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Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
385.
Thomas Hawkins 《Archive for History of Exact Sciences》2008,62(6):655-717
The theory of nonnegative matrices is an example of a theory motivated in its origins and development by purely mathematical
concerns that later proved to have a remarkably broad spectrum of applications to such diverse fields as probability theory,
numerical analysis, economics, dynamical programming, and demography. At the heart of the theory is what is usually known
as the Perron–Frobenius Theorem. It was inspired by a theorem of Oskar Perron on positive matrices, usually called Perron’s
Theorem. This paper is primarily concerned with the origins of Perron’s Theorem in his masterful work on ordinary and generalized
continued fractions (1907) and its role in inspiring the remarkable work of Frobenius on nonnegative matrices (1912) that
produced, inter alia, the Perron–Frobenius Theorem. The paper is not at all intended exclusively for readers with expertise
in the theory of nonnegative matrices. Anyone with a basic grounding in linear algebra should be able to read this article
and come away with a good understanding of the Perron–Frobenius Theorem as well as its historical origins. The final section
of the paper considers the first major application of the Perron–Frobenius Theorem, namely, to the theory of Markov chains.
When he introduced the eponymous chains in 1908, Markov adumbrated several key notions and results of the Perron–Frobenius
theory albeit within the much simpler context of stochastic matrices; but it was by means of Frobenius’ 1912 paper that the
linear algebraic foundations of Markov’s theory for nonpositive stochastic matrices were first established by R. Von Mises
and V.I. Romanovsky. 相似文献
386.
Nineteenth-century spiritism was a blend of religious elements, the philosophy of mind, science and popular science and contacts with extraterrestrials were a commonplace phenomenon during spiritistic séances. Using the example of Carl du Prel (1839–1899) I show how his comprehensive mystic philosophy originated in a theory of extraterrestrial life. Carl du Prel used a Darwinian and monistic framework, theories of the unconscious and a Neo-Kantian epistemology to formulate a philosophy of astronomy and extraterrestrial life. He claimed that the mechanism of Darwinian selection is responsible for the distribution of stars and the orbits of the planets. In his speculations on the nature of extraterrestrial life he used the concept of organ projection to argue that technical solutions on earth will be realized organically on other planets and claimed that superior extraterrestrials have quantitatively and qualitatively different senses and thus different forms of intuition. A comparison with Camille Flammarion, spiritist and populariser of astronomy, demonstrates the contextual complexities of spiritism. In contrast to du Prel’s sober Neo-Kantian philosophical speculations, Flammarion was a late proponent of a French esoteric tradition that was rooted in romantic socialism, painted grand cosmological vistas and emphasized reincarnation. I put forward the hypothesis that current discourses on extraterrestrial life are affected by the spiritist tradition mainly through the ‘Golden Age’ science fiction literature of the 1940s and 50s and its successors. However, neither Carl du Prel nor Camille Flammarion contributed significantly to this tradition, which is mainly shaped by the psychical research of J. B. Rhine. 相似文献
387.
S A Taylor R G Snell A Buckler C Ambrose M Duyao D Church C S Lin M Altherr G P Bates N Groot 《Nature genetics》1992,2(3):223-227
We have applied the technique of exon amplification to the isolation of genes from the chromosome 4p16.3 Huntington's disease (HD) candidate region. Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs. The alpha-adducin gene maps immediately telomeric to D4S95, in a region likely to contain the HD defect, and must be scrutinized to establish whether it is the site of the HD mutation. 相似文献
388.
Bonardi V Pesaresi P Becker T Schleiff E Wagner R Pfannschmidt T Jahns P Leister D 《Nature》2005,437(7062):1179-1182
Illumination changes elicit modifications of thylakoid proteins and reorganization of the photosynthetic machinery. This involves, in the short term, phosphorylation of photosystem II (PSII) and light-harvesting (LHCII) proteins. PSII phosphorylation is thought to be relevant for PSII turnover, whereas LHCII phosphorylation is associated with the relocation of LHCII and the redistribution of excitation energy (state transitions) between photosystems. In the long term, imbalances in energy distribution between photosystems are counteracted by adjusting photosystem stoichiometry. In the green alga Chlamydomonas and the plant Arabidopsis, state transitions require the orthologous protein kinases STT7 and STN7, respectively. Here we show that in Arabidopsis a second protein kinase, STN8, is required for the quantitative phosphorylation of PSII core proteins. However, PSII activity under high-intensity light is affected only slightly in stn8 mutants, and D1 turnover is indistinguishable from the wild type, implying that reversible protein phosphorylation is not essential for PSII repair. Acclimation to changes in light quality is defective in stn7 but not in stn8 mutants, indicating that short-term and long-term photosynthetic adaptations are coupled. Therefore the phosphorylation of LHCII, or of an unknown substrate of STN7, is also crucial for the control of photosynthetic gene expression. 相似文献
389.
The spin torque effect that occurs in nanometre-scale magnetic multilayer devices can be used to generate steady-state microwave signals in response to a d.c. electrical current. This establishes a new functionality for magneto-electronic structures that are more commonly used as magnetic field sensors and magnetic memory elements. The microwave power emitted from a single spin torque nano-oscillator (STNO) is at present typically less than 1 nW. To achieve a more useful power level (on the order of microwatts), a device could consist of an array of phase coherent STNOs, in a manner analogous to arrays of Josephson junctions and larger semiconductor oscillators. Here we show that two STNOs in close proximity mutually phase-lock-that is, they synchronize, which is a general tendency of interacting nonlinear oscillator systems. The phase-locked state is distinct, characterized by a sudden narrowing of signal linewidth and an increase in power due to the coherence of the individual oscillators. Arrays of phase-locked STNOs could be used as nanometre-scale reference oscillators. Furthermore, phase control of array elements (phased array) could lead to nanometre-scale directional transmitters and receivers for wireless communications. 相似文献
390.