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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 485-516 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Integrins are a structurally elaborate family of heterodimers that mediate divalent cation-dependent cell adhesion in a wide range of biological contexts. The inserted (I) domain binds ligand in the subset of integrins in which it is present. Its structure has been determined in two alternative conformations, termed open and closed. In striking similarity to signaling G proteins, rearrangement of a Mg2+-binding site is linked to large conformational movements in distant backbone regions. Mutations have been used to stabilize either the closed or open structures. These show that the snapshots of the open conformation seen only in the presence of a ligand or a ligand mimetic represent a high-affinity, ligand-binding conformation, whereas those of the closed conformation correspond to a low-affinity conformation. The C-terminal alpha-helix moves 10 A down the side of the domain in the open conformation. Locking in the conformation of the preceding loop is sufficient to increase affinity for ligand 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to conformational movements in other domains. The transition from the closed to open conformation has been implicated in fast (〈1 s) regulation of integrin affinity in response to activation signals from inside the cell. Recent integrin structures and functional studies reveal interactions between beta-propeller, I, and I-like domains in the headpiece, and a critical role for integrin EGF domains in the stalk region. These studies suggest that the headpiece of the integrin faces down toward the membrane in the inactive conformation and extends upward in a "switchblade"-like opening motion upon activation. These long-range structural rearrangements of the entire integrin molecule involving multiple interdomain contacts appear closely linked to conformational changes in the I domain, which result in increased affinity and competence for ligand binding.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 25 (1998), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1438-8359
    Keywords: Multiple vein of Galen aneurysms ; Persistent fetal circulation ; Three-dimensional computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1072-8368
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] We have taken a computational approach to design mutations that stabilize a large protein domain of ∼200 residues in two alternative conformations. Mutations in the hydrophobic core of the αMβ2 integrin I domain were designed to stabilize the crystallographically defined open or ...
    Type of Medium: Electronic Resource
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