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The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.  相似文献   
416.
The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.  相似文献   
417.
Van Aken BB  Rivera JP  Schmid H  Fiebig M 《Nature》2007,449(7163):702-705
Domains are of unparalleled technological importance as they are used for information storage and for electronic, magnetic and optical switches. They are an essential property of any ferroic material. Three forms of ferroic order are widely known: ferromagnetism, a spontaneous magnetization; ferroelectricity, a spontaneous polarization; and ferroelasticity, a spontaneous strain. It is currently debated whether to include an ordered arrangement of magnetic vortices as a fourth form of ferroic order, termed ferrotoroidicity. Although there are reasons to expect this form of order from the point of view of thermodynamics, a crucial hallmark of the ferroic state--that is, ferrotoroidic domains--has not hitherto been observed. Here ferrotoroidic domains are spatially resolved by optical second harmonic generation in LiCoPO4, where they coexist with independent antiferromagnetic domains. Their space- and time-asymmetric nature relates ferrotoroidics to multiferroics with magnetoelectric phase control and to other systems in which space and time asymmetry leads to possibilities for future applications.  相似文献   
418.
From the standpoints of both basic research and biotechnology, there is considerable interest in reaching a clearer understanding of the diversity of biological mechanisms employed during lignocellulose degradation. Globally, termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. Only recently have data supported any direct role for the symbiotic bacteria in the gut of the termite in cellulose and xylan hydrolysis. Here we use a metagenomic analysis of the bacterial community resident in the hindgut paunch of a wood-feeding 'higher' Nasutitermes species (which do not contain cellulose-fermenting protozoa) to show the presence of a large, diverse set of bacterial genes for cellulose and xylan hydrolysis. Many of these genes were expressed in vivo or had cellulase activity in vitro, and further analyses implicate spirochete and fibrobacter species in gut lignocellulose degradation. New insights into other important symbiotic functions including H2 metabolism, CO2-reductive acetogenesis and N2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-microl environment can be.  相似文献   
419.
The effect of quantum statistics in quantum gases and liquids results in observable collective properties among many-particle systems. One prime example is Bose-Einstein condensation, whose onset in a quantum liquid leads to phenomena such as superfluidity and superconductivity. A Bose-Einstein condensate is generally defined as a macroscopic occupation of a single-particle quantum state, a phenomenon technically referred to as off-diagonal long-range order due to non-vanishing off-diagonal components of the single-particle density matrix. The wavefunction of the condensate is an order parameter whose phase is essential in characterizing the coherence and superfluid phenomena. The long-range spatial coherence leads to the existence of phase-locked multiple condensates in an array of superfluid helium, superconducting Josephson junctions or atomic Bose-Einstein condensates. Under certain circumstances, a quantum phase difference of pi is predicted to develop among weakly coupled Josephson junctions. Such a meta-stable pi-state was discovered in a weak link of superfluid 3He, which is characterized by a 'p-wave' order parameter. The possible existence of such a pi-state in weakly coupled atomic Bose-Einstein condensates has also been proposed, but remains undiscovered. Here we report the observation of spontaneous build-up of in-phase ('zero-state') and antiphase ('pi-state') 'superfluid' states in a solid-state system; an array of exciton-polariton condensates connected by weak periodic potential barriers within a semiconductor microcavity. These in-phase and antiphase states reflect the band structure of the one-dimensional polariton array and the dynamic characteristics of metastable exciton-polariton condensates.  相似文献   
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