Publications

from gene to harvest: insights into upstream process development for the gmp production of a monoclonal antibody in transgenic tobacco plants.	the eu sixth framework programme integrated project 'pharma-planta' developed an approved manufacturing process for recombinant plant-made pharmaceutical proteins (pmps) using the human hiv-neutralizing monoclonal antibody 2g12 as a case study. in contrast to the well-established chinese hamster ovary platform, which has been used for the production of therapeutic antibodies for nearly 30 years, only draft regulations were initially available covering the production of recombinant proteins in tr ...	2015	26214282
intravenously administered recombinant human type vii collagen derived from chinese hamster ovary cells reverses the disease phenotype in recessive dystrophic epidermolysis bullosa mice.	recessive dystrophic epidermolysis bullosa (rdeb) is an inherited disorder characterized by skin fragility, blistering, and multiple skin wounds with no currently approved or consistently effective treatment. it is due to mutations in the gene encoding type vii collagen (c7). using recombinant human c7 (rhc7) purified from human dermal fibroblasts (fb-rhc7), we showed previously that intravenously injected rhc7 distributed to engrafted rdeb skin, incorporated into its dermal-epidermal junction ( ...	2015	26203639
phase 1 safety, tolerability, and pharmacokinetic study of single ascending doses of xm17 (recombinant human follicle-stimulating hormone) in downregulated healthy women.	xm17 is a recombinant human follicle-stimulating hormone (follitropin alfa) for stimulation of multifollicular development in women undergoing controlled ovarian hyper-stimulation during assisted reproductive therapy and for treatment of anovulation. manufactured using chinese hamster ovary cells transfected with the human follicle-stimulating hormone gene, xm17 has an identical amino acid sequence to that of the human protein as well as to those of the other approved recombinant human follicle- ...	2015	26213478
automatic cell detection in bright-field microscopy for microbeam irradiation studies.	automatic cell detection in bright-field illumination microscopy is challenging due to cells' inherent optical properties. applications including individual cell microbeam irradiation demand minimisation of additional cell stressing factors, so contrast-enhancing fluorescence microscopy should be avoided. additionally, the use of optically non-homogeneous substrates amplifies the problem. this research focuses on the design of a method for automatic cell detection on polypropylene substrate, sui ...	2015	26236995
trace levels of the cho host cell protease cathepsin d caused particle formation in a monoclonal antibody product.	chinese hamster ovary (cho) cells are often used to produce therapeutic monoclonal antibodies (mabs). cho cells express many host cell proteins (hcps) required for their growth. interactions of hcps with mabs can sometimes result in co-purification of trace levels of 'hitchhiker' hcps during the manufacturing process. purified mab-1 product produced in early stages of process optimization had high hcp levels. in addition, these lots formed delayed-onset particles containing mab-1 and its heavy c ...	2015	26259961
prophylactic and postexposure efficacy of a potent human monoclonal antibody against mers coronavirus.	middle east respiratory syndrome (mers) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (cov), likely transmitted to humans by infected camels. there is no licensed vaccine or antiviral for mers, therefore new prophylactic and therapeutic strategies to combat human infections are needed. in this study, we describe, for the first time, to our knowledge, the isolation of a potent mers-cov-neutralizing antibody from memory b cells of an infected individual. th ...	2015	26216974
interaction of propofol with voltage-gated human kv1.5 channel through specific amino acids within the pore region.	the intravenous anesthetic propofol affects the function of a diversity of ligand-gated and voltage-gated ion channels. however, there is little information as to whether propofol directly interacts with voltage-gated ion channel proteins to modulate their functions. the kv1.5 channel is activated by membrane depolarization during action potentials and contributes to atrial repolarization in the human heart. this study was undertaken to examine the effect of propofol on voltage-gated human kv1.5 ...	2015	26256861
construction of a luciferase reporter system to monitor osteogenic differentiation of mesenchymal stem cells by using a mammalian artificial chromosome vector.	mesenchymal stem cells (mscs) hold promise for application in adult stem cell-mediated regenerative medicine in bone remodeling and fracture repair. mscs in vitro can be directed to osteogenic lineage by dexamethasone (dex); however, the use of dex is not practical in clinical settings because of adverse side effects such as glucocorticoid-induced osteoporosis. for identifying substances that facilitate osteogenesis, a monitoring system, which detects the osteogenic differentiation stage of mscs ...	2015	26190894
a global rna-seq-driven analysis of cho host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.	boehringer ingelheim uses two cho-dg44 lines for manufacturing biotherapeutics, bi-hex-1 and bi-hex-2, which produce distinct cell type-specific antibody glycosylation patterns. a recently established cho-k1 descended host, bi-hex-k1, generates antibodies with glycosylation profiles differing from cho-dg44. manufacturing process development is significantly influenced by these unique profiles. to investigate the underlying glycosylation related gene expression, we leveraged our cho host and prod ...	2015	26212696
very high cell density perfusion of cho cells anchored in a non-woven matrix-based bioreactor.	recombinant chinese hamster ovary (cho) cells producing igg monoclonal antibody were cultivated in a novel perfusion culture system celltank, integrating the bioreactor and the cell retention function. in this system, the cells were harbored in a non-woven polyester matrix perfused by the culture medium and immersed in a reservoir. although adapted to suspension, the cho cells stayed entrapped in the matrix. the cell-free medium was efficiently circulated from the reservoir into- and through the ...	2015	26211737
generation and characterization of a monoclonal antibody against canine tissue factor.	tissue factor (tf, coagulation factor iii) has recently identified roles in innate immunity and cancer. we generated a murine mab against canine tf (ctf) cloned from madin-darby canine kidney cells and expressed in chinese hamster ovarian (cho) cells, with an equine il-4 tag. one clone was selected for purification based on initial screening of cho cell supernatants. the mab was further characterized with flow cytometry, immunofluorescent microscopy, immunoblotting and immunohistochemical staini ...	2015	26187440
chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development.	basal medium design is considered one of the most important steps in process development. to optimize chemically defined (cd) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing chinese hamster ovary (cho) cell lines. in the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. in the next step, these groups were optimized by spent med ...	2015	26183860
mathematical models describing chinese hamster ovary cell death due to electroporation in vitro.	electroporation is a phenomenon used in the treatment of tumors by electrochemotherapy, non-thermal ablation with irreversible electroporation, and gene therapy. when treating patients, either predefined or variable electrode geometry is used. optimal pulse parameters are predetermined for predefined electrode geometry, while they must be calculated for each specific case for variable electrode geometry. the position and number of electrodes are also determined for each patient. it is currently ...	2015	26223863
effects of peptone supplementation in different culture media on growth, metabolic pathway and productivity of cho dg44 cells; a new insight into amino acid profiles.	the optimization of bioprocess conditions towards improved growth profile and productivity yield is considered of great importance in biopharmaceutical manufacturing. peptones as efficient sources of nutrients have been studied for their effect on media development; however, their role on metabolic pathway is not well understood.	2015	26232332
upper limit of magnetic effect on α/β ratio.	magnetic resonance imaging (mri) is being integrated into radiotherapy delivery for mri-guided radiotherapy. the purpose of this work is to investigate theoretically the upper limit of any potential magnetic effect on the α/β ratio, an important radiobiological parameter in radiation therapy. based on the theory of dual radiation action, the α/β ratio can be expressed by an integral of the product of two microdosimetry quantities (x) and t(x), where (x) is the probability that two energy transfe ...	2015	26301729
engineered cho cells for production of diverse, homogeneous glycoproteins.	production of glycoprotein therapeutics in chinese hamster ovary (cho) cells is limited by the cells' generic capacity for n-glycosylation, and production of glycoproteins with desirable homogeneous glycoforms remains a challenge. we conducted a comprehensive knockout screen of glycosyltransferase genes controlling n-glycosylation in cho cells and constructed a design matrix that facilitates the generation of desired glycosylation, such as human-like α2,6-linked sialic acid capping. this enginee ...	2015	26192319
role of complement receptor 1 (cr1; cd35) on epithelial cells: a model for understanding complement-mediated damage in the kidney.	the regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of c3 activation. complement receptor 1 (cr1) is the most versatile of these inhibitors with both receptor and regulatory functions. while expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. its expression by this cell population has aroused considerable speculation as to i ...	2015	26260209
compartment-specific metabolomics for cho reveals that atp pools in mitochondria are much lower than in cytosol.	mammalian cells show a compartmented metabolism. getting access to subcellular metabolite pools is of high interest to understand the cells' metabolomic state. therefore a protocol is developed and applied for monitoring compartment-specific metabolite and nucleotide pool sizes in chinese hamster ovary (cho) cells. the approach consists of a subtracting filtering method separating cytosolic components from physically intact mitochondrial compartments. the internal standards glucose-6-phosphate a ...	2015	26179617
overexpressed calponin3 by subsonic vibration induces neural differentiation of huc-mscs by regulating the ionotropic glutamate receptor.	in this study, we used proteomics to investigate the effects of sonic vibration (sv) on mesenchymal stem cells derived from human umbilical cords (huc-mscs) during neural differentiation to understand how sv enhances neural differentiation of huc-mscs. we investigated the levels of gene and protein related to neural differentiation after 3 or 5 days in a group treated with 40-hz sv. in addition, protein expression patterns were compared between the control and the 40-hz sv-treated huc-msc groups ...	2015	26175098
regulation of pro-apoptotic phosphorylation of kv2.1 k+ channels.	caspase activity during apoptosis is inhibited by physiological concentrations of intracellular k+. to enable apoptosis in injured cortical and hippocampal neurons, cellular loss of this cation is facilitated by the insertion of kv2.1 k+ channels into the plasma membrane via a zn2+/camkii/snare-dependent process. pro-apoptotic membrane insertion of kv2.1 requires the dual phosphorylation of the channel by src and p38 at cytoplasmic n- and c-terminal residues y124 and s800, respectively. in this ...	2015	26115091
[effect of the integrin β3 cytoplasmic nity motif on α ii bβ3-mediated cell functions in cho cell model].	objlective: to investigate the effect of integrin β3 cytoplasmic nity motif on αiibβ3-mediated cell functions.	2015	26117034
advanced process monitoring and feedback control to enhance cell culture process production and robustness.	it is a common practice in biotherapeutic manufacturing to define a fixed-volume feed strategy for nutrient feeds, based on historical cell demand. however, once the feed volumes are defined, they are inflexible to batch-to-batch variations in cell growth and physiology and can lead to inconsistent productivity and product quality. in an effort to control critical quality attributes and to apply process analytical technology (pat), a fully automated cell culture feedback control system has been ...	2015	26108810
characterisation of hepcidin response to holotransferrin treatment in cho trvb-1 cells.	iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. to understand the role of transferrin receptor (tfr) and intracellular iron in hepcidin secretion, chinese hamster ovary transferrin receptor variant (cho trvb-1) cells were used that express iron-response-element-depleted human tfrc mrna (tfrc∆ire). results showed that cho trvb-1 cells expressed higher basal levels of cell-surface tfr1 than hepg2 cells (2.2-fold; p < 0.01) and following 5 g/l holo ...	2015	26142326
identification and characterization of the adipokinetic hormone/corazonin-related peptide signaling system in rhodnius prolixus.	the mammalian gonadotropin-releasing hormone is evolutionarily related to the arthropod adipokinetic hormone and the recently discovered adipokinetic hormone/corazonin-related peptide (acp). the function of the acp signaling system in arthropods is currently unknown. in the present study, we identify and characterize the acp signaling system in the kissing bug rhodnius prolixus. we isolated the complete cdna sequence encoding r. prolixus acp (rhopr-acp) and examined its expression pattern. rhopr ...	2015	26138617
differential thermosensitivity in mixed syndrome cardiac sodium channel mutants.	cardiac arrhythmias are often associated with mutations in scn5a the gene that encodes the cardiac paralogue of the voltage-gated sodium channel, nav 1.5. the nav 1.5 mutants r1193q and e1784k give rise to both long qt and brugada syndromes. various environmental factors, including temperature, may unmask arrhythmia. we sought to determine whether temperature might be an arrhythmogenic trigger in these two mixed syndrome mutants. whole-cell patch clamp was used to measure the biophysical propert ...	2015	26131924
n-acetylcysteine protects chinese hamster ovary cells from oxidative injury and apoptosis induced by microcystin-lr.	this study aimed to investigate the mc-lr induced oxidative injury and apoptosis in chinese hamster ovary (cho) cells, and the protective effects of n-acetylcysteine (nac) on these cells. cell viability was determined by mtt assay after exposure to nac at various concentrations (0, 1, 5, 10, 20, 30, 40, 50, 60 and 80 mmol/l) alone, or nac (0, 1 and 5 mmol/l) plus mc-lr (0, 2.5, 5 and 10 μg/ml) for 24 h. the reactive oxygen species (ros) in cho cells were measured by dcfh-da, mitochondrial membra ...	2015	26131064
spag6 negatively regulates neuronal migration during mouse brain development.	sperm-associated antigen 6 (spag6) is a chlamydomonas reinhardtii pf16 homologous gene detected in the human testis and is crucial for sperm motility. neuronal migration is a dynamic process requiring coordinated cytoskeletal remodeling, and spag6 is co-localized with microtubules in chinese hamster ovary cells and cos-1 cells. however, the role of spag6 in neuronal migration remains unclear. here, we demonstrated that spag6 was continuously expressed in the developing cerebral cortex. using in ...	2015	26130477
integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by cho cells.	based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of chinese hamster ovary (cho) cells to produce a model "difficult-to-express" homodimeric fc-fusion protein, sp35fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. as expression of sp35fc induced an unfolded protein response in transfected host cells, w ...	2015	26126657
regulating effects of insertion direction of matrix attachment regions on transgenic expression in stably transformed chinese hamster ovary cells.	we investigated the effects of different directions of insertion of matrix attachment region (mar) sequences on transgenic expression in stably transformed chinese hamster ovary (cho) cells. the mar sequences were inserted in forward or reverse directions into the expression vectors, and transfected into cho cells. the expression of the chloramphenicol acetyltransferase (cat) reporter gene and the relative copy numbers of the cat gene were analyzed. the cat gene expression levels in the vector w ...	2015	26125912
hypolipidemic effect of safflower yellow and primary mechanism analysis.	we examined the hypolipidemic effect of safflower yellow (sy) on hyperlipidemic mice and its influence on the biological synthesis of cholesterol in cells. over 4 weeks, the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in serum were detected using a kit; mouse liver samples were acquired for paraffin sections, and mouse liver cells were observed under light microscope. chinese hamster ovary cells were cultured in vitro, ...	2015	26125829
a role for homologous recombination proteins in cell cycle regulation.	eukaryotic cells respond to dna breaks, especially double-stranded breaks (dsbs), by activating the dna damage response (ddr), which encompasses dna repair and cell cycle checkpoint signaling. the dna damage signal is transmitted to the checkpoint machinery by a network of specialized dna damage-recognizing and signal-transducing molecules. however, recent evidence suggests that dna repair proteins themselves may also directly contribute to the checkpoint control. here, we investigated the role ...	2015	26125600
cytotoxic and genotoxic effects of abamectin, chlorfenapyr, and imidacloprid on chok1 cells.	the cytotoxicity and genotoxicity of abamectin, chlorfenapyr, and imidacloprid have been evaluated on the chinese hamster ovary (chok1) cells. neutral red incorporation (nri), total cellular protein content (tcp), and methyl tetrazolium (mtt) assays were followed to estimate the mid-point cytotoxicity values, nri50, tcp50, and mtt50, respectively. the effects of the sublethal concentration (nri25) on glutathione s-transferase (gst), glutathione reductase (grd), glutathione peroxidase (gpx), and ...	2015	26122579
an automated rna-seq analysis pipeline to identify and visualize differentially expressed genes and pathways in cho cells.	recent advances in rna-seq based comparative transcriptomics have opened up a unique opportunity to understand the mechanisms of different phenotypes in bioprocessing-related cell lines including chinese hamster ovary (cho) cells. however, simple and powerful tools are needed to translate large data sets into biologically relevant information that can be leveraged for genetic engineering and cell culture medium and process development. while tools exist to perform specific tasks associated with ...	2015	26150012
culture temperature modulates monoclonal antibody charge variation distribution in chinese hamster ovary cell cultures.	to investigate the effect of lowering culture temperature on monoclonal antibody charge variation distribution in chinese hamster ovary cell cultures.	2015	26149578
changes in intracellular atp-content of cho cells as response to hyperosmolality.	a variety of approaches has been published to enhance specific productivity (qp) of recombinant chinese hamster ovary (cho) cells. changes in culture conditions, e. g. temperature shifts, sodium butyrate treatment and hyperosmolality, were shown to improve qp . to contribute to a better understanding of the correlation between hyperosmolality and enhanced qp , we analyzed cellular kinetics and intracellular adenine nucleotide pools during osmotic shift periods. known phenotypes like increased fo ...	2015	26146937
comparison of five different in vitro assays for assessment of sodium metavanadate cytotoxicity in chinese hamster ovary cells (cho-k1 line).	this investigation was undertaken to compare five different in vitro cytotoxicity assays for their power in revealing vanadium-mediated toxicity in chinese hamster ovary (cho)-k1 cells. the cells were exposed to sodium metavanadate (navo(3)) in the range of 10-1000 µm for 24 h and thereafter the cytotoxic effects of navo(3) were measured by colorimetric in vitro assays: the neutral red (nr) test, the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2h-tetrazolium-5-carboxyanilide inner salt (xtt) assay, ...	2015	23524879
production of stable bispecific igg1 by controlled fab-arm exchange: scalability from bench to large-scale manufacturing by application of standard approaches.	the manufacturing of bispecific antibodies can be challenging for a variety of reasons. for example, protein expression problems, stability issues, or the use of non-standard approaches for manufacturing can result in poor yield or poor facility fit. in this paper, we demonstrate the use of standard antibody platforms for large-scale manufacturing of bispecific igg1 by controlled fab-arm exchange. two parental antibodies that each contain a single matched point mutation in the ch3 region were se ...	2015	23995617
[a novel human bone morphogenetic protein-7 variant with an enriched heparin-binding site].	bmps are osteoinductive proteins which are used in treatment of acute fractures. large quantities of recombinant proteins are usually needed to achieve efficacy in the clinic. this translates to severe complications and high costs. different strategies have been developed to improve the efficacy and safety of bmps. modification of the heparin-binding site in order to increase the local retention time of the morphogen is one of these approaches. aiming at further improvement in properties of bmp- ...	2015	23888776
galactosylation variations in marketed therapeutic antibodies.	there are currently ~25 recombinant full-length iggs (riggs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. most of these are based on igg1k framework and are either chimeric, humanized or human antibodies manufactured using either chinese hamster ovary (cho) cells or mouse myeloma cells as the expression system. because cho and mouse myeloma cells are mammalian cells, riggs produced in these cell lines are typically n-glycosylate ...	2015	22531450
evaluation of the toxic activity of anorectic diethylpropion in chinese hamster ovary cells.	diethylpropion has been available in the market for treating obesity for over 50 years. refined studies are lacking to fully elucidate its action spectrum. the aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in chinese hamster ovary (cho) cells. comet assay (detects breaks in the dna strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. in comet assay, we fo ...	2015	25005806
in vitro biological characterization of ifn-β-1a major glycoforms.	recombinant human interferon β-1a (ifn-β-1a) is extensively used as the first-line treatment of relapsing forms of multiple sclerosis. its glycosylation is recognized as having a complex impact on a wide range of molecule characteristics and functions. the present study reports the enrichment of ifn-β-1a glycoforms and their physicochemical and biological characterization by means of electrospray ionization-mass spectrometry, sialic acid content, thermal denaturation and various in vitro bioassa ...	2015	25117008
mutagenicity and clastogenicity evaluation of metaphenoxy benzyl chloride by ames and micronucleus assays.	metaphenoxy benzyl chloride (3-pbc; cas # 53874-66-1) is a commonly used intermediate in organic synthesis and is a widely used chemical building block. there is likelihood of human contact with 3-pbc in the process of organic or pesticide synthesis and even through as impurity in the product. further, this chemical has been reported to be found in water reservoirs causing a threat to aqueous flaura and fauna. genotoxic alert has been suspected for the chemical 3-pbc based on its structure hence ...	2015	25109298
characterization of the effects of cl⁻ channel modulators on tmem16a and bestrophin-1 ca²⁺ activated cl⁻ channels.	the ca(2+) activated cl(-) channels (caccs) play a multitude of important physiological functions. a number of candidate proteins have been proposed to form cacc, but only two families, the bestrophins and the tmem16 proteins, recapitulate the properties of native cacc in expression systems. studies of endogenous caccs are hindered by the lack of specific pharmacology as most cl(-) channel modulators lack selectivity and a systematic comparison of the effects of these modulators on tmem16a and b ...	2015	25078708
rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions.	high viscosity of monoclonal antibody formulations at concentrations ≥100 mg/ml can impede their development as products suitable for subcutaneous delivery. the effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of mab 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. the mutations were designed to reduce viscosity by disrupting either an aggregation prone region (apr), which also participates i ...	2015	25559441
bafilomycin l, a new inhibitor of cholesteryl ester synthesis in mammalian cells, produced by marine-derived streptomyces sp. opma00072.	marine-derived streptomyces sp. opma00072 was found to produce inhibitors of the synthesis of neutral lipids in a cell-based assay using chinese hamster ovary (cho) cells. a new 16-membered macrolide named bafilomycin l (bfl) (1) was isolated along with the known structurally related bafilomycin c1 (bfc1) (3) from the culture broth of the actinomycete by solvent extraction, octadecylsilyl column chromatography and hplc. bfl inhibited cholesteryl ester (ce) synthesis in cho cells with an ic50 val ...	2015	25095804
phenylarsine oxide as a redox modulator of transient receptor potential vanilloid type 1 channel function.	transient receptor potential vanilloid type 1 (trpv1) channels are capable of detecting and integrating noxious stimuli and play an important role in nociceptor activation and sensitization. it has been demonstrated that oxidizing agents are capable of positively modulating (sensitizing) the trpv1 channel. the present study investigates the ability of the thiol-oxidizing agent phenylarsine oxide (pao) to modulate trpv1 currents under voltage-clamp conditions. we assessed the ability of pao to mo ...	2015	25250537
design of serum-free medium for suspension culture of cho cells on the basis of general commercial media.	the design of serum-free media for suspension culture of genetically engineered chinese hamster ovary (cho) cells using general commercial media as a basis was investigated. subcultivation using a commercial serum-free medium containing insulin-like growth factor (igf)-1 with or without fcs necessitated additives other than igf-1 to compensate for the lack of fcs and improve cell growth. suspension culture with media containing several combinations of growth factors suggested the effectiveness o ...	2015	25149286
protective effects of ascorbic acid against the genetic and epigenetic alterations induced by 3,5-dimethylaminophenol in aa8 cells.	exposure to monocyclic aromatic alkylanilines (maas), namely 2,6-dimethylaniline (2,6-dma), 3,5-dimethylaniline (3,5-dma) and 3-ethylaniline (3-ea), was significantly and independently associated with bladder cancer incidence. 3,5-dmap (3,5-dimethylaminophenol), a metabolite of 3,5-dma, was shown to induce an imbalance in cytotoxicity cellular antioxidant/oxidant status, and dna damage in mammalian cell lines. this study was designed to evaluate the protective effect of ascorbic acid (asc) again ...	2015	25178734
monitoring change in refractive index of cytosol of animal cells on affinity surface under osmotic stimulus for label-free measurement of viability.	we demonstrated that a metal-clad waveguide (mcw)-based biosensor can be applied to label-free measurements of viability of adherent animal cells with osmotic stimulation in real time. after chinese hamster ovary (cho) and human embryonic kidney cell 293 (hek293) cells were attached to a concanavalin a (con a)-modified sensor surface, the magnitudes of cell responses to non-isotonic stimulation were compared between live and dead cells. the live cells exhibited a change in the refractive index ( ...	2015	25232665
raloxifene inhibits cloned kv4.3 channels in an estrogen receptor-independent manner.	raloxifene is widely used for the treatment and prevention of postmenopausal osteoporosis. we examined the effects of raloxifene on the kv4.3 currents expressed in chinese hamster ovary (cho) cells using the whole-cell patch-clamp technique and on the long-term modulation of kv4.3 messenger rna (mrna) by real-time pcr analysis. raloxifene decreased the kv4.3 currents with an ic50 of 2.0 μm and accelerated the inactivation and activation kinetics in a concentration-dependent manner. the inhibitor ...	2015	25231973
genotoxicity of 1-methylpyrene and 1-hydroxymethylpyrene in chinese hamster v79-derived cells expressing both human cyp2e1 and sult1a1.	1-methylpyrene (1-mp) is a widespread pollutant that is carcinogenic in animals following metabolic activation. previous studies have shown that benzylic hydroxylation of 1-mp, catalyzed by multiple cyp isoforms, gives rise to 1-hydroxymethylpyrene (1-hmp), which becomes bioreactive following further metabolism by various sulfotransferase (sult) isoforms. however, the mutagenic and chromosome damaging effects of 1-mp and 1-hmp in mammalian cells have not been investigated. in this study a chines ...	2015	25243916
amino acid and glucose metabolism in fed-batch cho cell culture affects antibody production and glycosylation.	fed-batch chinese hamster ovary (cho) cell culture is the most commonly used process for igg production in the biopharmaceutical industry. amino acid and glucose consumption, cell growth, metabolism, antibody titer, and n-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin g (igg) titer and better controlling glycosylation-relat ...	2015	25220616
versatile cellular uptake mediated by catanionic vesicles: simultaneous spontaneous membrane fusion and endocytosis.	lactose-derived catanionic vesicles offer unique opportunities to overcome cellular barriers. these potential nanovectors, very easy to formulate as drug delivery systems, are able to encapsulate drugs of various hydrophilicity. this article highlights versatile interaction mechanisms between these catanionic vesicles, labeled with hydrophilic and amphiphilic fluorescent probes, and a mammalian cell line, chinese hamster ovary. confocal microscopy and flow cytometry techniques show that these ve ...	2015	25310849
fluorescence-based, high-throughput assays for μ-opioid receptor activation using a membrane potential-sensitive dye.	the development of new and improved opioid analgesics requires high-throughput screening (hts) methods to identify potential therapeutics from large libraries of lead compounds. here we describe two simple, real-time fluorescence-based assays of μ-opioid receptor activation that may be scaled up for hts. in att-20 cells expressing the μ-opioid receptor (mopr), opioids activate endogenous g protein gated inwardly rectifying k channels (girk channels), leading to membrane hyperpolarization. in chi ...	2015	25293325
backbone (1)h, (13)c, and (15)n resonance assignments of the fc fragment of human immunoglobulin g glycoprotein.	the fc portion of immunoglobulin g (igg) recruits complements and its cognate receptors, thereby promoting defensive mechanisms in the humoral immune system. these effector functions critically depend on n-glycosylation at the fc region, which is therefore regarded as a crucial factor in the design and production of therapeutic antibodies. nmr spectroscopy plays a unique role in the characterization of conformational dynamics and intermolecular interactions of igg-fc in solutions. here, we repor ...	2015	25291979
bodipy(®) fl histamine as a new modality for quantitative detection of histamine receptor upregulation upon ige sensitization in murine bone marrow-derived mast cells.	flow cytometry is one of the most widely used methods for the qualitative and quantitative analysis of cell surface expressed proteins by making use of fluorescent specific antibodies. lacking an antibody validated for flow cytometry, an alternative approach for labeling cell surface receptors is the use of fluorescently tagged ligands. in this study, histamine h4 receptor transfected chinese hamster ovary cells and murine bone marrow-derived mast cells (mbmmcs) were selected for studying the po ...	2015	25212523
salmeterol's extreme β2 selectivity is due to residues in both extracellular loops and transmembrane domains.	salmeterol is a long-acting β2-agonist, widely used as an inhaled treatment of asthma and chronic obstructive pulmonary disease. it has very high β2-affinity (log kd -8.95) and is very selective for the β2-adrenoceptor (1000-fold selectivity over the β1-adrenoceptor). this study used a mutagenesis approach to determine the exact amino acids in the human β2-adrenoceptor responsible for this very high selectivity. wild-type β2- and β1-adrenoceptors, chimeric β2/β1-adrenoceptors, and receptors with ...	2015	25324048
on dynamically generating relevant elementary flux modes in a metabolic network using optimization.	elementary flux modes (efms) are pathways through a metabolic reaction network that connect external substrates to products. using efms, a metabolic network can be transformed into its macroscopic counterpart, in which the internal metabolites have been eliminated and only external metabolites remain. in efms-based metabolic flux analysis (mfa) experimentally determined external fluxes are used to estimate the flux of each efm. it is in general prohibitive to enumerate all efms for complex netwo ...	2015	25323319
genomic organization and expression of immunoglobulin genes in the chinese hamster (cricetulus griseus).	in science, the hamsters are widely used as a model for studying the human diseases because they display many features like humans. the utility of the chinese hamster as a biology model can be further enhanced by further characterization of the genes encoding components of the immune system. here, we report the genomic organization and expression of the chinese hamster immunoglobulin heavy and light chain genes. the chinese hamster igh locus contains 268 vh segments (132 potentially functional g ...	2015	25271137
the effect of organic anion-transporting polypeptides 1b1, 1b3 and 2b1 on the antitumor activity of flavopiridol in breast cancer cells.	the contribution of organic anion transporting polypeptides (oatps) to the cellular uptake of flavopiridol was investigated in oatp1b1-, oatp1b3- and oatp2b1-expressing chinese hamster ovary (cho) cells. uptake of flavopiridol into these cells showed typical michaelis-menten kinetics with much higher transport capacity for oatp1b3 compared to oatp1b1 and oatp2b1 (vmax/km, 33.9 vs. 8.84 and 2.41 µl/mg/min, respectively). the predominant role of oatps was further supported by a dramatic inhibition ...	2015	25351763
overexpression of serpinb1 in chinese hamster ovary cells increases recombinant igg productivity.	we report the discovery and validation of a novel cho cell engineering target for improving igg expression, serpin peptidase inhibitor, clade b, member 1 (serpinb1). transcriptomic studies using microarrays revealed that serpinb1 was up-regulated in cultures with igg heavy and light chain transcription transiently repressed compared with cultures treated with non-targeting sirna. as proof of concept, a lentiviral vector was employed to overexpress the chinese hamster serpinb1 in a chozn(®) gluta ...	2015	25444873
representative mammalian cell culture test materials for assessment of primary recovery technologies: a rapid method with industrial applicability.	mammalian cell culture material is often difficult to produce accurately and reproducibly for downstream studies. this article presents a methodology for the creation of a set of cell culture test materials where key variables including cell density, cell viability, product, and the host cell protein (hcp) load can be manipulated individually. the methodology was developed using a glutamine synthetase chinese hamster ovary cell line cultured at 5-l and 70-l scales. cell concentration post-cell g ...	2015	25377169
fluorescence techniques used to measure interactions between hydroxyapatite nanoparticles and epidermal growth factor receptors.	the potential applications of nanomaterials in therapeutics are immense and to fully explore this potential, it is important to understand the interaction of nanoparticles with cellular components. to examine the interaction between nanoparticles and cell membrane receptors, this report describes the use of advanced fluorescence techniques to measure interactions between hydroxyapatite (ha) nanoparticles and epidermal growth factor receptors (egfrs), as a model system. fitc-labelled ha nanoparti ...	2015	25367700
a hybrid dielectrophoretic and hydrophoretic microchip for particle sorting using integrated prefocusing and sorting steps.	this work explores dielectrophoresis (dep)-active hydrophoresis in sorting particles and cells. the device consists of prefocusing region and sorting region with great potential to be integrated into advanced lab-on-a-chip bioanalysis devices. particles or cells can be focused in the prefocusing region and then sorted in the sorting region. the dep-active hydrophoretic sorting is not only based on size but also on dielectric properties of the particles or cells of interest without any labelling. ...	2015	25363719
a statistical approach to determining criticality of residual host cell dna.	we propose a method for determining the criticality of residual host cell dna, which is characterized through two attributes, namely the size and amount of residual dna in biopharmaceutical product. by applying a mechanistic modeling approach to the problem, we establish the linkage between residual dna and product safety measured in terms of immunogenicity, oncogenicity, and infectivity. such a link makes it possible to establish acceptable ranges of residual dna size and amount. application of ...	2015	25358029
a cd46-like molecule functional in teleost fish represents an ancestral form of membrane-bound regulators of complement activation.	in the complement system, the regulators of complement activation (rca) play crucial roles in controlling excessive complement activation and in protecting host cell from misdirected attack of complement. several members of rca family have been cloned from cyclostome and bony fish species and classified into soluble and membrane-bound type as in mammalian rca factors. complement-regulatory functions have been described only for soluble rca of lamprey and barred sand bass; however, little is know ...	2015	25452563
global insights into the chinese hamster and cho cell transcriptomes.	transcriptomics is increasingly being used on chinese hamster ovary (cho) cells to unveil physiological insights related to their performance during production processes. the rich transcriptome data can be exploited to provide impetus for systems investigation such as modeling the central carbon metabolism or glycosylation pathways, or even building genome-scale models. to harness the power of transcriptome assays, we assembled and annotated a set of rna-seq data from multiple cho cell lines and ...	2015	25450749
production of bispecific antibodies in "knobs-into-holes" using a cell-free expression system.	bispecific antibodies have emerged in recent years as a promising field of research for therapies in oncology, inflammable diseases, and infectious diseases. their capability of dual target recognition allows for novel therapeutic hypothesis to be tested, where traditional mono-specific antibodies would lack the needed mode of target engagement. among extremely diverse architectures of bispecific antibodies, knobs-into-holes (kihs) technology, which involves engineering ch3 domains to create eit ...	2015	25427258
sialic acids attached to n- and o-glycans within the nav1.4 d1s5-s6 linker contribute to channel gating.	voltage-gated na+ channels (nav) are responsible for the initiation and conduction of neuronal and muscle action potentials. nav gating can be altered by sialic acids attached to channel n-glycans, typically through isoform-specific electrostatic mechanisms.	2015	25450184
titer of trastuzumab produced by a chinese hamster ovary cell line is associated with tricarboxylic acid cycle activity rather than lactate metabolism.	achieving high productivity and quality is the final goal of therapeutic antibody development, but the productivity and quality of antibodies are known to be substantially dependent on the nature of the cell lines expressing the antibodies. we characterized two contrasting cell lines that produce trastuzumab, namely cell line a with a high titer and a low aggregate content and cell line b with a low titer and a high aggregate content to identify the causes of the differences. we observed the fol ...	2015	25449760
structural rearrangements in cho cells after disruption of individual cytoskeletal elements and plasma membrane.	cellular structural integrity is provided primarily by the cytoskeleton, which comprises microtubules, actin filaments, and intermediate filaments. the plasma membrane has been also recognized as a mediator of physical forces, yet its contribution to the structural integrity of the cell as a whole is less clear. in order to investigate the relationship between the plasma membrane and the cytoskeleton, we selectively disrupted the plasma membrane and each of the cytoskeletal elements in chinese h ...	2015	25395197
gpihbp1 missense mutations often cause multimerization of gpihbp1 and thereby prevent lipoprotein lipase binding.	gpihbp1, a gpi-anchored protein of capillary endothelial cells, binds lipoprotein lipase (lpl) in the subendothelial spaces and shuttles it to the capillary lumen. gpihbp1 missense mutations that interfere with lpl binding cause familial chylomicronemia.	2015	25387803
air sparging for prevention of antibody disulfide bond reduction in harvested cho cell culture fluid.	during the scale-up of several chinese hamster ovary (cho) cell monoclonal antibody production processes, significant reduction of the antibody interchain disulfide bonds was observed. the reduction was correlated with excessive mechanical cell shear during the harvest operations. these antibody reduction events resulted in failed product specifications and the subsequent loss of the drug substance batches. several methods were recently developed to prevent antibody reduction, including modifyin ...	2015	25384896
synthesis and evaluation in rats of the dopamine d2/3 receptor agonist 18f-amc20 as a potential radioligand for pet.	dopamine d(2/3) receptor (d(2/3)r) agonist pet tracers are better suited for the imaging of synaptic dopaminergic neurotransmission than d(2/3)r antagonists and may also offer the opportunity to study in vivo the high-affinity state of d(2/3)r (d(2/3)rhigh). with the aim to develop (18)f-labeled d2/3r agonists suitable for widespread clinical application, we report here on the synthesis and in vitro and in vivo evaluation of a d(2/3)r agonist ligand from the aminomethyl chromane (amc) class-(r)- ...	2015	25476538
bryostatin-1 causes radiosensitization of bmg-1 malignant glioma cells through differential activation of protein kinase-cδ not evident in the non-malignant aa8 fibroblasts.	bryostatin-1 (bryo-1), a non-phorbol ester, is known to sensitize mammalian cells against certain chemotherapeutic drugs. we assessed its ability to modify radiation response of mammalian cells using chinese hamster fibroblasts aa8 cells and human malignant glioma bmg-1 cells. in the malignant glioma bmg-1 cell line, bryo-1 pre-treatment significantly enhanced radiation-induced growth inhibition and cytogenetic damage, and further reduced the clonogenic cell survival as compared to cells irradia ...	2015	25472878
effect of temperature shift on levels of acidic charge variants in igg monoclonal antibodies in chinese hamster ovary cell culture.	during the production of therapeutic monoclonal antibodies (mabs), not only enhancement of mab productivity but also control of quality attributes is critical. charge variants, which are among the most important quality attributes, can substantially affect the in vitro and in vivo properties of mabs. during process development for the production of mabs in a chinese hamster ovary cell line, we have observed that an improvement in mab titer is accompanied by an increase in the content of acidic c ...	2015	25466646
biodirected synthesis of miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles.	the recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of delftia sp. strain kcm-006 and their application as antifungal agents and as a drug carrier. transmission electron microscopy (tem) and dynamic light scattering (dls) analysis revealed the formation of spherical and monod ...	2015	25460601
accumulation of carboxy-terminal fragments of app increases phosphodiesterase 8b.	the long-standing "amyloid hypothesis" that alzheimer's disease is caused by the production and aggregation of amyloid-β faces serious challenges by data recently obtained from neuroimaging studies and amyloid-β amyloid-focused clinical trials. meanwhile, accumulation of carboxy-terminal fragments (ctfs) of the amyloid precursor protein (app) may be neurotoxic and may impair synaptic plasticity and long-term memory in alzheimer's disease, as suggested in murine models. to clarify these issues, w ...	2015	25457556
hep-2 cell based indirect immunofluorescence assay for antinuclear antibodies as a potential diagnosis of drug-induced autoimmunity in nonclinical toxicity testing.	antinuclear antibodies (anas) are important biomarkers in the diagnosis of autoimmune diseases in humans; however, the diagnostic performance of ana in nonclinical safety studies are not well understood. here, we studied the use of anas as potential nonclinical biomarkers for drug-induced autoimmunity (dia) using a hep-2 based indirect immunofluorescence assay (ifa). initially, mrl-fas(lpr)/j mice and hgcl₂-treated rats were used as sle-positive models. serum samples obtained from 94 normal mice ...	2015	25455225
gene expression pattern of kifc3 during spermatogenesis of the skink eumeces chinensis.	kinesin superfamily is a class of microtubule-dependent motors that play crucial roles in acrosome biogenesis, nuclear reshaping and flagellum formation during spermiogenesis. we have cloned kinesin-like gene kifc3 (termed ec-kifc3) from the total rna of the testis of the skink eumeces chinensis. the cdna sequence of ec-kifc3 had a full-length of 3033bp, including a 260bp 5'-untranslated region (5'utr), a 445bp 3'-untranslated region (3'utr) and an open reading frame that encoded a 775-amino-aci ...	2015	25434495
canavanine induces insulin release via activation of imidazoline i3 receptors.	the aim of the present study was to identify the effect of canavanine on the imidazoline receptor because canavanine is a guanidinium derivative that has a similar structure to imidazoline receptor ligands. transfected chinese hamster ovary-k1 cells expressing imidazoline receptors (nischarin (nisch)-cho-k1 cells) were used to elucidate the direct effects of canavanine on imidazoline receptors. in addition, the imidazoline i3 receptor has been implicated in stimulation of insulin secretion from ...	2015	25482045
comparison of sybr green and taqman real-time pcr methods for quantitative detection of residual cho host-cell dna in biopharmaceuticals.	the chinese hamster ovary (cho) cell line is one of the predominant hosts used in the bioproduction of pharmaceutical proteins. there have been many concerns about the use of animal cell lines in biopharm industries, and one of the most important concerns has been residual host-cell dna. improper integration of residual dna into the recipient genomes could activate oncogenes or deactivate tumor suppressor genes. real-time polymerase chain reaction (pcr) is a routine assay method used in the quan ...	2015	25481729
association between the xrcc6 polymorphisms and cancer risks: a systematic review and meta-analysis.	a number of studies have been carried out to investigate the association of x-ray repair complementing defective repair in chinese hamster cells 6 (xrcc6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.to assess the effect of xrcc6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to may 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case-control studies. summary odds ratios and corresponding ...	2015	25569644
a robust method for increasing fc glycan high mannose level of recombinant antibodies.	high mannose (hm) glycoforms on antibody fc glycan are recognized as critical quality attributes for therapeutic antibody products. methods to control hm have been largely empirical, and it is challenging to target a desired hm level during antibody process development. a novel and robust method to increase antibody hm glycoforms is demonstrated in this study using multiple antibodies and cell lines without adversely impacting cell culture performance, including viable cell density, viability, a ...	2015	25565276
thromboxane a2 receptor polymorphism in association with cerebral infarction and its regulation on platelet function.	binding of thromboxane a2 (txa2) to its receptor txa2r modulates thrombosis/hemostasis and plays a vital role in the pathogenesis of cerebral infarction (ci). in this study, we investigated the relationship between txa2r polymorphisms and ci in chinese han population and the effect on platelet function by these polymorphisms. polymerase chain reaction and ligase detection reaction (pcr-ldr) was performed in 230 ci patients and 143 healthy volunteers to examine four single nucleotide polymorphism ...	2015	25557379
evaluation of gambierol and its analogs for their inhibition of human kv1.2 and cytotoxicity.	gambierol and its heptacyclic and tetracyclic analogs were tested for inhibitory activity against the human voltage-gated potassium channel kv1.2 (hkv1.2), which was stably expressed in chinese hamster ovary (cho) cells. gambierol, the heptacyclic analog, and the tetracyclic analog inhibited the potassium current evoked by a step pulse from -80mv to 40mv. the ic50 values for the three compounds were 0.75±0.15nm, 7.6±1.2nm, and 28±4.0nm (the mean±sem, n=3), respectively. the cytotoxic activity wa ...	2015	25556093
plasmid transfection in mammalian cells spatiotemporally tracked by a gold nanoparticle.	recent advances in cell transfection have suggested that delivery of a gene on a gold nanoparticle (aunp) can enhance transfection efficiency. the mechanism of transfection is poorly understood, particularly when the gene is appended to a aunp, as expression of the desired exogenous protein is dependent not only on the efficiency of the gene being taken into the cell but also on efficient endosomal escape and cellular processing of the nucleic acid. design of a multicolor surface energy transfer ...	2015	25494916
direct site-specific glycoform identification and quantitative comparison of glycoprotein therapeutics: imiglucerase and velaglucerase alfa.	gaucher disease, the most common lysosomal metabolic disorder, can be treated with enzyme replacement therapy (ert). recombinant human glucocerebrosidase imiglucerase (cerezyme(®)), produced in chinese hamster ovary cells, has been used for ert of gaucher disease for 20 years. another recombinant glucocerebrosidase velaglucerase alfa (vpriv), expressed in a human fibroblast cell line, was approved by the us food and drug administration in 2010. the amino acid sequence difference at residue 495 o ...	2015	25501675
n-glycoprofiling analysis in a simple glycoprotein model: a comparison between recombinant and pituitary glycosylated human prolactin.	human prolactin (hprl) is a polypeptide hormone occurring in the non-glycosylated (ng-hprl) and glycosylated (g-hprl) forms, with mm of approximately 23 and 25kda, respectively. it has a single, partially occupied n-glycosylation site located at asn-31, which makes it a particularly simple and interesting model for glycosylation studies. the bioactivity of g-hprl is lower than that of ng-hprl (by ca. 4-fold) and its physiological function is not clear. however, carbohydrate moieties generally pl ...	2015	25499076
comparison of methods for the analysis of therapeutic immunoglobulin g fc-glycosylation profiles--part 1: separation-based methods.	immunoglobulin g (igg) crystallizable fragment (fc) glycosylation is crucial for antibody effector functions, such as antibody-dependent cell-mediated cytotoxicity, and for their pharmacokinetic and pharmacodynamics behavior. to monitor the fc-glycosylation in bioprocess development, as well as product characterization and release analytics, reliable techniques for glycosylation analysis are needed. a wide range of analytical methods has found its way into these applications. in this study, a co ...	2015	25524468
modulation of calcium signaling of angiotensin at1, endothelin eta, and etb receptors by silibinin, quercetin, crocin, diallyl sulfides, and ginsenoside rb1.	angiotensin ii and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. both peptides exert their pleiotropic effects via binding to their respective g-protein-coupled receptors, i.e., angiotensin at1 and endothelin type a and type b receptors. in the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-menti ...	2015	25519917
evaluation of the cytotoxic and mutagenic potential of three ginkgolic acids.	ginkgolic acids (gas) are alkylphenols which can be found in the fruits and leaves of ginkgo biloba l. (ginkgoaceae) used in herbal teas, drugs and food supplements. standardized leaf extracts of g. biloba are widely used in the therapy of cognitive decline including alzheimer's diseases. however, gas are known to have cytotoxic and allergenic potential and are suspected to possess genotoxic properties. therefore, we examined in this study the cytotoxicity and mutagenicity of three major gas wit ...	2015	25448085
low dosage of rimonabant leads to anxiolytic-like behavior via inhibiting expression levels and g-protein activity of kappa opioid receptors in a cannabinoid receptor independent manner.	there is an increasing number of studies demonstrating the direct effect of the cannabinoid receptor 1 (cb1) antagonist/inverse agonist rimonabant on the opioid system. the kappa opioid receptors (kors) are well known to mediate depression- and anxiety-like behavior. clinical studies on chronic rimonabant administration have revealed that rimonabant leads to a very similar pathophysiology, suggesting a potential impact of rimonabant on kors.	2015	25446673
interaction between hydrogen sulfide-induced sulfhydration and tyrosine nitration in the katp channel complex.	hydrogen sulfide (h₂s) is an endogenous gaseous mediator affecting many physiological and pathophysiological conditions. enhanced expression of h2s and reactive nitrogen/oxygen species (rns/ros) during inflammation alters cellular excitability via modulation of ion channel function. sulfhydration of cysteine residues and tyrosine nitration are the posttranslational modifications induced by h₂s and rns, respectively. the objective of this study was to define the interaction between tyrosine nitra ...	2015	25552582
carboxylated short single-walled carbon nanotubes but not plain and multi-walled short carbon nanotubes show in vitro genotoxicity.	long carbon nanotubes (cnts) resemble asbestos fibers due to their high length to diameter ratio and they thus have genotoxic effects. another parameter that might explain their genotoxic effects is contamination with heavy metal ions. on the other hand, short (1-2 µm) cnts do not resemble asbestos fibers, and, once purified from contaminations, they might be suitable for medical applications. to identify the role of fiber thickness and surface properties on genotoxicity, well-characterized shor ...	2015	25505129
high-antibody-producing chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis.	chinese hamster ovary (cho) cells are the preferred production host for therapeutic monoclonal antibodies (mab) due to their ability to perform post-translational modifications and their successful approval history. the completion of the genome sequence for cho cells has reignited interest in using quantitative proteomics to identify markers of good production lines. here we applied two different proteomic techniques, itraq and swath, for the identification of expression differences between a hi ...	2015	25495469
mid-infrared spectroscopy-based analysis of mammalian cell culture parameters.	within the framework of process analytical technology, infrared spectroscopy (ir) has been used for characterization of biopharmaceutical production processes. although noninvasive attenuated total reflection (atr) spectroscopy can be regarded as gold standard within ir-based process analytics, simpler and more cost-effective mid-infrared (mir) instruments might improve acceptability of this technique for high-level monitoring of small scale experiments as well as for academia where financial re ...	2015	25504543
expression of difficult-to-remove host cell protein impurities during extended chinese hamster ovary cell culture and their impact on continuous bioprocessing.	during biopharmaceutical manufacturing, chinese hamster ovary (cho) cells produce hundreds of extracellular host cell protein (hcp) impurities, which must be removed from the therapeutic product by downstream purification operations to ensure patient safety. a subset of 118 of these hcps have been reported as exceptionally difficult to remove during downstream purification because they co-purify due to retention characteristics on chromatographic media and/or product-association through strongly ...	2015	25502542
conserved microrna function as a basis for chinese hamster ovary cell engineering.	the use of micrornas (mirnas) for improving the efficiency of recombinant protein production by cho cells is gaining considerable interest for their ability to regulate entire molecular networks. differential mirna expression profiling and large-scale transient screening have been the prerequisite for the selection of mirna candidates for stable manipulation, reported in cho cells expressing a range of recombinant products. we selected a potent and well characterised tumour suppressor mirna, mir ...	2015	25527440
targeting ß2 adrenergic receptors regulate human t cell function directly and indirectly.	it is well-established that central nervous system activation affects peripheral blood mononuclear cell (pbmcs) function through the release of the catecholamines (epi) and norepinephrine (ne), which act on ß2-adrenergic receptors (ß2ar). however, most studies have used non-specific stimulation of cells rather than antigen-specific responses. likewise, few studies have parsed out the direct effects of ß2ar stimulation on t cells versus indirect effects via adrenergic stimulation of antigen prese ...	2015	25526818