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ABSTRACTSleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding. 相似文献
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J L Pipkin W G Hinson S J James J G Shaddock L E Lyn-Cook R J Feuers S M Morris W H Tolleson D A Casciano 《Biochimica et biophysica acta》1999,1450(2):164-176
A single, i.p. dose of bleomycin was administered simultaneously with [35S]methionine to 4-month-old p53 wild type (+/+) and p53 heterozygous (+/-) C57BL/6 mice. Following a period of 3.5 h from dosing, the bone marrow nuclei were examined by two-dimensional PAGE and fluorography for induction of stress proteins (sps). Eight sps ranging from 22000 to 100000 Mr were synthesized in p53+/- and p53+/+ mice following elicitation by bleomycin. No quantitative or qualitative differences were observed in sp expression in these two groups of animals. In a second experiment, three doses of retinoic acid were given i.p. to p53+/- and p53+/+ mice over a 36 h period. The p53 isoforms in bone marrow nuclei from these mice were analyzed by PAGE for incorporation of [35S]methionine following retinoic acid injections. Quantitative and qualitative alterations in p53 isotypes were substantially increased in p53+/+ as compared with p53+/- mice. The increased complexity in the synthesis patterns in both groups of dosed mice consisted of additional isoforms possessing more acidic isoelectric values. In an in vitro binding assay, individual p53 isoforms demonstrated varying degrees of association with sps 25a, 70i, 72c and 90 which was consistently greater in p53+/+ mice. Both the synthesis and binding of isoforms were greater in G1 than in S+G2 phase, in both groups of animals, reflecting a cell cycle regulated mechanism for these events. Collectively, these data implied that the synthesis and the binding characteristics of p53 isoforms with sps were enhanced in the p53+/+ mice relative to the p53+/- mouse; however, sp labeling was not affected by p53 genotype. 相似文献
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Viperin is an evolutionarily conserved interferon-inducible protein that
localizes to the endoplasmic reticulum (ER) and inhibits a number of DNA and
RNA viruses. In this study, we report that viperin specifically localizes to
the cytoplasmic face of the ER and that an amphipathic α-helix at its N
terminus is necessary for the ER localization of viperin and sufficient to
promote ER localization of a reporter protein, dsRed. Overexpression of intact
viperin but not the amphipathic α-helix fused to dsRed induced
crystalloid ER. Consistent with other proteins that induce crystalloid ER,
viperin self-associates, and it does so independently of the amphipathic
α-helix. Viperin expression also affected the transport of soluble but
not membrane-associated proteins. Expression of intact viperin or an
N-terminal α-helix-dsRed fusion protein significantly reduced secretion
of soluble alkaline phosphatase and reduced its rate of ER-to-Golgi
trafficking. Similarly, viperin expression inhibited bulk protein secretion
and secretion of endogenous α1-antitrypsin and serum albumin
from HepG2 cells. Converting hydrophobic residues in the N-terminal
α-helix to acidic residues partially or completely restored normal
transport of soluble alkaline phosphatase, suggesting that the extended
amphipathic nature of the N-terminal α-helical domain is essential for
inhibiting protein secretion.Type I interferons are the first line of defense against viral infections.
The significance of the interferon pathway is illustrated by the
susceptibility of interferon signaling mutants to infection and by viral
mechanisms that counteract this pathway
(1,
2). Although many genes are
induced upon interferon stimulation, very few of these genes have been
functionally characterized. Viperin is highly induced by both Type I and II
interferons and has a broad range of antiviral activity, inhibiting DNA
viruses, notably human cytomegalovirus
(3); RNA viruses such as
influenza, hepatitis C virus
(HCV),2 and
alphaviruses
(4-6);
and retroviruses such as human immunodeficiency virus
(7). Upon expression, viperin
localizes to the endoplasmic reticulum (ER), where it interacts with
farnesyl-diphosphate synthase, an enzyme involved in lipid biosynthesis. This
interaction appears to result in the disruption of lipid raft microdomains and
prevention of influenza virus from budding from the plasma membrane
(4).Although recent studies have explored the antiviral functions of viperin,
the general biochemical properties of this protein remain largely undefined.
Viperin is highly conserved across both mammals and lower vertebrates and
shares homology with the MoaA family of “radical
S-adenosylmethionine” enzymes that bind Fe-S clusters
(3,
8). In addition to a putative
Fe-S cluster-binding domain, viperin has a 42-amino acid residue N-terminal
amphipathic α-helix, and similar domains in other proteins have been
shown to bind membranes and induce membrane curvature
(9,
10).In this study, we examined the role of the viperin N-terminal
α-helical domain in both cellular localization and ER membrane
morphology and analyzed the biochemical properties of viperin. We discovered
that viperin forms dimers and induces a tightly ordered, visually striking
array of ER membranes, known as crystalloid
ER(11-13),
upon overexpression. In addition, viperin expression impedes the secretion of
a variety of soluble proteins. Although the N-terminal amphipathic
α-helix is not sufficient to induce crystalloid ER formation, it is both
necessary and sufficient to mediate ER localization and to inhibit protein
secretion. 相似文献