FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activation and downstream signaling are important for neuronal function. Activation of prosurvival Src family kinases and extracellular signal-regulated kinase (ERK) 1/2 is initiated by NMDAR activation, but the cellular organization of these kinases in relation to NMDARs is not entirely clear. We hypothesized that caveolin-1 scaffolds and coordinates protein complexes involved in NMDAR signaling and that this organization is necessary for neuronal preconditioning, whereby NMDAR activation protects neurons from subsequent ischemic cell death. ⋯ Cultures of primary neurons treated with caveolin-1 small interfering RNA or from caveolin-1(-/-) mice lacked the NMDA-mediated increase in P-Src and P-ERK, as well as SLI- and NMDA-induced preconditioning. Adenovirally mediated expression of caveolin-1 in neurons from caveolin-1(-/-) mice restored NMDA-mediated enhancement of P-Src and P-ERK1/2, redistributed NMDAR2B to buoyant fractions, and enhanced NMDAR2B localization to membrane rafts. We conclude that caveolin-1, perhaps via its ability to scaffold key signaling components, is essential for NMDAR localization to neuronal membrane rafts, NMDAR/Src tyrosine kinase family/ERK signaling, and protection of neurons from ischemic injury and cell death.
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Comparative Study
Comparison of PubMed, Scopus, Web of Science, and Google Scholar: strengths and weaknesses.
The evolution of the electronic age has led to the development of numerous medical databases on the World Wide Web, offering search facilities on a particular subject and the ability to perform citation analysis. We compared the content coverage and practical utility of PubMed, Scopus, Web of Science, and Google Scholar. The official Web pages of the databases were used to extract information on the range of journals covered, search facilities and restrictions, and update frequency. ⋯ PubMed remains an optimal tool in biomedical electronic research. Scopus covers a wider journal range, of help both in keyword searching and citation analysis, but it is currently limited to recent articles (published after 1995) compared with Web of Science. Google Scholar, as for the Web in general, can help in the retrieval of even the most obscure information but its use is marred by inadequate, less often updated, citation information.
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Editorial Historical Article
"Spinal irritation" and fibromyalgia: a Surgeon General and The Three Graces.
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Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. We have used the high contrast and spatial resolution of phase contrast X-ray imaging to study lung aeration at birth in spontaneously breathing neonatal rabbits. ⋯ We report the first detailed observations and measurements of lung aeration, demonstrating its dependence on inspiratory activity and body position; dependent regions aerated at much slower rates. The air/liquid interface moved toward the distal airways only during inspiration, with little proximal movement during expiration, indicating that trans-pulmonary pressures play an important role in airway liquid clearance at birth. Using these imaging techniques, the dynamics of lung aeration and the critical role it plays in regulating the physiological changes at birth can be fully explored.
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Vasoconstriction and vascular medial hypertrophy, resulting from increased intracellular [Ca2+] in pulmonary artery smooth muscle cells (PASMC), contribute to elevated vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Caveolae, microdomains within the plasma membrane, contain the protein caveolin, which binds certain signaling molecules. We tested the hypothesis that PASMC from IPAH patients express more caveolin-1 (Cav-1) and caveolae, which contribute to increased capacitative Ca2+ entry (CCE) and DNA synthesis. ⋯ Increased caveolin and caveolae expression thus contribute to IPAH-PASMC pathophysiology. The close relationship between caveolin/caveolae expression and altered cell physiology in IPAH contrast with previous results obtained in various animal models, including caveolin-knockout mice, thus emphasizing unique features of the human disease. The results imply that disruption of caveolae in PASMC may provide a novel therapeutic approach to attenuate disease manifestations of IPAH.