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61.
Balázs Rada 《FEBS letters》2010,584(5):917-881
Hydrogen peroxide production by the NADPH oxidase Duox1 occurs during activation of respiratory epithelial cells stimulated by purified bacterial ligands, such as lipopolysaccharide. Here, we characterize Duox activation using intact bacterial cells of several airway pathogens. We found that only Pseudomonas aeruginosa, not Burkholderia cepacia or Staphylococcus aureus, triggers H2O2 production in bronchial epithelial cells in a calcium-dependent but predominantly ATP-independent manner. Moreover, by comparing mutant Pseudomonas strains, we identify several virulence factors that participate in Duox activation, including the type-three secretion system. These data provide insight on Duox activation by mechanisms unique to P. aeruginosa. 相似文献
62.
《MABS-AUSTIN》2013,5(5):919-929
ABSTRACTMultivalent mono- or bispecific antibodies are of increasing interest for therapeutic applications, such as efficient receptor clustering and activation, or dual targeting approaches. Here, we present a novel platform for the generation of Ig-like molecules, designated diabody-Ig (Db-Ig). The antigen-binding site of Db-Ig is composed of a diabody in the VH-VL orientation stabilized by fusion to antibody-derived homo- or heterodimerization domains, e.g., CH1/CL or the heavy chain domain 2 of IgE (EHD2) or IgM (MHD2), further fused to an Fc region. In this study, we applied the Db-Ig format for the generation of tetravalent bispecific antibodies (2 + 2) directed against EGFR and HER3 and utilizing different dimerization domains. These Db-Ig antibodies retained the binding properties of the parental antibodies and demonstrated unhindered simultaneous binding of both antigens. The Db-Ig antibodies could be purified by a single affinity chromatography resulting in a homogenous preparation. Furthermore, the Db-Igs were highly stable in human plasma. Importantly, only one short peptide linker (5 aa) per chain is required to generate a Db-Ig molecule, reducing the potential risk of immunogenicity. The presence of a fully functional Fc resulted in IgG-like pharmacokinetic profiles of the Db-Ig molecules. Besides tetravalent bispecific molecules, this modular platform technology further allows for the generation of other multivalent molecules of varying specificity and valency, including mono-, bi-, tri- and tetra-specific molecules, and thus should be suitable for numerous applications. 相似文献
63.
The effect of mutual shading on the root/shoot ratio and on the number of nodal roots of maize was studied. Plants of two varieties (Dea and LG2281) were grown in individual pots of 9 L, at three plant densities: 7.5, 11 and 15 plants m–2. A control experiment was carried out in order to study if root growth was affected by the small size of the pots. Maize plants (cv Dea) were grown at a low plant density (7.5 plants m–2) in pots of two different volumes (9 and 25 L respectively). In both experiments plants were watered every two hours with a nutrient solution. Some plants were sampled at five dates in the main experiment and the following data were recorded: foliar stage; root, stem and leaf dry weight; number of root primordia and number of emerged roots per phytomer. The final sampling date occurred at silking.Results of the control experiment showed that the root biomass was lower in small pots but the number of nodal roots per phytomer was not affected.Results of the main experiment showed that the total plant biomass and the root/shoot ratio were lower at high plant density. The number of emerged roots was strongly reduced on the upper phytomer (P8). This reduction was mainly due to a lower percentage of root primordia which elongated. A proposed interpretation is that the number of roots which emerge on upper phytomers is controlled by carbohydrate availability. 相似文献
64.
Valerio Capraro Giorgia Cococcioni 《Proceedings. Biological sciences / The Royal Society》2015,282(1811)
Recent studies suggest that cooperative decision-making in one-shot interactions is a history-dependent dynamic process: promoting intuition versus deliberation typically has a positive effect on cooperation (dynamism) among people living in a cooperative setting and with no previous experience in economic games on cooperation (history dependence). Here, we report on a laboratory experiment exploring how these findings transfer to a non-cooperative setting. We find two major results: (i) promoting intuition versus deliberation has no effect on cooperative behaviour among inexperienced subjects living in a non-cooperative setting; (ii) experienced subjects cooperate more than inexperienced subjects, but only under time pressure. These results suggest that cooperation is a learning process, rather than an instinctive impulse or a self-controlled choice, and that experience operates primarily via the channel of intuition. Our findings shed further light on the cognitive basis of human cooperative decision-making and provide further support for the recently proposed social heuristics hypothesis. 相似文献
65.
A new species of Bucklandia is described based on a permineralized fossil trunk that was obtained from sediments of Upper Cretaceous age from Hokkaido, Japan. The quality of preservation is exquisite, and anatomical and morphological features are preserved at the cellular level. The specimen is clearly bennettitalean because of the cycadeoidean-type arrangement of vascular bundles in the petiole. However, this specimen is unique among previously described progymnosperms and gymnosperms in possessing a unilacunar five-trace type of nodal structure. The fossil thus contributes to a more complete understanding of the variation of nodal structure in bennettitalean trunks. 相似文献
66.
Weber W Marty RR Keller B Rimann M Kramer BP Fussenegger M 《Biotechnology and bioengineering》2002,80(6):691-705
The novel macrolide-inducible and -repressible mammalian gene regulation systems (E.REX) have been cloned into a variety of sophisticated expression configurations including (1) multi-purpose expression vectors, (2) pTRIDENT-based artificial operons, (3) dual-regulated expression strategies for independent control of two different transgenes, (4) autoregulated vectors for one-step installation of adjustable multigene expression, and (5) oncoretroviral and lentiviral plasmids for transduction of macrolide-, streptogramin- and tetracycline-dependent transactivators and production of cell lines supporting independent control of three different transgenes. This vector portfolio represents a construction kit-like toolbox for efficient installation of adjustable gene expression responsive to clinically licensed antibiotics and enables the design of multiregulated multigene metabolic engineering strategies required for biopharmaceutical manufacturing, gene therapy, and tissue engineering. 相似文献
67.
68.
Time‐resolved fluorometry of lanthanide chelates is one of the most useful non‐isotopic detection techniques and has been used in numerous applications in biomedical science. We developed a time‐resolved fluoroimmunoassay (TRFIA) to quantify α‐fetoprotein (AFP) and hepatitis B virus surface antigen (HBsAg) in human serum. Based on a two‐site sandwich protocol, monoclonal antibodies (McAbs) against AFP and HBsAg were co‐coated in 96 microtitration wells and tracer McAbs against HBsAg and AFP were labeled with europium (Eu) and samarium (Sm) chelates, respectively. After application of diluted serum samples, Eu3+‐ and Sm3+‐McAbs were added and fluorescence signals of Sm3+ and Eu3+ tracers were collected. Detection limits of AFP and HBsAg were 0.09 mIU/L and 0.01 µg/L, respectively. Measurement ranges of AFP‐TRFIA and HBsAg‐TRFIA were 1–1000 mIU/L and 0.2‐150 µg/L, respectively. Intra‐ and inter‐assay coefficients of variation of AFP‐TRFIA were 3.3‐4.1% and 5.7‐7.2% and for HBsAg‐TRFIA were 2.9‐3.9% and 4.9‐6.8%, respectively. Linear correlation of TRFIA and chemiluminescence immunoassay measurements resulted in a correlation coefficient of 0.9949 for AFP and 0.9940 for HBsAg. For the endurance test, Eu‐labeled McAbs were stable for at least one year at ?20°C and the results of the TRFIA with the same reagents were also reproducible after one year. The availability of a highly sensitive, reliable and convenient AFP/HBsAg TRFIA will allow the quantification of both AFP and HBsAg, thereby providing diagnostic value in various clinical conditions and could be applied for clinical use. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
69.
Wen Gao Ying Xu Jianxiang Liu Xiaolei Wang Xinhong Dong Guigen Teng Binbin Liu Jinpei Dong Chaoyi Ge Hui Ye Xuezhi Zhang Hong Cheng 《Helicobacter》2023,28(2):e12947
Background
The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin.Objective
To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.Design
Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing.Results
A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline.Conclusions
For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin. 相似文献70.
Our previous studies indicate that phosphatidylinositol 4-kinase IIα can promote the growth of multi-malignant tumors viaHER-2/PI3K andMAPK pathways.However, the molecular mechanisms of this pathway and its potential for clinical application remain unknown. In this study, we found that PI4KIIα could be an ideal combinatorial target for EGFR treatment via regulating EGFR degradation. Results showed that PI4KIIα knockdown reduced EGFR protein level, and the expression ofPI4KIIα shows a strong correlation with EGFR in human breast cancer tissues (r = 0.77, P<0.01). PI4KIIα knockdown greatly prolonged the effects and decreased the effective dosage ofAG-1478, a specific inhibitor of EGFR. In addition, it significantly enhanced AG1478-induced inhibition of tumor cell survival and strengthened the effect of the EGFR-targeting anti-cancer drug Iressa in xenograft tumor models. Mechanistically, we found that PI4KIIα suppression increased EGFR ligand-independent degradation. Quantitative proteomic analysis by stable isotope labeling with amino acids in cell culture (SILAC) and LC-MS/MS suggested that HSP90mediated the effect of PI4KIIα onEGFR. Furthermore, we found that combined inhibition of PI4KIIα and EGFR suppressed both PI3K/AKT and MAPK/ERK pathways, and resulted in downregulation of multiple oncogenes like PRDX2, FASN, MTA2, ultimately leading to suppression of tumor growth. Therefore,we conclude that combined inhibition of PI4KIIα and EGFR exerts a multiple anti-tumor effect. Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIIα presents anovel strategy tocombatEGFR-dependent tumors. 相似文献