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Abstract: Pharmacologically active agents were employed to study the mechanisms that control the reduction in levels of acetyl-coA: arylamine N-acetyltransferase activity (NAT) (EC 2.3.1.5) in the rat pineal. Pretreatment of rats with phenoxybenzamine or phentolamine prevented the rapid light-mediated decrease in NAT activity, although pretreatment with yohimbine or atropine did not alter this effect of light. Administration of mecamylamine resulted in a rapid reduction in enzyme activity prior to light exposure. When clonidine was administered intraperitoneally to animals with elevated NAT levels, there was a rapid decrease in enzyme activity, mimicking the effects of light. However, intraperitoneal injections of norepinephrine, methoxamine and phenylephrine into similar groups of animals had no significant effect on enzyme acitivity. When clonidine and norepinephrine were administered intraventricularly, there was a rapid reduction in enzyme activity. On the other hand, intraventricular administration of phenylephrine did not result in reduced enzyme activity. Pretreatment of animals with phenoxybenzamine failed to block the reduction in NAT activity precipitated by low doses of clonidine. This clonidine-mediated reduction in enzyme activity was, however, blocked by yohimbine. When animals were simultaneously exposed to light and administered clonidine, the rapid reduction in NAT activity was affected only when animals were pretreated with both yohimbine and phenoxybenzamine. In contrast to the decrease in pineal NAT activity observed in in vivo preparations, incubation of pineals with clonidine in an organ culture system produced a moderate, but consistent, rise in enzyme activity. These results suggest that stimulation of a receptor with α-adrenergic characteristics mediates the reduction in NAT activity produced by light. Stimulation of yet a second adrenergic-like receptor appears to mediate a reduction in pineal NAT activity precipitated by clonidine. Our evidence suggests that one or both of these receptors are located within the central nervous system. 相似文献
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Markus Hoffmann Nadine Krüger Pawel Zmora Florian Wrensch Georg Herrler Stefan P?hlmann 《PloS one》2016,11(3)
New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin. 相似文献
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Peter Van Bogaert Lieve Peremans Nadine Diltour Danny Van heusden Tinne Dilles Bart Van Rompaey Donna Sullivan Havens 《PloS one》2016,11(4)
The aim of the study reported in this article was to investigate staff nurses’ perceptions and experiences about structural empowerment and perceptions regarding the extent to which structural empowerment supports safe quality patient care. To address the complex needs of patients, staff nurse involvement in clinical and organizational decision-making processes within interdisciplinary care settings is crucial. A qualitative study was conducted using individual semi-structured interviews of 11 staff nurses assigned to medical or surgical units in a 600-bed university hospital in Belgium. During the study period, the hospital was going through an organizational transformation process to move from a classic hierarchical and departmental organizational structure to one that was flat and interdisciplinary. Staff nurses reported experiencing structural empowerment and they were willing to be involved in decision-making processes primarily about patient care within the context of their practice unit. However, participants were not always fully aware of the challenges and the effect of empowerment on their daily practice, the quality of care and patient safety. Ongoing hospital change initiatives supported staff nurses’ involvement in decision-making processes for certain matters but for some decisions, a classic hierarchical and departmental process still remained. Nurses perceived relatively high work demands and at times viewed empowerment as presenting additional. Staff nurses recognized the opportunities structural empowerment provided within their daily practice. Nurse managers and unit climate were seen as crucial for success while lack of time and perceived work demands were viewed as barriers to empowerment. 相似文献
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Sixin Jiang Brigitte Heller Vincent S. Tagliabracci Lanmin Zhai Jose M. Irimia Anna A. DePaoli-Roach Clark D. Wells Alexander V. Skurat Peter J. Roach 《The Journal of biological chemistry》2010,285(45):34960-34971
Stbd1 is a protein of previously unknown function that is most prevalent in liver and muscle, the major sites for storage of the energy reserve glycogen. The protein is predicted to contain a hydrophobic N terminus and a C-terminal CBM20 glycan binding domain. Here, we show that Stbd1 binds to glycogen in vitro and that endogenous Stbd1 locates to perinuclear compartments in cultured mouse FL83B or Rat1 cells. When overexpressed in COSM9 cells, Stbd1 concentrated at enlarged perinuclear structures, co-localized with glycogen, the late endosomal/lysosomal marker LAMP1 and the autophagy protein GABARAPL1. Mutant Stbd1 lacking the N-terminal hydrophobic segment had a diffuse distribution throughout the cell. Point mutations in the CBM20 domain did not change the perinuclear localization of Stbd1, but glycogen was no longer concentrated in this compartment. Stable overexpression of glycogen synthase in Rat1WT4 cells resulted in accumulation of glycogen as massive perinuclear deposits, where a large fraction of the detectable Stbd1 co-localized. Starvation of Rat1WT4 cells for glucose resulted in dissipation of the massive glycogen stores into numerous and much smaller glycogen deposits that retained Stbd1. In vitro, in cells, and in animal models, Stbd1 consistently tracked with glycogen. We conclude that Stbd1 is involved in glycogen metabolism by binding to glycogen and anchoring it to membranes, thereby affecting its cellular localization and its intracellular trafficking to lysosomes. 相似文献
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Scaling of metabolic rate with body mass and temperature in teleost fish 总被引:27,自引:0,他引:27
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