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Leptin receptor action and mechanisms of leptin resistance   总被引:13,自引:0,他引:13  
The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004  相似文献   
34.
Kollmann M  Løvdok L  Bartholomé K  Timmer J  Sourjik V 《Nature》2005,438(7067):504-507
Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems.  相似文献   
35.
Zusammenfassung Die Wirkung von protein-, kohlenhydrat-und lipidspaltenden Enzymen auf die Wand von isolierten Metazerkarien ausFasciola hepatica scheint zu zeigen, dass wenigstens Teile der äusseren Schicht aus ziemlich resistentem Protein, das möglicherweise aromatische, basische Aminosäuren, Leucin und Glycin enthält, bestehen. Das Vorkommen von sauren Kohlenhydraten, insbesondere von Hyaluronsäure oder Chondroitinschwefelsäure A oder C in den inneren Schichten ist wahrscheinlich.

Kindly provided by Dr.J. Boray, McMaster Animal Health Laboratory, Glebe (Australia).

Supported by a grant from Jordbrukets Forskningsråd.  相似文献   
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Two decades of scientific ocean drilling have demonstrated widespread microbial life in deep sub-seafloor sediment, and surprisingly high microbial-cell numbers. Despite the ubiquity of life in the deep biosphere, the large community sizes and the low energy fluxes in this vast buried ecosystem are not yet understood. It is not known whether organisms of the deep biosphere are specifically adapted to extremely low energy fluxes or whether most of the observed cells are in a dormant, spore-like state. Here we apply a new approach--the D:L-amino-acid model--to quantify the distributions and turnover times of living microbial biomass, endospores and microbial necromass, as well as to determine their role in the sub-seafloor carbon budget. The approach combines sensitive analyses of unique bacterial markers (muramic acid and D-amino acids) and the bacterial endospore marker, dipicolinic acid, with racemization dynamics of stereo-isomeric amino acids. Endospores are as abundant as vegetative cells and microbial activity is extremely low, leading to microbial biomass turnover times of hundreds to thousands of years. We infer from model calculations that biomass production is sustained by organic carbon deposited from the surface photosynthetic world millions of years ago and that microbial necromass is recycled over timescales of hundreds of thousands of years.  相似文献   
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Bjørnerud MG  Austrheim H 《Nature》2006,440(7082):E4; discussion E4-E4; discussion E5
The mechanisms by which mafic rocks become converted to denser eclogite in the lower crust and mantle are fundamental to our understanding of subduction, mountain building and the long-term geochemical evolution of Earth. Based on larger-than-expected gradients in argon isotopes, Camacho et al. propose a new explanation--co-seismic injection of hot (700 degrees C) aqueous fluids into much colder (400 degrees C) crust--for the localized nature of eclogite metamorphism during Caledonian crustal thickening, as recorded in the rocks of Holsn?y in the Bergen arcs, western Norway. We have studied these unusual rocks, which were thoroughly dehydrated under granulite facies conditions during a Neoproterozoic event (about 945 million years (945 Myr) ago); we also concluded that fracture-hosted fluids were essential as catalysts and components in the conversion to eclogite about 425 Myr ago. However, we are sceptical of the assertion by Camacho et al. that eclogite temperatures were reached only in the vicinity of fluid-filled fractures. Determining whether these rocks were strong enough to fracture at depths of 50 km because they were cold or because they were very dry is crucial to understanding the mechanics of the lower crust in mountain belts, including, for example, the causes of seismicity in the Indian plate beneath the modern Himalayas.  相似文献   
39.
I would like to thank Prof. Stephen Read (2011) and Prof. Andrew Benjamin (2011) for both giving inspiring and elaborate comments on my article “Dwelling in-between walls: the architectural surround”. As I will try to demonstrate below, their two different responses not only supplement my article very nicely, but also augment each other’s. In the beginning of Read’s comment, as he sets the stage for his observations, he unknowingly also points in the direction of Benjamin’s remarks: “I propose not to de-construct therefore, or add a point of view from an orthogonal position, but to try in the spirit of multidisciplinarity to talk in languages not well practiced—to begin to build what Bowker and Star call ‘boundary objects’ between different starting positions; points we can gather around to think further together” (Read 2011). Whereas Read facilitates a multidisciplinary dialogue, Benjamin focuses on how the absence of an initial distinction might threaten the endeavour of my paper. In my reply to Read and Benjamin, I will discuss their suggestions and arguments, while at the same time hopefully clarifying the postphenomenological approach to architecture.  相似文献   
40.
Anaerobic ammonium oxidation by anammox bacteria in the Black Sea   总被引:80,自引:0,他引:80  
The availability of fixed inorganic nitrogen (nitrate, nitrite and ammonium) limits primary productivity in many oceanic regions. The conversion of nitrate to N2 by heterotrophic bacteria (denitrification) is believed to be the only important sink for fixed inorganic nitrogen in the ocean. Here we provide evidence for bacteria that anaerobically oxidize ammonium with nitrite to N2 in the world's largest anoxic basin, the Black Sea. Phylogenetic analysis of 16S ribosomal RNA gene sequences shows that these bacteria are related to members of the order Planctomycetales performing the anammox (anaerobic ammonium oxidation) process in ammonium-removing bioreactors. Nutrient profiles, fluorescently labelled RNA probes, 15N tracer experiments and the distribution of specific 'ladderane' membrane lipids indicate that ammonium diffusing upwards from the anoxic deep water is consumed by anammox bacteria below the oxic zone. This is the first time that anammox bacteria have been identified and directly linked to the removal of fixed inorganic nitrogen in the environment. The widespread occurrence of ammonium consumption in suboxic marine settings indicates that anammox might be important in the oceanic nitrogen cycle.  相似文献   
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