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Murine CXCR-4 is a functional coreceptor for T-cell-tropic and dual-tropic strains of human immunodeficiency virus type 1. 总被引:3,自引:2,他引:1
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The human chemokine receptor hCXCR-4 serves as a coreceptor for T-cell-tropic (T-tropic) and dual-tropic strains of human immunodeficiency virus type 1 (HIV-1). We have isolated a homolog of hCXCR-4 from a murine T-cell cDNA library and have examined its ability to function as an HIV-1 coreceptor. mCXCR-4 was found to be 91% identical to the human receptor at the amino acid level, with sequence differences concentrated in extracellular domains. Surprisingly, coexpression of both hCD4 and mCXCR-4 on either simian or murine cell lines rendered them permissive for HIV-1-induced cell fusion, indicating that mCXCR-4 is a functional HIV-1 coreceptor. As with hCXCR-4, coreceptor function was restricted to T-tropic and dual-tropic HIV-1 strains. Ribonuclease protection analysis indicated that mCXCR-4 mRNA was expressed in only two of six murine cell lines tested. In contrast, Northern blot analysis of human and mouse tissues revealed that CXCR-4 is widely expressed in both species in vivo. Overall, these data suggest that the reported lack of susceptibility of hCD4+ murine cells to HIV-1 infection in vitro is, at least in part, due to a lack of mCXCR-4 expression rather than a lack of coreceptor function. 相似文献
3.
Henrik Sundh Bjørn Olav Kvamme Frode Fridell Rolf Erik Olsen Tim Ellis Geir Lasse Taranger Kristina Sundell 《BMC physiology》2010,10(1):22
Background
Fish farmed under high intensity aquaculture conditions are subjected to unnatural environments that may cause stress. Therefore awareness of how to maintain good health and welfare of farmed fish is important. For Atlantic salmon held in sea cages, water flow, dissolved oxygen (DO) levels and temperature will fluctuate over time and the fish can at times be exposed to detrimentally low DO levels and high temperatures. This experimental study investigates primary and secondary stress responses of Atlantic salmon post smolts to long-term exposure to reduced and fluctuating DO levels and high water temperatures, mimicking situations in the sea cages. Plasma cortisol levels and cortisol release to the water were assessed as indicators of the primary stress response and intestinal barrier integrity and physiological functions as indicators of secondary responses to changes in environmental conditions. 相似文献4.
Zheng X Hudyma TW Martin SW Bergstrom C Ding M He F Romine J Poss MA Kadow JF Chang CH Wan J Witmer MR Morin P Camac DM Sheriff S Beno BR Rigat KL Wang YK Fridell R Lemm J Qiu D Liu M Voss S Pelosi L Roberts SB Gao M Knipe J Gentles RG 《Bioorganic & medicinal chemistry letters》2011,21(10):2925-2929
Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC50 = 0.07 μM, %F = 18), are reported. 相似文献
5.
Yen-Chin Liu Alice YW Chang Yu-Chuan Tsai Julie YH Chan 《Journal of biomedical science》2009,16(1):8-14
Background
Both overproduction of nitric oxide (NO) and oxidative injury of cardiovascular and pulmonary systems contribute to fatal cardiovascular depression during endotoxemia. We investigated in the present study the relative contribution of oxidative stress and NO to cardiovascular depression during different stages of endotoxemia, and delineated their roles in cardiovascular protective effects of a commonly used anesthetic propofol during endotoxemia. 相似文献6.
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Fragile X syndrome results from lack of expression of a functional form of Fragile X mental retardation protein (FMRP), a cytoplasmic RNA-binding protein of uncertain function. Here, we report that FMRP contains a nuclear export signal (NES) that is similar to the NES recently identified in the Rev regulatory protein of human immunodeficiency virus type 1 (HIV-1). Mutation of this FMRP NES results in mis-localization of FMRP to the cell nucleus. The FMRP NES is encoded within exon 14 of the FMR1 gene, thus explaining the aberrant nuclear localization of a natural isoform of FMRP that lacks this exon. The NES of FMRP can substitute fully for the Rev NES in mediating Rev-dependent nuclear RNA export and specifically binds a nucleoporin-like cellular cofactor that has been shown to mediate Rev NES function. Together, these findings demonstrate that the normal function of FMRP involves entry into the nucleus followed by export via a pathway that is identical to the one utilized by HIV-1 Rev. In addition, these data raise the possibility that FMRP could play a role in mediating the nuclear export of its currently undefined cellular RNA target(s). 相似文献
8.
Epilepsy is considered one of the most common neurological disorders worldwide. The burst firing neurons associated with prolonged
epileptic discharges could lead to a large number of changes with events of cascades at the cellular level. From its role
as the cellular powerhouse, mitochondria also play a crucial role in the mechanisms of cell death. Emerging evidence has shown
that prolonged seizures may result in mitochondrial dysfunction and increase of oxidative and nitrosative stress in the hippocampus
that precede neuronal cell death and cause subsequent epileptogenesis. The selective dysfunction of mitochondrial respiratory
chain Complex I has been suggested to be a biochemical hallmark of seizure-induced neuronal cell death and epileptogenesis.
Therefore, protection of mitochondria from bioenergetic failure and oxidative stress in the hippocampus may open a new vista
to the development of effective neuroprotective strategies against seizure-induced brain damage and to the design of novel
treatment perspectives against therapy-resistant forms of epilepsy. 相似文献
9.
Identification and Functional Characterization of a Novel Nuclear Localization Signal Present in the Yeast Nab2 Poly(A)+ RNA Binding Protein
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Ray Truant Robert A. Fridell R. Edward Benson Hal Bogerd Bryan R. Cullen 《Molecular and cellular biology》1998,18(3):1449-1458
The nuclear import of proteins bearing a basic nuclear localization signal (NLS) is dependent on karyopherin α/importin α, which acts as the NLS receptor, and karyopherin β1/importin β, which binds karyopherin α and mediates the nuclear import of the resultant ternary complex. Recently, a second nuclear import pathway that allows the rapid reentry into the nucleus of proteins that participate in the nuclear export of mature mRNAs has been identified. In mammalian cells, a single NLS specific for this alternate pathway, the M9 NLS of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), has been described. The M9 NLS binds a transport factor related to karyopherin β1, termed karyopherin β2 or transportin, and does not require a karyopherin α-like adapter protein. A yeast homolog of karyopherin β2, termed Kap104p, has also been described and proposed to play a role in the nuclear import of a yeast hnRNP-like protein termed Nab2p. Here, we define a Nab2p sequence that binds to Kap104p and that functions as an NLS in both human and yeast cells despite lacking any evident similarity to basic or M9 NLSs. Using an in vitro nuclear import assay, we demonstrate that Kap104p can direct the import into isolated human cell nuclei of a substrate containing a wild-type, but not a defective mutant, Nab2p NLS. In contrast, other NLSs, including the M9 NLS, could not function as substrates for Kap104p. Surprisingly, this in vitro assay also revealed that human karyopherin β1, but not the Kap104p homolog karyopherin β2, could direct the efficient nuclear import of a Nab2p NLS substrate in vitro in the absence of karyopherin α. These data therefore identify a novel NLS sequence, active in both yeast and mammalian cells, that is functionally distinct from both basic and M9 NLS sequences. 相似文献
10.
Relationships in the Drosophila obscura species group, inferred from mitochondrial cytochrome oxidase II sequences 总被引:2,自引:0,他引:2
We compare the sequences for the mitochondrial cytochrome oxidase II gene
of 13 species of the Drosophila obscura group. The survey includes six
members of the D. affinis subgroup, four of the D. pseudoobscura subgroup,
and three of the D. obscura subgroup. In all species, the gene is 688
nucleotides in length, encoding a protein of 229 amino acids plus the first
position T of the stop codon. The sequences show the typical
high-transition bias for closely related species, but that bias is
essentially eliminated for species pairs of > 5% sequence divergence.
The phylogenetic relationships in the species group are inferred using both
neighbor-joining and maximum parsimony. The two procedures give comparable
results, showing that the D. affinis and D. pseudoobscura subgroups are
monophyletic groupings that appear to have closer affinities to one another
than either has to the D. obscura subgroup. We use transversion distances
to estimate times of divergence, on the basis of three different estimates
of the time of separation of the D. obscura species group from the D.
melanogaster group. If that event occurred 35 Mya, then we can estimate the
origin of the nearctic forms at approximately 22 Mya and the separation of
the D. affinis and D. pseudoobscura subgroups at approximately 17 Mya.
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