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961.
962.
CD8(+) T cell responses to vaccinia virus are directed almost exclusively against early gene products. The attenuated strain modified vaccinia virus Ankara (MVA) is under evaluation in clinical trials of new vaccines designed to elicit cellular immune responses against pathogens including Plasmodium spp., M. tuberculosis and HIV-1. All of these recombinant MVAs (rMVA) utilize the well-established method of linking the gene of interest to a cloned poxviral promoter prior to insertion into the viral genome at a suitable locus by homologous recombination in infected cells. Using BAC recombineering, we show that potent early promoters that drive expression of non-functional or non-essential MVA open reading frames (ORFs) can be harnessed for immunogenic expression of recombinant antigen. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. The frequency of antigen-specific CD8(+) T cells induced in mice by single shot or adenovirus-prime, rMVA-boost vaccination were similarly equal or marginally enhanced using endogenous promoters at their authentic genomic loci compared to the traditional constructs. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. Furthermore, the growth rates of the viruses were unimpaired and the insertions were genetically stable. Insertion of a transgenic ORF in place of a viral ORF by BAC recombineering can thus provide not only a potent promoter, but also, concomitantly, a suitable insertion site, potentially facilitating development of MVA vaccines expressing multiple recombinant antigens. 相似文献
963.
964.
Abakay A Gokalp O Abakay O Evliyaoglu O Sezgi C Palanci Y Ekici F Karakus A Tanrikulu AC Ayhan M 《Biological trace element research》2012,145(2):151-157
The aim of this study was to investigate the respiratory function disorders that could be related to dust exposure during
the production of copper mine in copper mineworkers (CMWs). The study included 75 male CMWs (mean age, 32.0 ± 7.1 years, 58.6%
smokers) and 75 male age- and smoking status-matched healthy control subjects. Serum Cu level was significantly higher in
the CMW group (0.80 ± 0.62 μg/ml) than the control group (0.60 ± 0.39 μg/ml) (p = 0.017). Significant negative correlations were found between serum Cu level and forced expiratory volume in first second
(r = −0.600; p < 0.001) and between serum Cu level and forced vital capacity (r = −0.593; p = <0.001) in CMWs. Serum Cu level was significantly higher in the restrictive type pulmonary function disorders group (1.36 ± 0.62 μg/ml)
than obstructive type (0.90 ± 0.55 μg/ml) and normal pulmonary function pattern group (0.53 ± 0.43 μg/ml) (p < 0.001). Patients with radiological parenchymal abnormalities had significantly higher serum copper levels than those without
abnormalities (1.53 ± 0.52 vs. 0.71 ± 0.52 μg/ml, respectively; p = 0.002). In conclusion, result of the study has shown a negative association between pulmonary functions disorders and radiological
abnormalities and serum Cu levels in CMWs. 相似文献
965.
Abdullah MA Alzate O Mohammad M McNall RJ Adang MJ Dean DH 《Applied and environmental microbiology》2003,69(9):5343-5353
Bacillus thuringiensis mosquitocidal toxin Cry4Ba has no significant natural activity against Culex quinquefasciatus or Culex pipiens (50% lethal concentrations [LC(50)], >80,000 and >20,000 ng/ml, respectively). We introduced amino acid substitutions in three putative loops of domain II of Cry4Ba. The mutant proteins were tested on four different species of mosquitoes, Aedes aegypti, Anopheles quadrimaculatus, C. quinquefasciatus, and C. pipiens. Putative loop 1 and 2 exchanges eliminated activity towards A. aegypti and A. quadrimaculatus. Mutations in a putative loop 3 resulted in a final increase in toxicity of >700-fold and >285-fold against C. quinquefasciatus (LC(50) congruent with 114 ng/ml) and C. pipiens (LC(50) 37 ng/ml), respectively. The enhanced protein (mutein) has very little negative effect on the activity against Anopheles or AEDES: These results suggest that the introduction of short variable sequences of the loop regions from one toxin into another might provide a general rational design approach to enhancing B. thuringiensis Cry toxins. 相似文献
966.
Rita O Teodoro Gulçin Pekkurnaz Abdullah Nasser Misao E Higashi‐Kovtun Maria Balakireva Ian G McLachlan Jacques Camonis Thomas L Schwarz 《The EMBO journal》2013,32(14):2039-2055
Remodelling neuronal connections by synaptic activity requires membrane trafficking. We present evidence for a signalling pathway by which synaptic activity and its consequent Ca2+ influx activate the small GTPase Ral and thereby recruit exocyst proteins to postsynaptic zones. In accord with the ability of the exocyst to direct delivery of post-Golgi vesicles, constitutively active Ral expressed in Drosophila muscle causes the exocyst to be concentrated in the region surrounding synaptic boutons and consequently enlarges the membrane folds of the postsynaptic plasma membrane (the subsynaptic reticulum, SSR). SSR growth requires Ral and the exocyst component Sec5 and Ral-induced enlargement of these membrane folds does not occur in sec5−/− muscles. Chronic changes in synaptic activity influence the plastic growth of this membrane in a manner consistent with activity-dependent activation of Ral. Thus, Ral regulation of the exocyst represents a control point for postsynaptic plasticity. This pathway may also function in mammals as expression of activated RalA in hippocampal neurons increases dendritic spine density in an exocyst-dependent manner and increases Sec5 in spines. 相似文献
967.
968.
Narasimha Reddy Parine Nahla A. Azzam Jilani Shaik Abdulrahman M. Aljebreen Othman Alharbi Majid A. Almadi Mohammad Alanazi Zahid Khan 《Saudi Journal of Biological Sciences》2019,26(2)
The Wnt/β-catenin signaling pathway has been etiologically implicated in the development and progression of colorectal cancer. We studied thirteen single nucleotide polymorphisms (SNPs) located in SFRP3 (rs7775), CTNNB1 (β-catenin) [rs4135385, rs13072632], APC (rs454886, rs459552), LRP6 (rs2075241, rs2284396), DKK4 (rs3763511), DKK3 (rs6485350), TCF4 (rs12255372) and AXIN2 (rs3923086, rs3923087, rs4791171) in patients with colorectal cancer (n?=?122) and controls (n?=?110). Evaluation of WNT pathway SNPs showed protective association for rs4135385, located in β-catenin. Additionally, variants in SFRP3 (rs7775) and LRP6 (rs2284396) which did not show any association in the overall analysis were significantly associated with female and old aged colorectal cancer patients, respectively. 相似文献
969.
970.
Böyük A Banlı O Gümüş M Evliyaoğlu O Demirelli S 《Biological trace element research》2011,143(3):1282-1288
Laparoscopic adjustable gastric banding (LAGB) causes significant weight loss in morbidly obese adults. However, its consequences
on nutritional status still remain unclear. There are a few studies determining the nutritional status after LAGB and none
have focused on the serum levels of zinc (Zn), copper (Cu), and ceruloplasmin (CP). We aimed to investigate the effects of
LAGB surgery on plasma Zn, Cu, and CP levels. Thirty patients with LAGB with morbid obesity were included. Blood samples were
collected preooperatively and in the postoperative third month to determine plasma Zn, Cu, and CP levels. The mean preoperative
and postoperative body mass indexes (BMI) were 44.9 ± 7.4 kg/m2 and 44.1 ± 6.5 kg/m2, respectively. The mean weight loss was 12.9 ± 3.3 kg at the postoperative third month. The postoperative Zn (500 ± 130 ng/ml),
Cu (280 ± 80 ng/ml), and CP (23.9 ± 8.8 mg/dl) values were statistically significantly lower than the preooperative Zn (740 ± 230 ng/ml),
Cu (370 ± 80 ng/ml) and CP (33.3 ± 15.7 mg/dl) levels (p < 0.05). Decreases in the plasma levels of Zn, Cu, and CP were seen postoperatively following LAGB surgery. The nutritional
status of LAGB-applied patients should be monitored and mineral supplementation may be considered. 相似文献