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81.
Summary Preweaning malnutrition permanently reduced brain size and cellular content but in spite of changes in the adrenocortical stress response no learning deficit was observed. Differential rearing environments did not influence the effects of malnutrition.This work was supported by a grant from the National Health and Medical Research Council of Australia.We thank Mrs.Jean Williams andDr. A. Miller, Department Maths. Stats., C. S. I. R. O., Sydney for assistance with the statistical analysis. 相似文献
82.
Grimson A Srivastava M Fahey B Woodcroft BJ Chiang HR King N Degnan BM Rokhsar DS Bartel DP 《Nature》2008,455(7217):1193-1197
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The LDL receptor pathway delivers arachidonic acid for eicosanoid formation in cells stimulated by platelet-derived growth factor 总被引:4,自引:0,他引:4
A J Habenicht P Salbach M Goerig W Zeh U Janssen-Timmen C Blattner W C King J A Glomset 《Nature》1990,345(6276):634-636
Animal cells can convert 20-carbon polyunsaturated fatty acids into prostaglandins (PGs) and leukotrienes. These locally produced mediators of inflammatory and immunological reactions act in an autocrine or paracrine fashion. Arachidonic acid (AA), the precursor of most PGs and leukotrienes, is present in the form of lipid esters within plasma lipoproteins and cannot be synthesised de novo by animal cells. Therefore, AA or its plant-derived precursor, linoleic acid, must be provided to cells if PGs or leukotrienes are to be formed. Because several classes of lipoproteins, including low-density lipoproteins (LDL), very-low-density lipoproteins, and chylomicron remnants, are taken up by means of the LDL receptor, and because LDL and very-low-density lipoproteins, but not high-density lipoproteins, stimulate PG synthesis, we have suggested previously that PG formation is directly linked to the LDL pathway. Using fibroblasts with the receptor-negative phenotype of familial hypercholesterolaemia and anti-LDL receptor antibodies, we show here that LDL deliver AA for PG production and that an LDL receptor-dependent feedback mechanism inhibits the activity of PGH synthase, the rate-limiting enzyme of PG synthesis. These results indicate that the LDL pathway has a regulatory role in PG synthesis, in addition to its well-known role in the maintenance of cellular cholesterol homeostasis. 相似文献
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Bohlen CJ Chesler AT Sharif-Naeini R Medzihradszky KF Zhou S King D Sánchez EE Burlingame AL Basbaum AI Julius D 《Nature》2011,479(7373):410-414
Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH < 6.5), MitTx massively potentiates (>100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception. 相似文献
89.
The ELF4-ELF3-LUX complex links the circadian clock to diurnal control of hypocotyl growth 总被引:1,自引:0,他引:1
Nusinow DA Helfer A Hamilton EE King JJ Imaizumi T Schultz TF Farré EM Kay SA 《Nature》2011,475(7356):398-402
90.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma 总被引:1,自引:0,他引:1
Varela I Tarpey P Raine K Huang D Ong CK Stephens P Davies H Jones D Lin ML Teague J Bignell G Butler A Cho J Dalgliesh GL Galappaththige D Greenman C Hardy C Jia M Latimer C Lau KW Marshall J McLaren S Menzies A Mudie L Stebbings L Largaespada DA Wessels LF Richard S Kahnoski RJ Anema J Tuveson DA Perez-Mancera PA Mustonen V Fischer A Adams DJ Rust A Chan-on W Subimerb C Dykema K Furge K Campbell PJ Teh BT Stratton MR Futreal PA 《Nature》2011,469(7331):539-542