N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
Abstract
Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion. The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein. In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function. We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides. The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans. To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition. We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects. Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
The extent of the benefit of bevacizumab combined with chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) is still unclear. We performed this meta-analysis to compare the efficacy of bevacizumab with other commonly used targeted drugs for different patients with advanced NSCLC.
Methods
We searched PubMed, Cochrane Library, EMBASE and abstracts from the proceedings of the American Society of Clinical Oncology (ASCO), and identified 30 randomized controlled clinical trials published within 1999 to 2011 for meta-analysis.
Results
The outcomes of treatment efficacy included response rate, PFS and OS. Comparing bevacizumab (15 mg/kg) with chemotherapy to standard chemotherapy alone, for chemotherapy-naïve patients, the pooled OR of response rate was 2.741(95%CI: 2.046, 3.672), the pooled HR for disease progression was 0.645 (95%CI: 0.561, 0.743), and the pooled HR for death was 0.790 (95%CI: 0.674, 0.926), respectively. In addition, the adjusted HR for previously-treated patients was 0.680 (95%CI: 0.492, 0.942) comparing bevacizumab combined with chemotherapy to standard chemotherapy alone.
Conclusions
Bevacizumab accompanied by chemotherapy was found to significantly improve patients'' response rate, progression free survival (PFS), and overall survival (OS) among chemotherapy-naïve patients compared to other targeted drugs in the treatment of non-small cell lung carcinoma (NSCLC). 相似文献
This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P<0.01), which were associated with age, sex, the rate of positive TgAb, abnormal thyroid volume, abnormal TSH, and positive personal history of thyroid diseases. The data from 1856 subjects with normal range of thyroid parameters but no personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. Among these three regions, the serum Tg levels were substantially different in both 1999 and 2004, with a similar pattern for increased Tg (ΔTg) (3.1μg/L, 2.5μg/L and 3.5μg/L respectively, P<0.01). The general linear model analysis revealed that age, Tg, and baseline TSH levels were the determinants of ΔTg besides iodine intake. In conclusion, serum Tg in adults, resulting from a time-accumulative effect of iodine exposure, is a useful biomarker of regional iodine intake. 相似文献
This study examined the effect of ASD strain (Aspergillus flavipes), isolated from continuous cropping soil for pepper and named by the sampling position, on soil microflora and soil enzymes in rooting zone soil of healthy and diseased (Phytophthora capsici) pepper plants. Results showed that the ASD strain could significantly reduce the number of bacteria and actinomycetes, with a significant increase in fungi in the rhizosphere soil of both healthy and diseased plants. With increasing colonization time of the ASD strain, the number of bacteria and actinomycetes decreased initially and then increased gradually, while the number of fungi was first increased significantly and later decreased slowly. The soil enzyme activities of urease, acid phosphatase, invertase and dehydrogenase were significantly increased by the ASD strain, while the activity of catalase was not significantly increased. As time from inoculation with the ASD strain increased, the activities of various enzymes were higher than controls. Maximum enzyme activities were found on the tenth day after ADS inoculation. The response of soil enzyme activities affected by the ASD strain was as follows: urease > dehydrogenase > invertase > acid phosphatase > catalase. These results suggest that the biocontrol of ASD strain could improve the micro ecology of rhizosphere soil. 相似文献
The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection. 相似文献