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261.
262.
Kaneko H Dridi S Tarallo V Gelfand BD Fowler BJ Cho WG Kleinman ME Ponicsan SL Hauswirth WW Chiodo VA Karikó K Yoo JW Lee DK Hadziahmetovic M Song Y Misra S Chaudhuri G Buaas FW Braun RE Hinton DR Zhang Q Grossniklaus HE Provis JM Madigan MC Milam AH Justice NL Albuquerque RJ Blandford AD Bogdanovich S Hirano Y Witta J Fuchs E Littman DR Ambati BK Rudin CM Chong MM Provost P Kugel JF Goodrich JA Dunaief JL Baffi JZ Ambati J 《Nature》2011,471(7338):325-330
263.
Quantum decoherence is a central concept in physics. Applications such as quantum information processing depend on understanding it; there are even fundamental theories proposed that go beyond quantum mechanics, in which the breakdown of quantum theory would appear as an 'intrinsic' decoherence, mimicking the more familiar environmental decoherence processes. Such applications cannot be optimized, and such theories cannot be tested, until we have a firm handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate and testable predictions for environmental decoherence in molecular-based quantum magnets. Experiments on molecular magnets have successfully demonstrated quantum-coherent phenomena but the decoherence processes that ultimately limit such behaviour were not well constrained. For molecular magnets, theory predicts three principal contributions to environmental decoherence: from phonons, from nuclear spins and from intermolecular dipolar interactions. We use high magnetic fields on single crystals of Fe(8) molecular magnets (in which the Fe ions are surrounded by organic ligands) to suppress dipolar and nuclear-spin decoherence. In these high-field experiments, we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally, and there are no other visible decoherence sources. In these high fields, we obtain a maximum decoherence quality-factor of 1.49?×?10(6); our investigation suggests that the environmental decoherence time can be extended up to about 500 microseconds, with a decoherence quality factor of ~6?×?10(7), by optimizing the temperature, magnetic field and nuclear isotopic concentrations. 相似文献
264.
Rasmussen SG DeVree BT Zou Y Kruse AC Chung KY Kobilka TS Thian FS Chae PS Pardon E Calinski D Mathiesen JM Shah ST Lyons JA Caffrey M Gellman SH Steyaert J Skiniotis G Weis WI Sunahara RK Kobilka BK 《Nature》2011,477(7366):549-555
G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR. 相似文献
265.
Primitive agriculture in a social amoeba 总被引:1,自引:0,他引:1
Agriculture has been a large part of the ecological success of humans. A handful of animals, notably the fungus-growing ants, termites and ambrosia beetles, have advanced agriculture that involves dispersal and seeding of food propagules, cultivation of the crop and sustainable harvesting. More primitive examples, which could be called husbandry because they involve fewer adaptations, include marine snails farming intertidal fungi and damselfish farming algae. Recent work has shown that microorganisms are surprisingly like animals in having sophisticated behaviours such as cooperation, communication and recognition, as well as many kinds of symbiosis. Here we show that the social amoeba Dictyostelium discoideum has a primitive farming symbiosis that includes dispersal and prudent harvesting of the crop. About one-third of wild-collected clones engage in husbandry of bacteria. Instead of consuming all bacteria in their patch, they stop feeding early and incorporate bacteria into their fruiting bodies. They then carry bacteria during spore dispersal and can seed a new food crop, which is a major advantage if edible bacteria are lacking at the new site. However, if they arrive at sites already containing appropriate bacteria, the costs of early feeding cessation are not compensated for, which may account for the dichotomous nature of this farming symbiosis. The striking convergent evolution between bacterial husbandry in social amoebas and fungus farming in social insects makes sense because multigenerational benefits of farming go to already established kin groups. 相似文献
266.
Facciabene A Peng X Hagemann IS Balint K Barchetti A Wang LP Gimotty PA Gilks CB Lal P Zhang L Coukos G 《Nature》2011,475(7355):226-230
Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth. 相似文献
267.
268.
Until recently, intricate details of the optical design of non-biomineralized arthropod eyes remained elusive in Cambrian Burgess-Shale-type deposits, despite exceptional preservation of soft-part anatomy in such Konservat-Lagerst?tten. The structure and development of ommatidia in arthropod compound eyes support a single origin some time before the latest common ancestor of crown-group arthropods, but the appearance of compound eyes in the arthropod stem group has been poorly constrained in the absence of adequate fossils. Here we report 2-3-cm paired eyes from the early Cambrian (approximately 515 million years old) Emu Bay Shale of South Australia, assigned to the Cambrian apex predator Anomalocaris. Their preserved visual surfaces are composed of at least 16,000 hexagonally packed ommatidial lenses (in a single eye), rivalling the most acute compound eyes in modern arthropods. The specimens show two distinct taphonomic modes, preserved as iron oxide (after pyrite) and calcium phosphate, demonstrating that disparate styles of early diagenetic mineralization can replicate the same type of extracellular tissue (that is, cuticle) within a single Burgess-Shale-type deposit. These fossils also provide compelling evidence for the arthropod affinities of anomalocaridids, push the origin of compound eyes deeper down the arthropod stem lineage, and indicate that the compound eye evolved before such features as a hardened exoskeleton. The inferred acuity of the anomalocaridid eye is consistent with other evidence that these animals were highly mobile visual predators in the water column. The existence of large, macrophagous nektonic predators possessing sharp vision--such as Anomalocaris--within the early Cambrian ecosystem probably helped to accelerate the escalatory 'arms race' that began over half a billion years ago. 相似文献
269.
Heritable variation in behavioural traits generally has a complex genetic basis, and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species and provided insights into its diverse microbial ecology. C. elegans responds to bacterial infection with conserved innate immune responses and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens. 相似文献
270.
Wertz IE Kusam S Lam C Okamoto T Sandoval W Anderson DJ Helgason E Ernst JA Eby M Liu J Belmont LD Kaminker JS O'Rourke KM Pujara K Kohli PB Johnson AR Chiu ML Lill JR Jackson PK Fairbrother WJ Seshagiri S Ludlam MJ Leong KG Dueber EC Maecker H Huang DC Dixit VM 《Nature》2011,471(7336):110-114
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics. 相似文献