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141.
Parton LE Ye CP Coppari R Enriori PJ Choi B Zhang CY Xu C Vianna CR Balthasar N Lee CE Elmquist JK Cowley MA Lowell BB 《Nature》2007,449(7159):228-232
A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes. 相似文献
142.
The interactions between plants and their animal pollinators and seed dispersers have moulded much of Earth's biodiversity. Recently, it has been shown that these mutually beneficial interactions form complex networks with a well-defined architecture that may contribute to biodiversity persistence. Little is known, however, about which ecological and evolutionary processes generate these network patterns. Here we use phylogenetic methods to show that the phylogenetic relationships of species predict the number of interactions they exhibit in more than one-third of the networks, and the identity of the species with which they interact in about half of the networks. As a consequence of the phylogenetic effects on interaction patterns, simulated extinction events tend to trigger coextinction cascades of related species. This results in a non-random pruning of the evolutionary tree and a more pronounced loss of taxonomic diversity than expected in the absence of a phylogenetic signal. Our results emphasize how the simultaneous consideration of phylogenetic information and network architecture can contribute to our understanding of the structure and fate of species-rich communities. 相似文献
143.
Milne JC Lambert PD Schenk S Carney DP Smith JJ Gagne DJ Jin L Boss O Perni RB Vu CB Bemis JE Xie R Disch JS Ng PY Nunes JJ Lynch AV Yang H Galonek H Israelian K Choy W Iffland A Lavu S Medvedik O Sinclair DA Olefsky JM Jirousek MR Elliott PJ Westphal CH 《Nature》2007,450(7170):712-716
Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes. 相似文献
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145.
Riebesell U Schulz KG Bellerby RG Botros M Fritsche P Meyerhöfer M Neill C Nondal G Oschlies A Wohlers J Zöllner E 《Nature》2007,450(7169):545-548
The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (CO2) emitted into the atmosphere since pre-industrial times, causing a measurable reduction in seawater pH and carbonate saturation. If CO2 emissions continue to rise at current rates, upper-ocean pH will decrease to levels lower than have existed for tens of millions of years and, critically, at a rate of change 100 times greater than at any time over this period. Recent studies have shown effects of ocean acidification on a variety of marine life forms, in particular calcifying organisms. Consequences at the community to ecosystem level, in contrast, are largely unknown. Here we show that dissolved inorganic carbon consumption of a natural plankton community maintained in mesocosm enclosures at initial CO2 partial pressures of 350, 700 and 1,050 microatm increases with rising CO2. The community consumed up to 39% more dissolved inorganic carbon at increased CO2 partial pressures compared to present levels, whereas nutrient uptake remained the same. The stoichiometry of carbon to nitrogen drawdown increased from 6.0 at low CO2 to 8.0 at high CO2, thus exceeding the Redfield carbon:nitrogen ratio of 6.6 in today's ocean. This excess carbon consumption was associated with higher loss of organic carbon from the upper layer of the stratified mesocosms. If applicable to the natural environment, the observed responses have implications for a variety of marine biological and biogeochemical processes, and underscore the importance of biologically driven feedbacks in the ocean to global change. 相似文献
146.
Stark A Lin MF Kheradpour P Pedersen JS Parts L Carlson JW Crosby MA Rasmussen MD Roy S Deoras AN Ruby JG Brennecke J;Harvard FlyBase curators;Berkeley Drosophila Genome Project Hodges E Hinrichs AS Caspi A Paten B Park SW Han MV Maeder ML Polansky BJ Robson BE Aerts S van Helden J Hassan B Gilbert DG Eastman DA Rice M Weir M Hahn MW Park Y Dewey CN Pachter L Kent WJ Haussler D Lai EC Bartel DP Hannon GJ Kaufman TC Eisen MB Clark AG Smith D Celniker SE Gelbart WM Kellis M 《Nature》2007,450(7167):219-232
147.
Low beta diversity of herbivorous insects in tropical forests 总被引:1,自引:0,他引:1
Novotny V Miller SE Hulcr J Drew RA Basset Y Janda M Setliff GP Darrow K Stewart AJ Auga J Isua B Molem K Manumbor M Tamtiai E Mogia M Weiblen GD 《Nature》2007,448(7154):692-695
Recent advances in understanding insect communities in tropical forests have contributed little to our knowledge of large-scale patterns of insect diversity, because incomplete taxonomic knowledge of many tropical species hinders the mapping of their distribution records. This impedes an understanding of global biodiversity patterns and explains why tropical insects are under-represented in conservation biology. Our study of approximately 500 species from three herbivorous guilds feeding on foliage (caterpillars, Lepidoptera), wood (ambrosia beetles, Coleoptera) and fruit (fruitflies, Diptera) found a low rate of change in species composition (beta diversity) across 75,000 square kilometres of contiguous lowland rainforest in Papua New Guinea, as most species were widely distributed. For caterpillars feeding on large plant genera, most species fed on multiple host species, so that even locally restricted plant species did not support endemic herbivores. Large plant genera represented a continuously distributed resource easily colonized by moths and butterflies over hundreds of kilometres. Low beta diversity was also documented in groups with differing host specificity (fruitflies and ambrosia beetles), suggesting that dispersal limitation does not have a substantial role in shaping the distribution of insect species in New Guinea lowland rainforests. Similar patterns of low beta diversity can be expected in other tropical lowland rainforests, as they are typically situated in the extensive low basins of major tropical rivers similar to the Sepik-Ramu region of New Guinea studied here. 相似文献
148.
149.
150.
Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite 总被引:6,自引:0,他引:6
Warnecke F Luginbühl P Ivanova N Ghassemian M Richardson TH Stege JT Cayouette M McHardy AC Djordjevic G Aboushadi N Sorek R Tringe SG Podar M Martin HG Kunin V Dalevi D Madejska J Kirton E Platt D Szeto E Salamov A Barry K Mikhailova N Kyrpides NC Matson EG Ottesen EA Zhang X Hernández M Murillo C Acosta LG Rigoutsos I Tamayo G Green BD Chang C Rubin EM Mathur EJ Robertson DE Hugenholtz P Leadbetter JR 《Nature》2007,450(7169):560-565
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