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81.
A microRNA polycistron as a potential human oncogene 总被引:5,自引:0,他引:5
He L Thomson JM Hemann MT Hernando-Monge E Mu D Goodson S Powers S Cordon-Cardo C Lowe SW Hannon GJ Hammond SM 《Nature》2005,435(7043):828-833
To date, more than 200 microRNAs have been described in humans; however, the precise functions of these regulatory, non-coding RNAs remains largely obscure. One cluster of microRNAs, the mir-17-92 polycistron, is located in a region of DNA that is amplified in human B-cell lymphomas. Here we compared B-cell lymphoma samples and cell lines to normal tissues, and found that the levels of the primary or mature microRNAs derived from the mir-17-92 locus are often substantially increased in these cancers. Enforced expression of the mir-17-92 cluster acted with c-myc expression to accelerate tumour development in a mouse B-cell lymphoma model. Tumours derived from haematopoietic stem cells expressing a subset of the mir-17-92 cluster and c-myc could be distinguished by an absence of apoptosis that was otherwise prevalent in c-myc-induced lymphomas. Together, these studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate the mir-17-92 cluster as a potential human oncogene. 相似文献
82.
Hillier LW Graves TA Fulton RS Fulton LA Pepin KH Minx P Wagner-McPherson C Layman D Wylie K Sekhon M Becker MC Fewell GA Delehaunty KD Miner TL Nash WE Kremitzki C Oddy L Du H Sun H Bradshaw-Cordum H Ali J Carter J Cordes M Harris A Isak A van Brunt A Nguyen C Du F Courtney L Kalicki J Ozersky P Abbott S Armstrong J Belter EA Caruso L Cedroni M Cotton M Davidson T Desai A Elliott G Erb T Fronick C Gaige T Haakenson W Haglund K Holmes A Harkins R Kim K Kruchowski SS Strong CM Grewal N Goyea E 《Nature》2005,434(7034):724-731
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions. 相似文献
83.
Numerous non-mammalian vertebrates have evolved lethal venoms to aid either in securing prey or as protection from predators, but modern mammals that use venoms in these ways are rare, including only the duck-billed platypus (Ornithorhynchus), the Caribbean Solenodon, and a few shrews (Soricidae) (Order Insectivora). Here we report evidence of a venom delivery apparatus in extinct mammals, documented by well-preserved specimens recovered from late Palaeocene rocks in Alberta, Canada. Although classified within Eutheria, these mammals are phylogenetically remote from modern Insectivora and have evolved specialized teeth as salivary venom delivery systems (VDSs) that differ markedly from one another and from those of Solenodon and shrews. Our discoveries therefore show that mammals have been much more flexible in the evolution of VDSs than previously believed, contradicting currently held notions that modern insectivorans are representative of the supposedly limited role of salivary venoms in mammalian history. Evidently, small predatory eutherians have paralleled colubroid snakes in evolving salivary venoms and their delivery systems several times independently. 相似文献
84.
Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP 总被引:1,自引:0,他引:1
Bricelj VM Connell L Konoki K Macquarrie SP Scheuer T Catterall WA Trainer VL 《Nature》2005,434(7034):763-767
Bivalve molluscs, the primary vectors of paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their capacity to accumulate PSP toxins (PSTs) which has a neural basis. PSTs cause human fatalities by blocking sodium conductance in nerve fibres. Here we identify a molecular basis for inter-population variation in PSP resistance within a species, consistent with genetic adaptation to PSTs. Softshell clams (Mya arenaria) from areas exposed to 'red tides' are more resistant to PSTs, as demonstrated by whole-nerve assays, and accumulate toxins at greater rates than sensitive clams from unexposed areas. PSTs lead to selective mortality of sensitive clams. Resistance is caused by natural mutation of a single amino acid residue, which causes a 1,000-fold decrease in affinity at the saxitoxin-binding site in the sodium channel pore of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans. Furthermore, global expansion of PSP to previously unaffected coastal areas might result in long-term changes to communities and ecosystems. 相似文献
85.
The large ribosomal subunit catalyses the reaction between the alpha-amino group of the aminoacyl-tRNA bound to the A site and the ester carbon of the peptidyl-tRNA bound to the P site, while preventing the nucleophilic attack of water on the ester, which would lead to unprogrammed deacylation of the peptidyl-tRNA. Here we describe three new structures of the large ribosomal subunit of Haloarcula marismortui (Hma) complexed with peptidyl transferase substrate analogues that reveal an induced-fit mechanism in which substrates and active-site residues reposition to allow the peptidyl transferase reaction. Proper binding of an aminoacyl-tRNA analogue to the A site induces specific movements of 23S rRNA nucleotides 2618-2620 (Escherichia coli numbering 2583-2585) and 2541(2506), thereby reorienting the ester group of the peptidyl-tRNA and making it accessible for attack. In the absence of the appropriate A-site substrate, the peptidyl transferase centre positions the ester link of the peptidyl-tRNA in a conformation that precludes the catalysed nucleophilic attack by water. Protein release factors may also function, in part, by inducing an active-site rearrangement similar to that produced by the A-site aminoacyl-tRNA, allowing the carbonyl group and water to be positioned for hydrolysis. 相似文献
86.
87.
Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms 总被引:15,自引:0,他引:15
Orr JC Fabry VJ Aumont O Bopp L Doney SC Feely RA Gnanadesikan A Gruber N Ishida A Joos F Key RM Lindsay K Maier-Reimer E Matear R Monfray P Mouchet A Najjar RG Plattner GK Rodgers KB Sabine CL Sarmiento JL Schlitzer R Slater RD Totterdell IJ Weirig MF Yamanaka Y Yool A 《Nature》2005,437(7059):681-686
Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously. 相似文献
88.
Hereditary deficiency of pseudocholinesterase in Eskimos 总被引:6,自引:0,他引:6
89.
Stable messenger RNA in nucleated erythrocytes 总被引:1,自引:0,他引:1
90.
C. A. Baile F. Anne Scott J. Mayer 《Cellular and molecular life sciences : CMLS》1967,23(12):1033-1034
Résumé Par des lésions bilatérales hypothalamiques on a rendu des rats aphagiques et adipsiques. Durant la période de convalescence, on a injecté dans le ventricule latéral du pentotal de sodium (ce qui normalement fait manger les animaux) et une solution saline hypertonique (qui normalement les fait boire). On a trouvé qu'après les lésions les rats ne réagissent que lorsqu'ils sont redevenus capables de manger et de boire spontanément.
This work was supported in part by a grant from the National Institute of Neurological Diseases and Blindness, No. NB 01941, of the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland; by a grant from the National Science Foundation, No. GB-4594, Washington, D.C.; and the Fund for Research and Teaching of the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. 相似文献
This work was supported in part by a grant from the National Institute of Neurological Diseases and Blindness, No. NB 01941, of the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland; by a grant from the National Science Foundation, No. GB-4594, Washington, D.C.; and the Fund for Research and Teaching of the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. 相似文献