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971.
972.
Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia 总被引:3,自引:0,他引:3
Pollock PM Cohen-Solal K Sood R Namkoong J Martino JJ Koganti A Zhu H Robbins C Makalowska I Shin SS Marin Y Roberts KG Yudt LM Chen A Cheng J Incao A Pinkett HW Graham CL Dunn K Crespo-Carbone SM Mackason KR Ryan KB Sinsimer D Goydos J Reuhl KR Eckhaus M Meltzer PS Pavan WJ Trent JM Chen S 《Nature genetics》2003,34(1):108-112
973.
Notch1 functions as a tumor suppressor in mouse skin 总被引:24,自引:0,他引:24
Nicolas M Wolfer A Raj K Kummer JA Mill P van Noort M Hui CC Clevers H Dotto GP Radtke F 《Nature genetics》2003,33(3):416-421
Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin. 相似文献
974.
Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome. 相似文献
975.
Huang E Ishida S Pittman J Dressman H Bild A Kloos M D'Amico M Pestell RG West M Nevins JR 《Nature genetics》2003,34(2):226-230
976.
Stoltze L Rezaei H Jung G Grosclaude J Debey P Schild H Rammensee HG 《Cellular and molecular life sciences : CMLS》2003,60(3):629-638
The prion protein (PrP(C)) is essential for susceptibility to transmissible spongiform encephalopathies. A specific conformer of this protein (PrP(Sc)) is, according to the 'protein only' hypothesis, the principal or only component of the infectious agent, designated prion. Transmission of prions between species is often inefficient, resulting in low attack rates and/or prolonged incubation times and is ascribed to a 'species barrier' caused by differences in the amino acid sequence of PrP between recipient and donor. In this report, we demonstrate that these differences in amino acid sequence result in presentation of distinct peptides on major histocompatibility complex class II molecules. These peptides result in activation of specific CD4+ T cells which leads to the induction of an effective immune response against foreign PrP as demonstrated by antibody production. Therefore, CD4+ T cells represent a crucial component of the immune system to distinguish between foreign and self PrP. 相似文献
977.
978.
Inada N Oguri M Pindor B Hennawi JF Chiu K Zheng W Ichikawa S Gregg MD Becker RH Suto Y Strauss MA Turner EL Keeton CR Annis J Castander FJ Eisenstein DJ Frieman JA Fukugita M Gunn JE Johnston DE Kent SM Nichol RC Richards GT Rix HW Sheldon ES Bahcall NA Brinkmann J Ivezić Z Lamb DQ McKay TA Schneider DP York DG 《Nature》2003,426(6968):810-812
Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model. 相似文献
979.
Burgay M D'Amico N Possenti A Manchester RN Lyne AG Joshi BC McLaughlin MA Kramer M Sarkissian JM Camilo F Kalogera V Kim C Lorimer DR 《Nature》2003,426(6966):531-533
The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe). 相似文献
980.
Price PA Fox DW Kulkarni SR Peterson BA Schmidt BP Soderberg AM Yost SA Berger E Djorgovski SG Frail DA Harrison FA Sari R Blain AW Chapman SC 《Nature》2003,423(6942):844-847
Past studies of cosmological gamma-ray bursts (GRBs) have been hampered by their extreme distances, resulting in faint afterglows. A nearby GRB could potentially shed much light on the origin of these events, but GRBs with a redshift z 相似文献