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51.
Prüfer K Munch K Hellmann I Akagi K Miller JR Walenz B Koren S Sutton G Kodira C Winer R Knight JR Mullikin JC Meader SJ Ponting CP Lunter G Higashino S Hobolth A Dutheil J Karakoç E Alkan C Sajjadian S Catacchio CR Ventura M Marques-Bonet T Eichler EE André C Atencia R Mugisha L Junhold J Patterson N Siebauer M Good JM Fischer A Ptak SE Lachmann M Symer DE Mailund T Schierup MH Andrés AM Kelso J Pääbo S 《Nature》2012,486(7404):527-531
Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. 相似文献
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Ngo VN Young RM Schmitz R Jhavar S Xiao W Lim KH Kohlhammer H Xu W Yang Y Zhao H Shaffer AL Romesser P Wright G Powell J Rosenwald A Muller-Hermelink HK Ott G Gascoyne RD Connors JM Rimsza LM Campo E Jaffe ES Delabie J Smeland EB Fisher RI Braziel RM Tubbs RR Cook JR Weisenburger DD Chan WC Staudt LM 《Nature》2011,470(7332):115-119
The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations. 相似文献
54.
夏季黄连木排放萜烯类化合物浓度日变化及排放速率的研究 总被引:1,自引:0,他引:1
采用流动式采样与气相色谱 质谱联用法研究了意大利撒丁岛Noak’sArk自然生态区主要灌木黄连木 (Pistacialentiscus)萜烯类化合物排放特征、排放速率及其日变化。排放物种包括α 蒎烯、β 蒎烯、桧烯、苎烯、戊花烃、莰烯、β 水芹烯、β 香叶烯、α 松油烯、α 水芹烯和 3 蒈烯 ,以及少量异戊二烯。萜烯类化合物占总排放的 99 4%,异戊二烯仅占 0 6%。在萜烯类化合物中 ,主要排放物为α 蒎烯、β 蒎烯、桧烯和苎烯 ,分别占总排放的 64 5 %、18 4%、6 0 %和 5 9%。萜烯排放速率随温度的升高而增加 ,呈指数相关。在标准条件下 ( 30 3K) ,黄连木树种的排放速率为 2 72±0 72 μg g·h。黄连木排放速率公式中 β值为 0 12 8K-1,与文献值 0 0 5 7~ 0 144K-1相一致。 相似文献
55.
Christina Ulm Mona Saffarzadeh Poornima Mahavadi Sandra Müller Gerlinde Prem Farhan Saboor Peter Simon Ralf Middendorff Hildegard Geyer Ingrid Henneke Nils Bayer Susanne Rinné Thomas Lütteke Eva Böttcher-Friebertshäuser Rita Gerardy-Schahn David Schwarzer Martina Mühlenhoff Klaus T. Preissner Andreas Günther Rudolf Geyer Sebastian P. Galuska 《Cellular and molecular life sciences : CMLS》2013,70(19):3695-3708
Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes. 相似文献
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57.
Summary A presumably new species of pathogenic treponemes was isolated from a lesion on the male organs of hare (Lepus sp.) and the scrotum of a rabbit (Oryctolagus sp.) was infected with this treponeme. Lesion developed on the scrotum after a 110-day incubation. 相似文献
58.
Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies 总被引:24,自引:0,他引:24
Michele DE Barresi R Kanagawa M Saito F Cohn RD Satz JS Dollar J Nishino I Kelley RI Somer H Straub V Mathews KD Moore SA Campbell KP 《Nature》2002,418(6896):417-422
Muscle eye brain disease (MEB) and Fukuyama congenital muscular dystrophy (FCMD) are congenital muscular dystrophies with associated, similar brain malformations. The FCMD gene, fukutin, shares some homology with fringe-like glycosyltransferases, and the MEB gene, POMGnT1, seems to be a new glycosyltransferase. Here we show, in both MEB and FCMD patients, that alpha-dystroglycan is expressed at the muscle membrane, but similar hypoglycosylation in the diseases directly abolishes binding activity of dystroglycan for the ligands laminin, neurexin and agrin. We show that this post-translational biochemical and functional disruption of alpha-dystroglycan is recapitulated in the muscle and central nervous system of mutant myodystrophy (myd) mice. We demonstrate that myd mice have abnormal neuronal migration in cerebral cortex, cerebellum and hippocampus, and show disruption of the basal lamina. In addition, myd mice reveal that dystroglycan targets proteins to functional sites in brain through its interactions with extracellular matrix proteins. These results suggest that at least three distinct mammalian genes function within a convergent post-translational processing pathway during the biosynthesis of dystroglycan, and that abnormal dystroglycan-ligand interactions underlie the pathogenic mechanism of muscular dystrophy with brain abnormalities. 相似文献
59.
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus 总被引:53,自引:0,他引:53
Cowley MA Smart JL Rubinstein M Cerdán MG Diano S Horvath TL Cone RD Low MJ 《Nature》2001,411(6836):480-484
The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (gamma-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus. 相似文献
60.
A presumably new species of pathogenic treponemes was isolated from a lesion on the male organs of hare (Lepus sp.) and the scrotum of a rabbit (Oryctolagus sp.) was infected with this treponeme. Lesion developed on the scrotum after a 110-day incubation. 相似文献