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111.
Ryan Haryadi Steven Ho Yee Jiun Kok Helen X. Pu Lu Zheng Natasha A. Pereira Bin Li Xuezhi Bi Lin-Tang Goh Yuansheng Yang Zhiwei Song 《PloS one》2015,10(2)
Translocation of a nascent protein from the cytosol into the ER mediated by its signal peptide is a critical step in protein secretion. The aim of this work was to develop a platform technology to optimize the signal peptides for high level production of therapeutic antibodies in CHO cells. A database of signal peptides from a large number of human immunoglobulin (Ig) heavy chain (HC) and kappa light chain (LC) was generated. Most of the HC signal peptides contain 19 amino acids which can be divided into three domains and the LC signal peptides contain 22 amino acids. The signal peptides were then clustered according to sequence similarity. Based on the clustering, 8 HC and 2 LC signal peptides were analyzed for their impacts on the production of 5-top selling antibody therapeutics, namely, Herceptin, Avastin, Remicade, Rituxan, and Humira. The best HC and LC signal peptides for producing these 5 antibodies were identified. The optimized signal peptides for Rituxan is 2-fold better compared to its native signal peptides which are available in the public database. Substitution of a single amino acid in the optimized HC signal peptide for Avastin reduced its production significantly. Mass spectrometry analyses revealed that all optimized signal peptides are accurately removed in the mature antibodies. The results presented in this report are particularly important for the production of these 5 antibodies as biosimilar drugs. They also have the potential to be the best signal peptides for the production of new antibodies in CHO cells. 相似文献
112.
113.
Yong-Soo Kwon Yee Hyung Kim Kyeongman Jeon Byeong-Ho Jeong Yon Ju Ryu Jae Chol Choi Ho Cheol Kim Won-Jung Koh 《PloS one》2015,10(6)
Background
Interferon-γ release assays such as the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infections, whether latent or manifesting as disease. However, a substantial number of persons with culture-confirmed tuberculosis (TB) have negative QFT-GITs. Information on host factors contributing to false-negative and indeterminate results are limited.Methods
A multicenter retrospective cohort study was performed with 1,264 culture-confirmed TB patients older than 18 years who were subjected to the QFT-GIT at one of the six hospitals between May 2007 and February 2014. Patients with human immunodeficiency virus infection were excluded. Clinical and laboratory data were collected in South Korea.Results
Of all patients, 87.6% (1,107/1,264) were diagnosed with pulmonary TB and 12.4% (157/1,264) with extrapulmonary TB. The rate of negative results was 14.4% (182/1,264). The following factors were highly correlated with false-negative results in the QFT-GIT: advanced age (age ≥ 65 years, odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03–2.39), bilateral disease as determined by chest radiography (OR 1.75, 95% CI 1.13–2.72), malignancy (OR 2.42, 95% CI 1.30–4.49), and lymphocytopenia (total lymphocyte count < 1.0 × 109/L, OR 1.86, 95% CI 1.21–2.87).Conclusions
Consequently, QFT-GIT results need to be interpreted with caution in patients with these host risk factors such as the elderly, bilateral disease on chest radiography, or malignancy, or lymphocytopenia. 相似文献114.
Bin Jiao Xiaoyan Liu Lin Zhou Maggie Haitian Wang Yafang Zhou Tingting Xiao Weiwei Zhang Rui Sun Mary Miu Yee Waye Beisha Tang Lu Shen 《PloS one》2015,10(12)
Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD. Risk SNPs included rs9331888 (CLU), rs6691117 (CR1), rs4938933 (MS4A), rs9349407 (CD2AP), rs1160985 (TOMM40), rs4945261 (GAB2) and rs5984894 (PCDH11X); Protective SNPs consisted of rs744373 (BIN1), rs1562990 (MS4A), rs597668 (EXOC3L2), rs9271192 (HLA-DRB5/DRB1), rs157581 and rs11556505 (TOMM40). Among positive SNPs presented above, we found the interaction between rs4938933 (risk) and rs1562990 (protective) in MS4A weakened their each effect for LOAD; for three significant SNPs in TOMM40, their cumulative interaction induced the two protective SNPs effects lost and made the risk SNP effect aggravate for LOAD. Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk. In a word, our study indicates that SNP-SNP interaction existed in the same gene or cross different genes, which could weaken or aggravate their initial single effects for LOAD. 相似文献
115.
A Comparison of Some Organizational Characteristics of the Mouse Central Retina and the Human Macula
Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident. 相似文献
116.
117.
Robert Fitzgerald Breann DeSantiago Danielle Y. Lee Guangdong Yang Jae Yeon Kim D. Brian Foster Yee Chan-Li Maureen R. Horton Reynold A. Panettieri Rui Wang Steven S. An 《Biochemical and biophysical research communications》2014
Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)–the end effector of acute airway narrowing in asthma. Using magnetic twisting cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1–10 mM). GYY4137 slowly released appreciable levels of H2S in the range of 10–275 μM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24 h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease. 相似文献
118.
Dayanidhi Sarkar Masahiro Yabusaki Yuta Hasebe Pei Yee Ho Shuji Kohmoto Takayuki Kaga Kazuyuki Shimizu 《Applied microbiology and biotechnology》2010,87(1):127-136
The metabolism of Gluconacetobacter oboediens was investigated in relation to different carbon sources for the continuous cultures at the dilution rate of 0.05 h−1. The 13C-flux result implies the formation of metabolic recycles for the case of using glucose and acetate as carbon sources. When
glucose and ethanol were used as carbon sources, the specific ethanol uptake rate and the specific acetate production rate
increased as the feed ethanol concentration was increased from 40 to 60 g/l, while the specific CO2 production rate and the biomass concentration decreased, where the 13C-metabolic flux result indicates that the glycolysis, oxidative PP pathway, and the tricarboxylic acid (TCA) cycle were less
active, resulting in less biomass concentration. The flux result also implies that oxaloacetate decarboxylase flux became
negative, so that oxaloacetate is backed up by this pathway, resulting in less activity of glyoxylate pathway. When gluconate
was added for the case of using glucose and ethanol as carbon sources, the acetate and cell concentrations as well as gluconate
concentrations increased. The glucose and ethanol concentrations decreased concomitantly with the increased feed gluconate
concentration. In accordance with these fermentation characteristics, the enzyme activity result indicates that glucose dehydrogenase
and glucose-6-phosphate dehydrogenase pathways became less active, while the glycolysis and the TCA cycle was activated as
the feed gluconate concentration was increased. 相似文献
119.
Background
Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes. 相似文献120.
Lachlan H. Yee Vibeke Aagaard Angela Johnstone Matthew Lee Staffan J. Kjelleberg Mike Manefield 《Biodegradation》2010,21(6):947-956
The biodegradation of chlorinated organics in vadose zone soils is challenging owing to the presence of oxygen, which inhibits
reductive dehalogenation reactions and consequently the growth of dehalorespiring microbes. In addition, the hydraulic conductivity
of vadose zone soils is typically high, hence attempts to remediate such zones with biostimulation solutions are often unsuccessful
due to the short residence times for these solutions to act upon the native bacterial community. In this study we have identified
sodium alginate as a hydrogel polymer that can be used to increase the residence time of a nutrient solution in an unsaturated
sandy soil. Additionally we have identified neutral red as a redox active compound that can catalyse the reductive dechlorination
of the chlorinated organic hexachloro-1,3-butadiene by activated sludge fed with lactate and acetate. Finally we have shown
that a nutrient solution amended with neutral red and sodium alginate can lower the redox potential and reduce hexachloro-1,3-butadiene
concentrations in a contaminated vadose zone soil. 相似文献