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121.
He XC Yin T Grindley JC Tian Q Sato T Tao WA Dirisina R Porter-Westpfahl KS Hembree M Johnson T Wiedemann LM Barrett TA Hood L Wu H Li L 《Nature genetics》2007,39(2):189-198
Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTEN-deficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin. Akt phosphorylates beta-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin. 相似文献
122.
Cyclic GMP is involved in the excitation of invertebrate photoreceptors 总被引:13,自引:0,他引:13
The hyperpolarizing receptor potential in vertebrate rod photoreceptors appears to be mediated by the second messenger, cyclic GMP. Injection of cGMP into rods or application of cGMP to inside-out membrane patches activates a conductance resembling that produced by light. Light produces a rapid reduction of cGMP in living rods, leading to closure of sodium channels and membrane hyperpolarization. In most invertebrate photoreceptors the response to light is depolarizing. We have investigated whether cGMP is involved in controlling the increase in sodium conductance that underlies this depolarization. We show here that injection of cGMP into Limulus photoreceptors produces a depolarization that mimics the receptor potential. We also show that the cGMP concentration of the squid retina increases rapidly during exposure to light. These results support the hypothesis that cGMP mediates the light-induced depolarization in invertebrate photoreceptors and suggests that vertebrate and invertebrate phototransduction may be more similar than previously thought. 相似文献
123.
124.
Until now, the analysis of burrowing mechanics has neglected the mechanical properties of impeding, muddy, cohesive sediments, which behave like elastic solids. Here we show that burrowers can progress through such sediments by using a mechanically efficient, previously unsuspected mechanism--crack propagation--in which an alternating 'anchor' system of burrowing serves as a wedge to extend the crack-shaped burrow. The force required to propagate cracks through sediment in this way is relatively small: we find that the force exerted by the annelid worm Nereis virens in making and moving into such a burrow amounts to less than one-tenth of the force it needs to use against rigid aquarium walls. 相似文献
125.
The genome of the social amoeba Dictyostelium discoideum 总被引:2,自引:0,他引:2
Eichinger L Pachebat JA Glöckner G Rajandream MA Sucgang R Berriman M Song J Olsen R Szafranski K Xu Q Tunggal B Kummerfeld S Madera M Konfortov BA Rivero F Bankier AT Lehmann R Hamlin N Davies R Gaudet P Fey P Pilcher K Chen G Saunders D Sodergren E Davis P Kerhornou A Nie X Hall N Anjard C Hemphill L Bason N Farbrother P Desany B Just E Morio T Rost R Churcher C Cooper J Haydock S van Driessche N Cronin A Goodhead I Muzny D Mourier T Pain A Lu M Harper D Lindsay R Hauser H James K Quiles M 《Nature》2005,435(7038):43-57
The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi. 相似文献
126.
After an earthquake, numerous smaller shocks are triggered over distances comparable to the dimensions of the mainshock fault rupture, although they are rare at larger distances. Here we analyse the scaling of dynamic deformations (the stresses and strains associated with seismic waves) with distance from, and magnitude of, their triggering earthquake, and show that they can cause further earthquakes at any distance if their amplitude exceeds several microstrain, regardless of their frequency content. These triggering requirements are remarkably similar to those measured in the laboratory for inducing dynamic elastic nonlinear behaviour, which suggests that the underlying physics is similar. 相似文献
127.
Porco CC Baker E Barbara J Beurle K Brahic A Burns JA Charnoz S Cooper N Dawson DD Del Genio AD Denk T Dones L Dyudina U Evans MW Fussner S Giese B Grazier K Helfenstein P Ingersoll AP Jacobson RA Johnson TV McEwen A Murray CD Neukum G Owen WM Perry J Roatsch T Spitale J Squyres S Thomas P Tiscareno M Turtle EP Vasavada AR Veverka J Wagner R West R 《Nature》2005,434(7030):159-168
Titan, the largest moon of Saturn, is the only satellite in the Solar System with a substantial atmosphere. The atmosphere is poorly understood and obscures the surface, leading to intense speculation about Titan's nature. Here we present observations of Titan from the imaging science experiment onboard the Cassini spacecraft that address some of these issues. The images reveal intricate surface albedo features that suggest aeolian, tectonic and fluvial processes; they also show a few circular features that could be impact structures. These observations imply that substantial surface modification has occurred over Titan's history. We have not directly detected liquids on the surface to date. Convective clouds are found to be common near the south pole, and the motion of mid-latitude clouds consistently indicates eastward winds, from which we infer that the troposphere is rotating faster than the surface. A detached haze at an altitude of 500 km is 150-200 km higher than that observed by Voyager, and more tenuous haze layers are also resolved. 相似文献
128.
Farmer H McCabe N Lord CJ Tutt AN Johnson DA Richardson TB Santarosa M Dillon KJ Hickson I Knights C Martin NM Jackson SP Smith GC Ashworth A 《Nature》2005,434(7035):917-921
BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer. 相似文献
129.
130.
Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity 总被引:1,自引:0,他引:1
Harvey NL Srinivasan RS Dillard ME Johnson NC Witte MH Boyd K Sleeman MW Oliver G 《Nature genetics》2005,37(10):1072-1081
Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease. 相似文献