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71.
Rodríguez-Muñoz M Sánchez-Blázquez P Vicente-Sánchez A Bailón C Martín-Aznar B Garzón J 《Cellular and molecular life sciences : CMLS》2011,68(17):2933-2949
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR.
These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic
effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein
1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented
and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive
to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism.
Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength.
Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms
independent of NMDAR. 相似文献
72.
Lopez-Castejón G Baroja-Mazo A Pelegrín P 《Cellular and molecular life sciences : CMLS》2011,68(18):3095-3107
Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage
polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to
the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes
are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified
as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with
PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the
resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study
reveals an additional level of plasticity modulating the resolution of inflammation. 相似文献
73.
Functional cartography of complex metabolic networks 总被引:16,自引:0,他引:16
High-throughput techniques are leading to an explosive growth in the size of biological databases and creating the opportunity to revolutionize our understanding of life and disease. Interpretation of these data remains, however, a major scientific challenge. Here, we propose a methodology that enables us to extract and display information contained in complex networks. Specifically, we demonstrate that we can find functional modules in complex networks, and classify nodes into universal roles according to their pattern of intra- and inter-module connections. The method thus yields a 'cartographic representation' of complex networks. Metabolic networks are among the most challenging biological networks and, arguably, the ones with most potential for immediate applicability. We use our method to analyse the metabolic networks of twelve organisms from three different superkingdoms. We find that, typically, 80% of the nodes are only connected to other nodes within their respective modules, and that nodes with different roles are affected by different evolutionary constraints and pressures. Remarkably, we find that metabolites that participate in only a few reactions but that connect different modules are more conserved than hubs whose links are mostly within a single module. 相似文献
74.
Two experiments are reported which investigate the factors that influence how persuaded mathematicians are by visual arguments. We demonstrate that if a visual argument is accompanied by a passage of text which describes the image, both research-active mathematicians and successful undergraduate mathematics students perceive it to be significantly more persuasive than if no text is given. We suggest that mathematicians’ epistemological concerns about supporting a claim using visual images are less prominent when the image is described in words. Finally we suggest that empirical studies can make a useful contribution to our understanding of mathematical practice. 相似文献
75.
76.
Respiration in the open ocean 总被引:11,自引:0,他引:11
A key question when trying to understand the global carbon cycle is whether the oceans are net sources or sinks of carbon. This will depend on the production of organic matter relative to the decomposition due to biological respiration. Estimates of respiration are available for the top layers, the mesopelagic layer, and the abyssal waters and sediments of various ocean regions. Although the total open ocean respiration is uncertain, it is probably substantially greater than most current estimates of particulate organic matter production. Nevertheless, whether the biota act as a net source or sink of carbon remains an open question. 相似文献
77.
78.
Gbor . Zempln 《Studies in history and philosophy of science》2006,37(4):585-609
Otto Neurath’s thoroughgoing anti-foundationalism is connected to the recognition that protocol sentences are not inviolable, that is they are fallible and their choice cannot be determined: ‘Poincaré, Duhem and others have adequately shown that even if we have agreed on the protocol statements, there is a not limited number of equally applicable, possible systems of hypotheses. We have extended this tenet of the uncertainty of systems of hypotheses to all statements, including protocol statements that are alterable in principle’ (Neurath, 1983, p. 105). Later historiography has called Neurath’s extension of Duhemian holism the Neurath principle. Based on a study of Neurath’s early works on the history of optics, the paper investigates a previously unnoticed influence on the development of this principle, Neurath’s reading of Goethe’s Theory of colours. The historical and polemical parts of Goethe’s tripartite book provided Neurath with ideal examples for the vertical extension of Duhem’s thesis to observation statements. Moreover, Goethe’s critique of the language of science and his views on the theory-ladenness of observation, as well as on the history of science show strong parallels to many of Neurath’s ideas. These demonstrate the existence of surprisingly direct textual links between Romantic views on science and the development of twentieth-century philosophy of science. Neurath’s usage of Goethe’s examples also indicates that the birth of the Neurath principle is more tightly connected to actual scientific practice than to theory-testing, and that by admitting the theory-ladenness of observation reports and fallibility of protocol statements Neurath does not throw empiricism overboard. 相似文献
79.
L Feliubadaló M Font J Purroy F Rousaud X Estivill V Nunes E Golomb M Centola I Aksentijevich Y Kreiss B Goldman M Pras D L Kastner E Pras P Gasparini L Bisceglia E Beccia M Gallucci L de Sanctis A Ponzone G F Rizzoni L Zelante M T Bassi A L George M Manzoni A De Grandi M Riboni J K Endsley A Ballabio G Borsani N Reig E Fernández R Estévez M Pineda D Torrents M Camps J Lloberas A Zorzano M Palacín 《Nature genetics》1999,23(1):52-57
80.
L. A. García-Alonso 《Cellular and molecular life sciences : CMLS》1999,55(11):1386-1398
The peripheral sensory system of the Drosophila adult has been used for the genetic analysis of axon guidance because of its accessibility for experimental manipulation
and mutant screens. Wing, leg, antenna, or eye sensory axons are able to pathfind normally under different perturbations,
indicating that sensory axon guidance is a highly canalized process. Similarly to other model systems, sensory growth cones
seem to use multiple, simultaneous cues for guidance. In addition, sensory axons from peripheral structures seem to be capable
of using alternative substrates for pathfinding. Developmental regulation could account for the high stability of axon guidance
under experimental and natural perturbation conditions. Despite this flexibility, functional characterization of genes involved
in sensory axon guidance is being carried out in situations where there appears to be less system redundancy. 相似文献