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101.
The inflammatory reflex   总被引:121,自引:0,他引:121  
Tracey KJ 《Nature》2002,420(6917):853-859
Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.  相似文献   
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103.
Ataxia-telangiectasia is characterized by radiosensitivity, genome instability and predisposition to cancer. Heterozygous carriers of ATM, the gene defective in ataxia-telangiectasia, have a higher than normal risk of developing breast and other cancers. We demonstrate here that Atm 'knock-in' (Atm-Delta SRI) heterozygous mice harboring an in-frame deletion corresponding to the human 7636del9 mutation show an increased susceptibility to developing tumors. In contrast, no tumors are observed in Atm knockout (Atm(+/-)) heterozygous mice. In parallel, we report the appearance of tumors in 6 humans from 12 families who are heterozygous for the 7636del9 mutation. Expression of ATM cDNA containing the 7636del9 mutation had a dominant-negative effect in control cells, inhibiting radiation-induced ATM kinase activity in vivo and in vitro. This reduces the survival of these cells after radiation exposure and enhances the level of radiation-induced chromosomal aberrations. These results show for the first time that mouse carriers of a mutated Atm that are capable of expressing Atm have a higher risk of cancer. This finding provides further support for cancer predisposition in human ataxia-telangiectasia carriers.  相似文献   
104.
Two systemic inquiries, based on soft systems methodology (SSM), into the potential for using community of practice (CoP) theory by an Australian-government created research and development corporation to change its knowledge management (KM) strategy, are reported. Key staff were engaged in the inquiry into how to build a third-order KM strategy based on CoPs; an exploration of key published work on CoPs yielded four SSM activity models—‘being a community practice system’; ‘doing the work of imagination sub-system’; ‘doing the work of alignment sub-system’ and ‘doing the work of engagement sub-system’. These models can be used as heuristics to aid the purposeful design of CoPs in other settings. SSM, enacted as a systemic inquiry, can be understood as a form of systemic action research, which was well equipped to deal with CoP theory and, when enacted participatively, can generate important systemic insights. The inquiry began the process of fostering an appreciation of third order KM but, on the evidence available, did not lead to on-going commitment to a CoPs-based KM strategy. Future research should acknowledge how the framing of research situations influences the research process, the importance of the design of practice change settings and the limited evidence for purposeful interventions leading to successful CoPs.  相似文献   
105.
The leaders of China’s high energy physics sector will soon unveil initial designs for the world’s most technologically advanced circular collider,set to stage near-speed-of-light particle collisions aimed at recreating the conditions of the universe in the instant following the Big Bang.By accelerating beams of leptons or hadrons to nearly300,000 km/s before colliding them inside the ringed  相似文献   
106.
A low mass for Mars from Jupiter's early gas-driven migration   总被引:1,自引:0,他引:1  
Jupiter and Saturn formed in a few million years (ref. 1) from a gas-dominated protoplanetary disk, and were susceptible to gas-driven migration of their orbits on timescales of only ~100,000 years (ref. 2). Hydrodynamic simulations show that these giant planets can undergo a two-stage, inward-then-outward, migration. The terrestrial planets finished accreting much later, and their characteristics, including Mars' small mass, are best reproduced by starting from a planetesimal disk with an outer edge at about one astronomical unit from the Sun (1 au is the Earth-Sun distance). Here we report simulations of the early Solar System that show how the inward migration of Jupiter to 1.5 au, and its subsequent outward migration, lead to a planetesimal disk truncated at 1 au; the terrestrial planets then form from this disk over the next 30-50 million years, with an Earth/Mars mass ratio consistent with observations. Scattering by Jupiter initially empties but then repopulates the asteroid belt, with inner-belt bodies originating between 1 and 3 au and outer-belt bodies originating between and beyond the giant planets. This explains the significant compositional differences across the asteroid belt. The key aspect missing from previous models of terrestrial planet formation is the substantial radial migration of the giant planets, which suggests that their behaviour is more similar to that inferred for extrasolar planets than previously thought.  相似文献   
107.
108.
The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O?≥?1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T?>?2,500?K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.  相似文献   
109.
Intestinal homeostasis and its breakdown in inflammatory bowel disease   总被引:4,自引:0,他引:4  
Maloy KJ  Powrie F 《Nature》2011,474(7351):298-306
Intestinal homeostasis depends on complex interactions between the microbiota, the intestinal epithelium and the host immune system. Diverse regulatory mechanisms cooperate to maintain intestinal homeostasis, and a breakdown in these pathways may precipitate the chronic inflammatory pathology found in inflammatory bowel disease. It is now evident that immune effector modules that drive intestinal inflammation are conserved across innate and adaptive leukocytes and can be controlled by host regulatory cells. Recent evidence suggests that several factors may tip the balance between homeostasis and intestinal inflammation, presenting future challenges for the development of new therapies for inflammatory bowel disease.  相似文献   
110.
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