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41.
The only naturally occurring isotope of bismuth, 209Bi, is commonly regarded as the heaviest stable isotope. But like most other heavy nuclei abundant in nature and characterized by an exceptionally long lifetime, it is metastable with respect to alpha-decay. However, the decay usually evades observation because the nuclear structure of 209Bi gives rise to an extremely low decay probability and, moreover, generates low-energy alpha-particles difficult to detect. Indeed, dedicated experiments attempting to record the alpha-decay of 209Bi in nuclear emulsions failed. However, scintillating bolometers operated at temperatures below 100 mK offer improved detection efficiency and sensitivity, whereas a broad palette of targets could be available. Here we report the successful use of this method for the unambiguous detection of 209Bi alpha-decay in bismuth germanate detectors cooled to 20 mK. We measure an energy release of 3,137 +/- 1 (statistical) +/- 2 (systematic) keV and a half-life of (1.9 +/- 0.2) x 10(19) yr, which are in agreement with expected values. 相似文献
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Bocquet N Prado de Carvalho L Cartaud J Neyton J Le Poupon C Taly A Grutter T Changeux JP Corringer PJ 《Nature》2007,445(7123):116-119
Ligand-gated ion channels (LGICs) mediate excitatory and inhibitory transmission in the nervous system. Among them, the pentameric or 'Cys-loop' receptors (pLGICs) compose a family that until recently was found in only eukaryotes. Yet a recent genome search identified putative homologues of these proteins in several bacterial species. Here we report the cloning, expression and functional identification of one of these putative homologues from the cyanobacterium Gloeobacter violaceus. It was expressed as a homo-oligomer in HEK 293 cells and Xenopus oocytes, generating a transmembrane cationic channel that is opened by extracellular protons and shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Electron microscopy and cross-linking experiments of the protein fused to the maltose-binding protein and expressed in Escherichia coli are consistent with a homo-pentameric organization. Sequence comparison shows that it possesses a compact structure, with the absence of the amino-terminal helix, the canonical disulphide bridge and the large cytoplasmic domain found in eukaryotic pLGICs. Therefore it embodies a minimal structure required for signal transduction. These data establish the prokaryotic origin of the family. Because Gloeobacter violaceus carries out photosynthesis and proton transport at the cytoplasmic membrane, this new proton-gated ion channel might contribute to adaptation to pH change. 相似文献
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Challen GA Sun D Jeong M Luo M Jelinek J Berg JS Bock C Vasanthakumar A Gu H Xi Y Liang S Lu Y Darlington GJ Meissner A Issa JP Godley LA Li W Goodell MA 《Nature genetics》2012,44(1):23-31
Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a loss progressively impairs hematopoietic stem cell (HSC) differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs show both increased and decreased methylation at distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null HSCs upregulate HSC multipotency genes and downregulate differentiation factors, and their progeny exhibit global hypomethylation and incomplete repression of HSC-specific genes. These data establish Dnmt3a as a critical participant in the epigenetic silencing of HSC regulatory genes, thereby enabling efficient differentiation. 相似文献
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Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome. Considering that 99% of cancer-specific mutations are located in those allegedly non-coding regions, cryptic MAPs could furthermore represent a particularly rich source of tumor-specific antigens. However, extensive proteogenomic analyses will be required to determine the breath as well as the temporal and spatial plasticity of the cryptic MAP repertoire in normal and neoplastic cells. 相似文献
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The fungal glutathione S-transferase system. Evidence of new classes in the wood-degrading basidiomycete Phanerochaete chrysosporium 总被引:1,自引:0,他引:1
Mélanie Morel Andrew A. Ngadin Michel Droux Jean-Pierre Jacquot Eric Gelhaye 《Cellular and molecular life sciences : CMLS》2009,66(23):3711-3725
The recent release of several basidiomycete genome sequences allows an improvement of the classification of fungal glutathione S-transferases (GSTs). GSTs are well-known detoxification enzymes which can catalyze the conjugation of glutathione to non-polar compounds that contain an electrophilic carbon, nitrogen, or sulfur atom. Following this mechanism, they are able to metabolize drugs, pesticides, and many other xenobiotics and peroxides. A genomic and phylogenetic analysis of GST classes in various sequenced fungi—zygomycetes, ascomycetes, and basidiomycetes—revealed some particularities in GST distribution, in comparison with previous analyses with ascomycetes only. By focusing essentially on the wood-degrading basidiomycete Phanerochaete chrysosporium, this analysis highlighted a new fungal GST class named GTE, which is related to bacterial etherases, and two new subclasses of the omega class GSTs. Moreover, our phylogenetic analysis suggests a relationship between the saprophytic behavior of some fungi and the number and distribution of some GST isoforms within specific classes. 相似文献
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Diehl R Halloin H Kretschmer K Lichti GG Schönfelder V Strong AW von Kienlin A Wang W Jean P Knödlseder J Roques JP Weidenspointner G Schanne S Hartmann DH Winkler C Wunderer C 《Nature》2006,439(7072):45-47
Gamma-rays from radioactive 26Al (half-life approximately 7.2 x 10(5) years) provide a 'snapshot' view of continuing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along its plane. This led to the conclusion that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show evidence for locally produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/- 0.8) solar masses of 26Al. We use this to determine that the frequency of core collapse (that is, type Ib/c and type II) supernovae is 1.9 (+/- 1.1) events per century. 相似文献
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Lebreton JP Witasse O Sollazzo C Blancquaert T Couzin P Schipper AM Jones JB Matson DL Gurvits LI Atkinson DH Kazeminejad B Pérez-Ayúcar M 《Nature》2005,438(7069):758-764
Titan, Saturn's largest moon, is the only Solar System planetary body other than Earth with a thick nitrogen atmosphere. The Voyager spacecraft confirmed that methane was the second-most abundant atmospheric constituent in Titan's atmosphere, and revealed a rich organic chemistry, but its cameras could not see through the thick organic haze. After a seven-year interplanetary journey on board the Cassini orbiter, the Huygens probe was released on 25 December 2004. It reached the upper layer of Titan's atmosphere on 14 January and landed softly after a parachute descent of almost 2.5 hours. Here we report an overview of the Huygens mission, which enabled studies of the atmosphere and surface, including in situ sampling of the organic chemistry, and revealed an Earth-like landscape. The probe descended over the boundary between a bright icy terrain eroded by fluvial activity--probably due to methane-and a darker area that looked like a river- or lake-bed. Post-landing images showed centimetre-sized surface details. 相似文献
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The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum 总被引:4,自引:0,他引:4
Howard HC Mount DB Rochefort D Byun N Dupré N Lu J Fan X Song L Rivière JB Prévost C Horst J Simonati A Lemcke B Welch R England R Zhan FQ Mercado A Siesser WB George AL McDonald MP Bouchard JP Mathieu J Delpire E Rouleau GA 《Nature genetics》2002,32(3):384-392
Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. ACCPN is transmitted in an autosomal recessive fashion and is found at a high frequency in the province of Quebec, Canada. ACCPN has been previously mapped to chromosome 15q. The gene SLC12A6 (solute carrier family 12, member 6), which encodes the K+-Cl- transporter KCC3 and maps within the ACCPN candidate region, was screened for mutations in individuals with ACCPN. Four distinct protein-truncating mutations were found: two in the French Canadian population and two in non-French Canadian families. The functional consequence of the predominant French Canadian mutation (2436delG, Thr813fsX813) was examined by heterologous expression of wildtype and mutant KCC3 in Xenopus laevis oocytes; the truncated mutant is appropriately glycosylated and expressed at the cellular membrane, where it is non-functional. Mice generated with a targeted deletion of Slc12a6 have a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit, similar to the human disease. Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system. 相似文献
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Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases 总被引:1,自引:0,他引:1
Redondo P Prieto J Muñoz IG Alibés A Stricher F Serrano L Cabaniols JP Daboussi F Arnould S Perez C Duchateau P Pâques F Blanco FJ Montoya G 《Nature》2008,456(7218):107-111
Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases-such as homing endonucleases, also known as meganucleases-constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double-strand-break-induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I-CreI, produced by a semi-rational approach. These two molecules-Amel3-Amel4 and Ini3-Ini4-cleave DNA from the human XPC gene (xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I-CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild-type I-CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo. 相似文献