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1.
Jonker JW Suh JM Atkins AR Ahmadian M Li P Whyte J He M Juguilon H Yin YQ Phillips CT Yu RT Olefsky JM Henry RR Downes M Evans RM 《Nature》2012,485(7398):391-394
Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization. 相似文献
2.
Soil fertility limits carbon sequestration by forest ecosystems in a CO2-enriched atmosphere 总被引:15,自引:0,他引:15
Oren R Ellsworth DS Johnsen KH Phillips N Ewers BE Maier C Schäfer KV McCarthy H Hendrey G McNulty SG Katul GG 《Nature》2001,411(6836):469-472
Northern mid-latitude forests are a large terrestrial carbon sink. Ignoring nutrient limitations, large increases in carbon sequestration from carbon dioxide (CO2) fertilization are expected in these forests. Yet, forests are usually relegated to sites of moderate to poor fertility, where tree growth is often limited by nutrient supply, in particular nitrogen. Here we present evidence that estimates of increases in carbon sequestration of forests, which is expected to partially compensate for increasing CO2 in the atmosphere, are unduly optimistic. In two forest experiments on maturing pines exposed to elevated atmospheric CO2, the CO2-induced biomass carbon increment without added nutrients was undetectable at a nutritionally poor site, and the stimulation at a nutritionally moderate site was transient, stabilizing at a marginal gain after three years. However, a large synergistic gain from higher CO2 and nutrients was detected with nutrients added. This gain was even larger at the poor site (threefold higher than the expected additive effect) than at the moderate site (twofold higher). Thus, fertility can restrain the response of wood carbon sequestration to increased atmospheric CO2. Assessment of future carbon sequestration should consider the limitations imposed by soil fertility, as well as interactions with nitrogen deposition. 相似文献
3.
Ultracold atoms trapped by light offer robust quantum coherence and controllability, providing an attractive system for quantum information processing and for the simulation of complex problems in condensed matter physics. Many quantum information processing schemes require the manipulation and deterministic entanglement of individual qubits; this would typically be accomplished using controlled, state-dependent, coherent interactions among qubits. Recent experiments have made progress towards this goal by demonstrating entanglement among an ensemble of atoms confined in an optical lattice. Until now, however, there has been no demonstration of a key operation: controlled entanglement between atoms in isolated pairs. Here we use an optical lattice of double-well potentials to isolate and manipulate arrays of paired (87)Rb atoms, inducing controlled entangling interactions within each pair. Our experiment realizes proposals to use controlled exchange coupling in a system of neutral atoms. Although 87Rb atoms have nearly state-independent interactions, when we force two atoms into the same physical location, the wavefunction exchange symmetry of these identical bosons leads to state-dependent dynamics. We observe repeated interchange of spin between atoms occupying different vibrational levels, with a coherence time of more than ten milliseconds. This observation demonstrates the essential component of a neutral atom quantum SWAP gate (which interchanges the state of two qubits). Its 'half-implementation', the root SWAP gate, is entangling, and together with single-qubit rotations it forms a set of universal gates for quantum computation. 相似文献
4.
Uppal S Diggle CP Carr IM Fishwick CW Ahmed M Ibrahim GH Helliwell PS Latos-Bieleńska A Phillips SE Markham AF Bennett CP Bonthron DT 《Nature genetics》2008,40(6):789-793
Digital clubbing, recognized by Hippocrates in the fifth century BC, is the outward hallmark of pulmonary hypertrophic osteoarthropathy, a clinical constellation that develops secondary to various acquired diseases, especially intrathoracic neoplasm. The pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood, but a clinically indistinguishable primary (idiopathic) form of hypertrophic osteoarthropathy (PHO) is recognized. This familial disorder can cause diagnostic confusion, as well as significant disability. By autozygosity methods, we mapped PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation. Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations. These findings not only suggest therapies for PHO, but also imply that clubbing secondary to other pathologies may be prostaglandin mediated. Testing for HPGD mutations and biochemical testing for HPGD deficiency in patients with unexplained clubbing might help to obviate extensive searches for occult pathology. 相似文献
5.
There is substantial evidence that the martian volatile inventory and climate have changed markedly throughout the planet's history. Clues come from areas as disparate as the history and properties of the deep interior, the composition of the crust and regolith, the morphology of the surface, composition of the present-day atmosphere, and the nature of the interactions between the upper atmosphere and the solar wind. We piece together the relevant observations into a coherent view of the evolution of the martian climate, focusing in particular on the observations that provide the strongest constraints. 相似文献
6.
Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor 总被引:17,自引:0,他引:17
The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures. We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions. 相似文献
7.
Shiva M. Singh Caroline H. Wang Ann Phillips 《Cellular and molecular life sciences : CMLS》1982,38(12):1487-1489
Summary The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).This research was financed by a Natural Sciences and Engineering Research Council Canada grant to S.M.S. 相似文献
8.
9.
Life span of erythrocyte membrane protein 总被引:1,自引:0,他引:1
10.
Detection of human leukaemia associated antigens in leukaemic serum and normal embryos 总被引:4,自引:0,他引:4
R Harris D Viza R Todd J Phillips R Sugar R F Jennison G Marriott M H Gleeson 《Nature》1971,233(5321):556-557