排序方式: 共有8条查询结果,搜索用时 187 毫秒
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One motivation in the study of development is the discovery of mechanisms that may guide evolutionary change. Here we report how development governs relative size and number of cheek teeth, or molars, in the mouse. We constructed an inhibitory cascade model by experimentally uncovering the activator-inhibitor logic of sequential tooth development. The inhibitory cascade acts as a ratchet that determines molar size differences along the jaw, one effect being that the second molar always makes up one-third of total molar area. By using a macroevolutionary test, we demonstrate the success of the model in predicting dentition patterns found among murine rodent species with various diets, thereby providing an example of ecologically driven evolution along a developmentally favoured trajectory. In general, our work demonstrates how to construct and test developmental rules with evolutionary predictability in natural systems. 相似文献
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Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope 总被引:1,自引:1,他引:0
Poonam Malik Nadia Korfali Vlastimil Srsen Vassiliki Lazou Dzmitry G. Batrakou Nikolaj Zuleger Deirdre M. Kavanagh Gavin S. Wilkie Martin W. Goldberg Eric C. Schirmer 《Cellular and molecular life sciences : CMLS》2010,67(8):1353-1369
Nuclear envelope complexity is expanding with respect to identification of protein components. Here we test the validity of
proteomics results that identified 67 novel predicted nuclear envelope transmembrane proteins (NETs) from liver by directly
comparing 30 as tagged fusions using targeting assays. This confirmed 21 as NETs, but 4 only targeted in certain cell types,
underscoring the complexity of interactions that tether NETs to the nuclear envelope. Four NETs accumulated at the nuclear
rim in normal fibroblasts but not in fibroblasts lacking lamin A, suggesting involvement of lamin A in tethering them in the
nucleus. However, intriguingly, for the NETs tested alternative mechanisms for nuclear envelope retention could be found in
Jurkat cells that normally lack lamin A. This study expands by a factor of three the number of liver NETs analyzed, bringing
the total confirmed to 31, and shows that several have multiple mechanisms for nuclear envelope retention. 相似文献
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Burguillos MA Deierborg T Kavanagh E Persson A Hajji N Garcia-Quintanilla A Cano J Brundin P Englund E Venero JL Joseph B 《Nature》2011,472(7343):319-324
Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-δ-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves. 相似文献
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Richards A van den Maagdenberg AM Jen JC Kavanagh D Bertram P Spitzer D Liszewski MK Barilla-Labarca ML Terwindt GM Kasai Y McLellan M Grand MG Vanmolkot KR de Vries B Wan J Kane MJ Mamsa H Schäfer R Stam AH Haan J de Jong PT Storimans CW van Schooneveld MJ Oosterhuis JA Gschwendter A Dichgans M Kotschet KE Hodgkinson S Hardy TA Delatycki MB Hajj-Ali RA Kothari PH Nelson SF Frants RR Baloh RW Ferrari MD Atkinson JP 《Nature genetics》2007,39(9):1068-1070
Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias. 相似文献
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Kavanagh M 《Nature》1972,239(5372):406-407
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