molecule manipulation of pigmentation.  相似文献   
469.
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.  相似文献   
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