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排序方式: 共有144条查询结果,搜索用时 293 毫秒
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Rui M Costa Nikolai B Federov Jeff H Kogan Geoffrey G Murphy Joel Stern Masuo Ohno Raju Kucherlapati Tyler Jacks Alcino J Silva 《Nature》2002,415(6871):526-530
Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1. 相似文献
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Irina Kerkis Alvaro Rossan de Brandão Prieto da Silva Celine Pompeia Jan Tytgat Paulo L. de Sá Junior 《Cellular and molecular life sciences : CMLS》2017,74(4):647-661
Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides—a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity. 相似文献
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da Silva Copertino M 《Nature》2011,473(7347):255
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Bedding TR Mosser B Huber D Montalbán J Beck P Christensen-Dalsgaard J Elsworth YP García RA Miglio A Stello D White TR De Ridder J Hekker S Aerts C Barban C Belkacem K Broomhall AM Brown TM Buzasi DL Carrier F Chaplin WJ Di Mauro MP Dupret MA Frandsen S Gilliland RL Goupil MJ Jenkins JM Kallinger T Kawaler S Kjeldsen H Mathur S Noels A Aguirre VS Ventura P 《Nature》2011,471(7340):608-611
Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ~ 50 seconds) and those that are also burning helium (period spacing ~ 100 to 300 seconds). 相似文献
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Sicardy B Ortiz JL Assafin M Jehin E Maury A Lellouch E Hutton RG Braga-Ribas F Colas F Hestroffer D Lecacheux J Roques F Santos-Sanz P Widemann T Morales N Duffard R Thirouin A Castro-Tirado AJ Jelínek M Kubánek P Sota A Sánchez-Ramírez R Andrei AH Camargo JI da Silva Neto DN Gomes AR Martins RV Gillon M Manfroid J Tozzi GP Harlingten C Saravia S Behrend R Mottola S Melendo EG Peris V Fabregat J Madiedo JM Cuesta L Eibe MT Ullán A Organero F Pastor S de Los Reyes JA Pedraz S Castro A 《Nature》2011,478(7370):493-496
The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ~1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun. 相似文献
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Hummingbirds have developed a wealth of intriguing features, such as backwards flight, ultraviolet vision, extremely high metabolic rates, nocturnal hibernation, high brain-to-body size ratio and a remarkable species-specific diversity of vocalizations. Like humans, they have also developed the rare trait of vocal learning, this being the ability to acquire vocalizations through imitation rather than instinct. Here we show, using behaviourally driven gene expression in freely ranging tropical animals, that the forebrain of hummingbirds contains seven discrete structures that are active during singing, providing the first anatomical and functional demonstration of vocal nuclei in hummingbirds. These structures are strikingly similar to seven forebrain regions that are involved in vocal learning and production in songbirds and parrots--the only other avian orders known to be vocal learners. This similarity is surprising, as songbirds, parrots and hummingbirds are thought to have evolved vocal learning and associated brain structures independently, and it indicates that strong constraints may influence the evolution of forebrain vocal nuclei. 相似文献