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L B Rall J Scott G I Bell R J Crawford J D Penschow H D Niall J P Coghlan 《Nature》1985,313(5999):228-231
Epidermal growth factor (EGF), a protein comprising 53 amino acids, is derived from a precursor of 1,217 amino acids that includes at least seven EGF-like sequences. EGF has diverse biological activities: it is a potent mitogen for many tissue culture cells, inhibits gastric acid secretion from the intestinal mucosa and promotes healing of the corneal epithelium. EGF given to fetal animals accelerates several developmental processes including palate formation, incisor eruption, eyelid opening and lung maturation. However, the physiological roles of EGF in vivo are unknown. The presence of high-affinity receptors in many fetal and adult tissues suggests that EGF is involved in normal cellular functions. Immunocytochemical studies have revealed the presence of EGF in mouse and human submaxillary glands, rat brain and human intestine. The low levels of EGF in extracts from many tissues may reflect sequestration rather than synthesis of the polypeptide. We show here that several mouse tissues contain preproEGF mRNA and that it is synthesized mainly in the distal tubules of the kidney. PreproEGF does not seem to be processed to EGF or other peptides in this tissue. 相似文献
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Kobayashi YM Rader EP Crawford RW Iyengar NK Thedens DR Faulkner JA Parikh SV Weiss RM Chamberlain JS Moore SA Campbell KP 《Nature》2008,456(7221):511-515
Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling. 相似文献
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We examined Blue Grouse ( Dendragapus obscurus ) nesting characteristics in northeastern Oregon to identify relationships between hen age and nesting parameters and to ascertain habitat charactersicts related to successful nests. Adult and yearling hens exhibited no differences in clutch size, percentage of eggs hatched, nesting success, or hatch dates. Among nests located under logs, 100% ( n =10) hatched ≥ 1 egg, whereas 58% ( n = 10) of 17 nests not under logs hatched ≥ 1 egg. 相似文献
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Sage Grouse ( Centrocercus urophasianus ) brood-habitat use was examined during 1992 and 1993 at the Yakima Training Center in Yakima and Kittitas counties, Washington. During the 2 yr we followed 30 broods, of which 12 persisted to 1 August ( ̄ x = approximately 1.5 chicks/brood). Food forb cover was greater at all brood locations than at random locations. Hens with broods in big sagebrush/bunchgrass habitat ( Artemisia tridentata/Agropyron spicatum ) selected for greater food forb cover, total forb cover, and lower shrub heights; broods in altered big sagebrush/bunchgrass habitats selected greater tall grass cover and vertical cover height; broods in grassland showed no preference for any measured vegetation characteristics. During the early rearing period (post-hatching-6 wk) each year, broods selected sagebrush/bunchgrass. Broods in 1993 made greater use of grasslands than in 1992 and selected grassland during the late brood-rearing period (7-12 wk). Broods selected for sagebrush/bunchgrass during the midday, but 52% of brood locations in the afternoon were in grassland. Tall grass cover was greater at morning (0500-1000 h) and afternoon (1501-2000 h) brood locations than at midday (1001-1500 h) and random locations. Midday brood locations had greater shrub cover and height than morning and afternoon locations. Selection of habitat components was similar to the results of other studies, but habitat conditions coupled with a possible lack of alternate brood-rearing cover types resulted in low survival of chicks. 相似文献
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Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
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