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41.
Kulkarni SR Ofek EO Rau A Cenko SB Soderberg AM Fox DB Gal-Yam A Capak PL Moon DS Li W Filippenko AV Egami E Kartaltepe J Sanders DB 《Nature》2007,447(7143):458-460
Historically, variable and transient sources have both surprised astronomers and provided new views of the heavens. Here we report the discovery of an optical transient in the outskirts of the lenticular galaxy Messier 85 in the Virgo cluster. With a peak absolute R magnitude of -12, this event is distinctly brighter than novae, but fainter than type Ia supernovae (which are expected in a population of old stars in lenticular galaxies). Archival images of the field do not show a luminous star at that position with an upper limit in the g filter of about -4.1 mag, so it is unlikely to be a giant eruption from a luminous blue variable star. Over a two-month period, the transient source emitted radiation energy of almost 10(47) erg and subsequently faded in the optical sky. It is similar to, but six times more luminous at peak than, an enigmatic transient in the galaxy M31 (ref. 1). A possible origin of M85 OT2006-1 is a stellar merger. If so, searches for similar events in nearby galaxies will not only allow study of the physics of hyper-Eddington sources, but also probe an important phase in the evolution of stellar binary systems. 相似文献
42.
O'Donovan MC Craddock N Norton N Williams H Peirce T Moskvina V Nikolov I Hamshere M Carroll L Georgieva L Dwyer S Holmans P Marchini JL Spencer CC Howie B Leung HT Hartmann AM Möller HJ Morris DW Shi Y Feng G Hoffmann P Propping P Vasilescu C Maier W Rietschel M Zammit S Schumacher J Quinn EM Schulze TG Williams NM Giegling I Iwata N Ikeda M Darvasi A Shifman S He L Duan J Sanders AR Levinson DF Gejman PV Cichon S Nöthen MM Gill M Corvin A Rujescu D Kirov G Owen MJ Buccola NG Mowry BJ 《Nature genetics》2008,40(9):1053-1055
We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)). 相似文献
43.
γ-Secretase is a promiscuous protease that cleaves bitopic membrane proteins within the lipid bilayer. Elucidating both the
mechanistic basis of γ-secretase proteolysis and the precise factors regulating substrate identification is important because
modulation of this biochemical degradative process can have important consequences in a physiological and pathophysiological
context. Here, we briefly review such information for all major classes of intramembranously cleaving proteases (I-CLiPs),
with an emphasis on γ-secretase, an I-CLiP closely linked to the etiology of Alzheimer’s disease. A large body of emerging
data allows us to survey the substrates of γ-secretase to ascertain the conformational features that predispose a peptide
to cleavage by this enigmatic protease. Because substrate specificity in vivo is closely linked to the relative subcellular compartmentalization of γ-secretase and its substrates, we also survey the
voluminous body of literature concerning the traffic of γ-secretase and its most prominent substrate, the amyloid precursor
protein.
Received 4 October 2007; received after revision 1 December 2007; accepted 7 December 2007 相似文献
44.
Hunt KA Zhernakova A Turner G Heap GA Franke L Bruinenberg M Romanos J Dinesen LC Ryan AW Panesar D Gwilliam R Takeuchi F McLaren WM Holmes GK Howdle PD Walters JR Sanders DS Playford RJ Trynka G Mulder CJ Mearin ML Verbeek WH Trimble V Stevens FM O'Morain C Kennedy NP Kelleher D Pennington DJ Strachan DP McArdle WL Mein CA Wapenaar MC Deloukas P McGinnis R McManus R Wijmenga C van Heel DA 《Nature genetics》2008,40(4):395-402
Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. 相似文献
45.
P.M. Sanders 《Annals of science》2013,70(6):513-566
The mathematical works of the French philosopher Charles de Bovelles (c. 1479–1566) have received little attention from historians of scientific thought. At the University of Paris, Bovelles studied under Jacques Lefèvre d'Étaples, sharing with him a high regard for the Christian Neoplatonic philosophy of Nicholas of Cusa. One aspect of Cusanus's philosophy (described in his major work, On Learned Ignorance) was particularly favoured by Lefèvre and Bovelles: the use of geometrical symbolism to provide mathematical guidance to the divine. While Lefèvre was preparing an edition of Cusanus's works (Paris, 1514), Bovelles wrote a treatise of his own, in which the geometry of the five polyhedra was used to provide an approach to the mystery of the Trinity. Seen in the context of Renaissance syncretism of Platonism and Christianity, Bovelles's treatise adds a theological layer of interpretation to the literal meaning of the polyhedral physics described by Plato in the Timaeus. In so doing, it contributes to the discussion of a problem that was later to concern several Renaissance philosophers and cosmologists, including, at the end of the century, Johannes Kepler. 相似文献
46.
Victor Tapias Xiaoping Hu Kelvin C. Luk Laurie H. Sanders Virginia M. Lee J. Timothy Greenamyre 《Cellular and molecular life sciences : CMLS》2017,74(15):2851-2874
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson’s disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons. A time- and dose-dependent accumulation of α-syn was observed following PFFs exposure that also underwent phosphorylation at serine 129. PFFs treatment decreased the expression levels of synaptic proteins, caused alterations in axonal transport-related proteins, and increased H2AX Ser139 phosphorylation. Mitochondrial impairment (including modulation of mitochondrial dynamics-associated protein content), enhanced oxidative stress, and an inflammatory response were also detected in our experimental paradigm. In attempt to unravel a potential molecular mechanism of PFFs neurotoxicity, the expression of inducible nitric oxide synthase was blocked; a significant decline in protein nitration levels and protection against PFFs-induced DA neuron death were observed. Combined exposure to PFFs and rotenone resulted in an additive toxicity. Strikingly, many of the harmful effects found were more prominent in DA rather than non-DA neurons, suggestive of higher susceptibility to degenerate. These findings provide new insights into the role of α-syn in the pathogenesis of PD and could represent a novel and valuable model to study DA-related neurodegeneration. 相似文献
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Low gene copy number shows that arbuscular mycorrhizal fungi inherit genetically different nuclei 总被引:1,自引:0,他引:1
Arbuscular mycorrhizal fungi (AMF) are ancient asexually reproducing organisms that form symbioses with the majority of plant species, improving plant nutrition and promoting plant diversity. Little is known about the evolution or organization of the genomes of any eukaryotic symbiont or ancient asexual organism. Direct evidence shows that one AMF species is heterokaryotic; that is, containing populations of genetically different nuclei. It has been suggested, however, that the genetic variation passed from generation to generation in AMF is simply due to multiple chromosome sets (that is, high ploidy). Here we show that previously documented genetic variation in Pol-like sequences, which are passed from generation to generation, cannot be due to either high ploidy or repeated gene duplications. Our results provide the clearest evidence so far for substantial genetic differences among nuclei in AMF. We also show that even AMF with a very large nuclear DNA content are haploid. An underlying principle of evolutionary theory is that an individual passes on one or half of its genome to each of its progeny. The coexistence of a population of many genomes in AMF and their transfer to subsequent generations, therefore, has far-reaching consequences for understanding genome evolution. 相似文献