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effective and efficient characterization of chinese hamster ovary production cell lines using automated intracellular staining and statistical modeling.mammalian cell line development is critical to bioproduct manufacturing. success requires selecting a line with desirable performance characteristics, including consistent expression throughout the proposed manufacturing window. given the genetic and phenotypic flux inherent to immortalized lines such as chinese hamster ovary cells, clonally-derived cell line characterization is vital. we describe here the development and implementation of a novel addition to our characterization approach to ens ...201829882242
the binding of captopril to angiotensin i-converting enzyme triggers activation of signaling pathways.hypertension is a global health problem, and angiotensin i (ang i)-converting enzyme (ace) inhibitors are largely used to control this pathology. recently, it has been shown that ace can also act as a transducer signal molecule when its inhibitors or substrates bind to it. this new role of ace could contribute to understanding some of the effects not explained by its catalytic activity only. in this study, we investigated signaling pathway activation in chinese hamster ovary (cho) cells stably e ...201829874111
a gold nanoparticle bio-optical transponder to dynamically monitor intracellular ph.a ph-sensitive bio-optical transponder (ph-bot) capable of simultaneously reporting the timing of intracellular dna cargo release from a gold nanoparticle (aunp) and the evolving intracellular ph (ph i) during endosomal maturation is demonstrated. the ph-bot is designed with a triple-dye-labeled duplex dna appended to a 6.6 nm aunp, utilizing ph-responsive fluorescein paired with dylight405 as a surface energy transfer (set) coupled dye pair to ratiometrically report the ph at and after cargo re ...201829874043
lactoferrin prevents susceptibility of wehi 231 cells to anti-ig-induced cell death promoting cell differentiation.immature b cells are susceptible to apoptosis due to ligation of surface immunoglobulin receptors. the wehi 231 cell line represents a useful model to study the mode of action of factors preventing apoptosis. in this work we investigated the protective effects of multi-species lactoferrins in anti-mouse ig-induced wehi 231 cell death. bovine milk-derived lactoferrin (blf), recombinant human lactoferrin expressed in chinese hamster ovary cells - rhlf(cho) or in human endothelial kidney cells - rh ...201829871734
amp-activated protein kinase mediates the effect of leptin on avian autophagy in a tissue-specific manner.autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and ...201829867578
crispr/cas9-multiplexed editing of chinese hamster ovary b4gal-t1, 2, 3, and 4 tailors n-glycan profiles of therapeutics and secreted host cell proteins.in production of recombinant proteins for biopharmaceuticals, n-glycosylation is often important for protein efficacy and patient safety. igg with agalactosylated (g0)-n-glycans can improve the activation of the lectin-binding complement system and be advantageous in the therapy of lupus and virus diseases. in this study, the authors aimed to engineer cho-s cells for the production of proteins with g0-n-glycans by targeting b4gal-t isoform genes with crispr/cas9. indel mutations in genes encodin ...201829862652
clonal variation in productivity and proteolytic clipping of an fc-fusion protein in cho cells: proteomic analysis suggests a role for defective protein folding and the upr.product degradation, such as clipping, is a common quality issue in the production of fc-fusion proteins from chinese hamster ovary (cho) cells. degradation of proteins is mainly due to the action of either intracellular or extracellular host cell proteases. this study was carried out to understand more fundamentally the intracellular events that may play a role in determining why cell lines from the same cell line development project can vary with regards to the extent of fc-fusion protein clip ...201829860056
a new cho (chinese hamster ovary)-derived cell line expressing anti-tnfα monoclonal antibody with biosimilar potential.tumor necrosis factor alpha (tnfα) is a pro-inflammatory cytokine that mediates the homeostasis of immune responses; its exacerbated production is associated with the pathogenesis of autoimmune and chronic inflammatory diseases. anti-tnfα drugs have revolutionized the treatment of inflammatory conditions such as rheumatoid arthritis and crohn's disease. currently, a worldwide race is on stage for the production of biosimilars moved by patent expiration of monoclonal antibodies (mabs), such as an ...201829855993
physiological responses of chinese hamster ovary cells to a productivity-enhancing yeast extract.hydrolysates play important roles in enhancing the productivity of recombinant proteins in mammalian cell cultures. lacking of detailed understanding of the mechanisms, hydrolysate is commonly regarded as an unstable factor which should be used with cautions. a yeast extract (ye) was approved to improve the fc-fusion protein productivity in a recombinant chinese hamster ovary (cho) cell line. to elucidate the responses of cells to hydrolysates, we further elaborate their physiological changes du ...201829853300
a crispr/cas9 based engineering strategy for overexpression of multiple genes in chinese hamster ovary cells.manipulation of multiple genes to engineer chinese hamster ovary (cho) cells for better performance in production processes of biopharmaceuticals has recently become more and more popular. yet, identification of useful genes and the unequivocally assessment of their effect alone and in combination(s) on the cellular phenotype is difficult due to high variation between subclones. here, we present development and proof-of-concept of a novel engineering strategy using multiplexable activation of ar ...201829852271
crispr/cas9-mediated gene knockout for dna methyltransferase dnmt3a in cho cells displays enhanced transgenic expression and long-term stability.cho cells are the preferred host for the production of complex pharmaceutical proteins in the biopharmaceutical industry, and genome engineering of cho cells would benefit product yield and stability. here, we demonstrated the efficacy of a dnmt3a-deficient cho cell line created by crispr/cas9 genome editing technology through gene disruptions in dnmt3a, which encode the proteins involved in dna methyltransferases. the transgenes, which were driven by the 2 commonly used cmv and ef1α promoters, ...201829851281
phase i trials of anti-enpp3 antibody-drug conjugates in advanced refractory renal cell carcinomas.purpose: to determine the safety, pharmacokinetics, and recommended phase ii dose of an antibody-drug conjugate (adc) targeting ectonucleotide phosphodiesterases-pyrophosphatase 3 (enpp3) conjugated to monomethyl auristatin f (mmaf) in subjects with advanced metastatic renal cell carcinoma (mrcc).patients and methods: two phase i studies were conducted sequentially with 2 adcs considered equivalent, hybridoma-derived ags-16m8f and chinese hamster ovary-derived ags-16c3f. ags-16m8f was administer ...201829848572
the effect of culture temperature on the aggregation of recombinant tnfr-fc is regulated by the perk-eif2a pathway in cho cells.recombinant human tumor necrosis factor receptor ⅱ-fc (tnfr-fc) is a therapeutic protein which is expressed in chinese hamster ovary (cho) cells. the desired tnfrfc is a dimeric form, however, polymeric tnfr-fc aggregation often occurs during cell culture which needs to be removed to minimize the potential risk of immunogenicity to patients. lowering the culture temperature is useful to improve the production of many recombinant proteins in cho cells.201829848262
crispr-based targeted epigenetic editing enables gene expression modulation of the silenced beta-galactoside alpha-2,6-sialyltransferase 1 in cho cells.despite great efforts to control and modify gene expression of chinese hamster ovary (cho) cells by conventional genetic engineering approaches, i.e. overexpression or knockdown/-out, subclonal variation, induced unknown regulatory effects as well as overexpression stress are still a major hurdle for efficient cell line engineering and for unequivocal characterization of gene function. the use of epigenetic modulators - key players in cho clonal heterogeneity - has only been marginally addressed ...201829802757
estimation of the radiation-induced dna double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus.dna double-strand breaks (dsbs) are thought to be the main cause of cell death after irradiation. in this study, we estimated the probability distribution of the number of dsbs per cell nucleus by considering the dna amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by x-ray irradiation. the probability estimation of dsb induction was made following these procedures: (i) making use of the chinese hamster ovary (cho ...201829800455
generation of high expressing chinese hamster ovary cell pools using the leap-in transposon system.clonally derived cell lines (cdcl) from chinese hamster ovary (cho) host cell lines, remain the most popular method to manufacture therapeutic proteins. however, cho cell pools are increasingly being used as an alternate method to produce therapeutic proteins for preclinical drug development in an effort to shorten the time required for new drug development. it is essential that these cho pools exhibit the desired attributes of cho cdcls such as high protein titers and consistent product quality ...201829797786
rapid development of stable transgene cho cell lines by crispr/cas9-mediated site-specific integration into c12orf35.chinese hamster ovary (cho) cells are the most widely used mammalian hosts for recombinant protein production. however, by conventional random integration strategy, development of a high-expressing and stable recombinant cho cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. site-specific integration of transgenes into cho hot spots is an ideal strategy to overcome these challenges since it can generate isogenic ...201829789882
igg responses to the plasmodium falciparum antigen var2csa in colombia are restricted to pregnancy and are not induced by exposure to plasmodium vivax.clinical immunity to malaria is associated with the acquisition of igg specific for members of the plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) family of clonally variant antigens on the surface of infected erythrocytes (ies). the var2csa subtype of pfemp1 mediates ie binding in the placenta. var2csa-specific igg is normally acquired only after exposure to placental parasites. however, it was recently reported that men and children from colombia often have high levels of functio ...201829784859
cell propagation of cholera toxin cta adp-ribosylating factor by exosome mediated transfer.in this study, we report how the cholera toxin (ct) a subunit (cta), the enzyme moiety responsible for signaling alteration in host cells, enters the exosomal pathway, secretes extracellularly, transmits itself to a cell population. the first evidence for long-term transmission of ct's toxic effect via extracellular vesicles was obtained in chinese hamster ovary (cho) cells. to follow the ct intracellular route towards exosome secretion, we used a novel strategy for generating metabolically-labe ...201829783743
the long non-coding rna transcriptome landscape in cho cells under batch and fed-batch conditions.the role of non-coding rnas in determining growth, productivity, and recombinant product quality attributes in chinese hamster ovary (cho) cells has received much attention in recent years, exemplified by studies into micrornas in particular. however, other classes of non-coding rnas have received less attention. one such class are the non-coding rnas known collectively as long non-coding rnas (lncrnas). the authors have undertaken the first landscape analysis of the lncrna transcriptome in cho ...201829781203
degradation of recombinant proteins by chinese hamster ovary host cell proteases is prevented by matriptase-1 knockout.an increasing number of nonantibody format proteins are entering clinical development. however, one of the major hurdles for the production of nonantibody glycoproteins is host cell-related proteolytic degradation, which can drastically impact developability and timelines of pipeline projects. chinese hamster ovary (cho) cells are the preferred production host for recombinant therapeutic proteins. using protease inhibitors, transcriptomics, and genetic knockdowns, we have identified, out of the ...201829777593
inactivation of deubiquitinase cyld enhances therapeutic antibody production in chinese hamster ovary cells.chinese hamster ovary (cho) cells are promising host engineering cells for industry manufacturing of therapeutic antibodies. however, cell death due to apoptosis remains a huge challenge to augment antibody production, and developing cho cells with enhanced anti-apoptosis and proliferation ability is fundamental for cell line development and high-yielding bioprocesses. deubiquitinase cylindromatosis (cyld) has been proved to be a tumor suppressor by negatively regulating nf-κb and wnt/β-catenin ...201829766242
antibody-assisted target identification reveals afatinib, an egfr covalent inhibitor, down-regulating ribonucleotide reductase.afatinib, used for the first-line treatment of non-small-cell lung carcinoma (nsclc) patients with distinct epidermal growth factor receptor (egfr) mutations, inactivates egfr by mimicking atp structure and forming a covalent adduct with egfr. we developed a method to unravel potential targets of afatinib in nsclc cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. ribonucleotide reductase (rnr) is one of target proteins of ...201829765556
reexploring 5-methoxyindole-2-carboxylic acid (mica) as a potential antidiabetic agent.5-methoxyindole-2-carboxylic acid (mica) is a potent hypoglycemic agent that inhibits gluconeogenesis in the liver. it is also a well-known inhibitor of mitochondrial dihydrolipoamide dehydrogenase. mica was extensively studied in the 1960s and 1970s and was once tested for its antidiabetic effect in diabetic chinese hamsters, whereby mica was shown to exhibit pronounced glucose-lowering ability while also leading to increased rate of death of the diabetic animals. since then, mica's potential a ...201829765243
child-onset thrombotic thrombocytopenic purpura caused by p.r498c and p.g259pfsx133 mutations in adamts13.patients suffering from congenital thrombotic thrombocytopenic purpura (cttp) have a deficiency in adamts13 due to mutations in their adamts13 gene.201829763513
an online compendium of cho rna-seq data allows identification of cho cell line-specific transcriptomic signatures.chinese hamster ovary (cho) cell lines can fold, assemble, and modify proteins post-translationally to produce human-like proteins; as a consequence, it is the single most common expression systems for industrial production of recombinant therapeutic proteins. a thorough knowledge of cultivation conditions of different cho cell lines has been developed over the last decade, but comprehending gene or pathway-specific distinctions between cho cell lines at transcriptome level remains a challenge. ...201829762913
tritium-labeled agonists as tools for studying adenosine a2b receptors.a selective agonist radioligand for a2b adenosine receptors (a2bars) is currently not available. such a tool would be useful for labeling the active conformation of the receptors. therefore, we prepared bay 60-6583, a potent and functionally selective a2bar (partial) agonist, in a tritium-labeled form. despite extensive efforts, however, we have not been able to establish a radioligand binding assay using [3h]bay 60-6583. this is probably due to its high non-specific binding and its moderate aff ...201829752618
biochemical characterization and immunogenicity of neureight, a recombinant full-length factor viii produced by fed-batch process in disposable bioreactors.hemophilia a is a x-linked recessive bleeding disorder consecutive to the lack of circulating pro-coagulant factor viii (fviii). the most efficient strategy to treat or prevent bleeding in patients with hemophilia a relies on replacement therapy using exogenous fviii. commercially available recombinant fviii are produced using an expensive perfusion technology in stainless steel fermenters. a fed-batch fermentation technology was recently developed to produce 'neureight', a full-length recombina ...201829751951
zinc supplementation decreases galactosylation of recombinant igg in cho cells.trace element composition of culture medium can be altered to modulate glycoform of recombinant glycoproteins. in this study, we show that zn2+ supplementation at or above 100 μm decreases galactosylation of recombinant igg expressed in chinese hamster ovary cells. this decrease in galactosylation is not due to reduced galactosyltransferase expression. this effect persists upon supplementation of galactose and uridine to the culture, indicating that it may not be due to reduced udp-gal availabil ...201829749563
efficient mab production in cho cells with optimized signal peptide, codon, and utr.antibody drugs have been used to treat a number of diseases successfully. producing antibodies with high yield and quality is necessary for clinical applications of antibodies. for a candidate molecule, optimization of a vector to produce sufficient yield and an accurate primary structure is indispensable in the early stage of the production process development. it is especially important to maintain the fidelity of n-terminal sequence. in order to produce antibodies with a high yield and accura ...201829740673
impact of a missense variation (p.s150r:agc>agg) in the xrcc2 gene on susceptibility to colorectal cancer.the x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2) is an important protein in response to dna double-strand breaks (dsbs) in human cells. xrcc2, as a functional protein in the homologous recombination repair (hrr) process, has been identified to have several polymorphisms which might be associated with the risk of cancer. therefore, we aimed to investigate a novel missense variation (agc>agg, p.ser150arg) in the xrcc2 gene for colorectal cancer susceptibility.201829739106
[effects of different promoters and mar combinations on transgene expression of recombinant cho cells].to analyze the effects of different promoters and matrix attachment region (mar) on the expression of transgene in chinese hamster ovary (cho) cells.201829737083
cationic lipid/dna complexes manufactured by microfluidics and bulk self-assembly exhibit different transfection behavior.recent advances in biochemical and biophysical research have been achieved through the employment of microfluidic devices. microfluidic mixing of therapeutic agents with biomaterials yields systems with finely tuned physical-chemical properties for applications in drug and gene delivery. here, we investigate the role of preparation technology (microfluidic mixing vs. bulk self-assembly) on the transfection efficiency (te) and cytotoxicity of multicomponent cationic liposome/dna complexes (lipopl ...201829733845
single copy transgene integration in a transcriptionally active site for recombinant protein synthesis.for the biomanufacturing of protein biologics, establishing stable cell lines with high transgene transcription is critical for high productivity. modern genome engineering tools can direct transgene insertion to a specified genomic locus and can potentially become a valuable tool for cell line generation. in this study, the authors survey transgene integration sites and their transcriptional activity to identify characteristics of desirable regions. a lentivirus containing destabilized green fl ...201830024101
toxicity and antigenotoxic effect of hispolon derivatives: role of structure in modulating cellular redox state and thioredoxin reductase.hispolon (hs), a bioactive polyphenol, and its derivatives such as hispolon monomethyl ether (hme), hispolon pyrazole (hp), and hispolon monomethyl ether pyrazole (hmep) were evaluated for comparative toxicity and antigenotoxic effects. the stability of hs derivatives in biological matrices followed the order hs < hp ≈ hme < hmep. the cytotoxicity analysis of hs derivatives indicated that hp and hmep were less toxic than hs and hme, respectively, in both normal and tumor cell types. the mechanis ...201830023935
control of amino acid transport into chinese hamster ovary cells.amino acid transporters (aats) represent a key interface between the cell and its environment, critical for all cellular processes: energy generation, redox control, and synthesis of cell and product biomass. however, very little is known about the activity of different functional classes of aats in chinese hamster ovary (cho) cells, how they support cell growth and productivity, and the potential for engineering their activity and/or the composition of amino acids in growth media to improve cho ...201829987891
genome sequence comparison between chinese hamster ovary (cho) dg44 cells and mouse using end sequences of cho bac clones based on bac-fish results.chinese hamster ovary (cho) cells have frequently been used in biotechnology as a mammalian host cell platform for expressing genes of interest. previously, we constructed a detailed physical chromosomal map of the cho dg44 cell line by fluorescence in situ hybridization (fish) imaging using 303 bacterial artificial chromosome (bac) clones as hybridization probes (bac-fish). bac-fish results revealed that the two longest chromosomes were completely paired. however, other chromosomes featured par ...201829987698
application of microrna targeted 3'utrs to repress dhfr selection marker expression for development of recombinant antibody expressing cho cell pools.the dihydrofolate reductase (dhfr) system is used for the selection of recombinant chinese hamster ovary (cho) cell lines using the inhibitor methotrexate (mtx). during clonal selection, endogenous dhfr expression, and resistance to mtx allows the selection of cells expressing sufficient dhfr to survive. here, the authors describe a novel vector platform for the dhfr system, whereby addition of a synthetic 3'utr destabilizes dhfr expression. mirs ability to negatively regulate gene expression by ...201829981248
paxillin phosphorylation at serine 273 and its effects on rac, rho and adhesion dynamics.focal adhesions are protein complexes that anchor cells to the extracellular matrix. during migration, the growth and disassembly of these structures are spatiotemporally regulated, with new adhesions forming at the leading edge of the cell and mature adhesions disassembling at the rear. signalling proteins and structural cytoskeletal components tightly regulate adhesion dynamics. paxillin, an adaptor protein within adhesions, is one of these proteins. its phosphorylation at serine 273 (s273) is ...201829975690
construction of anti-her2 recombinants as targeting modules for a drug-delivery system against her2-positive cells.recombinant antibodies have been investigated and used in applications such as targeting modules of drug-delivery systems (dds) against cancers. this study aimed to prepare recombinant antibodies against her2, containing sortase a (srta) recognition sequence, that are applicable as targeting modules in dds after linkage with the drug-carrier containing oligoglycine-acceptor peptide by srta transpeptidation.201829970568
the contributions of individual galactosyltransferases to protein specific n-glycan processing in chinese hamster ovary cells.galactosylation as part of n-glycan processing is conducted by a set of beta-1,4-galactosyltransferases (b4galts), with b4galt1 as the dominant isoenzyme for this reaction. nevertheless, the exact contributions of this key-player as well as of the other isoenzymes involved in n-glycosylation, b4galt2, b4galt3 and b4galt4, have not been studied in-depth. to increase the understanding of the protein- and site-specific activities of individual galactosyltransferases in chinese hamster ovary cells, ...201830017654
genotoxicity and hemocompatibility of a novel calcium aluminate-based cement.the aim of this in vitro study was to evaluate the genotoxicity and hemocompatibility of a novel calcium aluminate-based cement, endobinder (eb) (binderware, são carlos, sp, brazil) and compare it with angelus white mineral trioxide aggregate (mta) (awmta) (angelus, soluções odontológicas, londrina, pr, brazil).201832161862
simulation and experimental study on the mechanism of the chlorination of azithromycin.azithromycin (azi) has been listed as an emerging contaminant by the us epa since 2009 because it is frequently detected in wastewater, surface water, and drinking water. in this paper, the chlorination of azi in drinking water was simulated and studied. the results indicated that new compounds were generated in the chlorination of azi. the byproducts were identified by liquid chromatography-quadrupole-time-of-flight mass spectrometry (lc-q-tof), and four of the byproducts were detected in real ...201830014912
generation of flp-intm-ready dg44 and lec 3.2.8.1 cho cell lines for quick and easy constitutive protein expression.the well-characterized cell line chinese hamster ovary (cho) has been used to produce numerous biopharmaceuticals and is an important tool for basic research. however, introducing foreign dna into specially modified cho cells such as dg44 and lec 3.2.8.1 can sometimes be an arduous process. here we show that the flp-intm plasmid can be modified to produce a fluorescent tracer protein tag (mcherrytm) as a fusion reporter, to allow for the rapid selection of single-cell sorted, isogenic flp-intm-r ...201830014730
differential expression of micrornas in recombinant chinese hamster ovary cells treated with sodium butyrate using digital rna counting.sodium butyrate (nabu) is an efficient supplement for increasing recombinant protein production in chinese hamster ovary (cho) cell culture. to elucidate the effects of nabu on mirna expression profile in recombinant cho (rcho) cells, differentially expressed mirnas in nabu-treated rcho cells were assessed by nanostring ncounter analysis. this result showed that eight mature mouse mirnas (let-7b, let-7d, mir-15b, mir-25, mir-27a, mir-99a, mir-125a-5p, and mir-125b-5p) were differentially express ...201830012463
improving the production of recombinant human bone morphogenetic protein-4 in chinese hamster ovary cell cultures by inhibition of undesirable endocytosis.endocytic regulation serves a critical role in modulating the extracellular level of signaling molecules, such as bone morphogenetic proteins (bmps). unfortunately, endocytosis may result in poor yields of recombinant human bmp-4 (rhbmp-4) from chinese hamster ovary (cho) cell cultures. when rhbmp-4 was incubated with cho cells, rhbmp-4 was actively internalized into cells. cell surface bound heparan sulfate proteoglycans (hspgs) served as the major receptors for rhbmp-4 internalization. removal ...201830011067
a novel mammalian cell line development platform utilizing nanofluidics and optoelectro positioning technology.generating a highly productive cell line is resource intensive and typically involves long timelines because of the need to screen large numbers of candidates in protein production studies. this has led to miniaturization and automation strategies to allow for reductions in resources and higher throughput. current approaches rely on the use of standard cell culture vessels and bulky liquid handling equipment. new nanofludic technologies offer novel solutions to surpass these limits, further mini ...201830009534
cardiovascular pharmacology of k2p17.1 (task-4, talk-2) two-pore-domain k+ channels.k2p17.1 (task-4, talk-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. reduced k2p17.1 expression was found in atria and ventricles of heart failure (hf) patients. modulation of k2p17.1 currents by antiarrhythmic compounds has not been comprehensively studied to date. the objective of this study was to investigate acute effects of clinically relevant antiarrhythmic drugs on human k2p17.1 channel ...201830008082
single cell dielectrophoresis study of apoptosis progression induced by controlled starvation.nutrient depletion in fed-batch cultures and at the end of batch cultures is among the main causes of stress on cells and a trigger of apoptosis. in this study, we investigated changes in the cytoplasm conductivity of chinese hamster ovary (cho) cells under controlled starvation. employing a single-cell dielectrophoresis (dep) cytometer, we measured the dep response of cho cells incubated in a medium without glucose and glutamine over a 48-h period. using the measured data in conjunction with nu ...201830007208
carbon dots-decorated na2w4o13 composite with wo3 for highly efficient photocatalytic antibacterial activity.photodisinfection by semiconductors has been proven to be an effective method for achieving antibacterial or antifungal activity. however, the toxicity of the nanomaterial to the environment and organisms is a major concern. herein, a highly efficient and environmentally friendly photodisinfection material of a carbon dots (cds) decorated na2w4o13 composite with wo3 photocatalyst was fabricated via a facile hydrothermal-calcination approach. the tem (transmission electron microscopy) images show ...201830007199
n-linked glycosylation modulates the immunogenicity of recombinant human factor viii in hemophilia a mice.immune responses to factor viii remain the greatest complication in the treatment of severe hemophilia a. recent epidemiological evidence has highlighted that recombinant factor viii produced in baby hamster kidney cells is more immunogenic than factor viii produced in chinese hamster ovary cells. glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. in two hemophilia a mouse models, baby hamster kidney cell-derived factor viii elicited ...201830002126
novel bivalent and d-peptide ligands of cxcr4 mobilize hematopoietic progenitor cells to the blood in c3h/hej mice.the interaction of sdf-1α (also known as cxcl12) with the cxcr4 receptor plays a critical role in the retention of hematopoietic stem cells (hscs) in bone marrow. the viral macrophage inflammatory protein-ii (vmip-ii), a human herpesvirus-8 (hhv-8)-encoded viral chemokine, can bind the cxcr4 receptor and inhibit endogenous ligand-induced calcium responses and cell migration. previously, we used the bivalent ligand approach to link synthetically two unnatural d-amino acid peptides derived from th ...201829991278
isolation of recombinant human antithrombin isoforms by cellufine sulfate affinity chromatography.human antithrombin (hat) is a major serine protease inhibitor that regulates blood coagulation in human plasma, and it has been applied for the treatment of antithrombin (at) deficiency and disseminated intravascular coagulation (dic). in the past, hat for therapeutic use has been obtained from human plasma; however, hat can now be sourced from transgenic animals and chinese hamster ovary (cho) cells by recombinant technology. the dominant form of hat in plasma is the α form, which is glycosylat ...201830077924
the expression pattern of the phosphoproteome is significantly changed during the growth phases of recombinant cho cell culture.post-translational modification of proteins by reversible phosphorylation plays a pivotal role in regulating key cellular processes including transcription, translation, cell proliferation, differentiation, apoptosis, and signal transduction. despite the importance of the phosphorylation level of regulation, little work has been carried out on the phosphoproteomic characterization of chinese hamster ovary (cho) cells in bioprocess-relevant conditions. growth control strategies are often used to ...201830076757
pharmacological properties of asp7657, a novel, potent, and selective prostaglandin ep4 receptor antagonist.we determined the pharmacologic profile of asp7657, trans-4-[({[1-(quinolin-2-ylmethyl)-5-(trifluoromethyl)-1h-indol-7 yl] carbonyl} amino) methyl] cyclohexanecarboxylic acid methanesulfonate (1:1), a newly synthesized selective e-type prostaglandin (ep)4 receptor antagonist using several in vitro and in vivo experiments. asp7657 exhibited high affinity for rat and human ep4 receptors, with ki values of 6.02 nm and 2.21 nm, respectively. in addition, asp7657 potently inhibited the pge2-induced c ...201830076448
robotic selection for the rapid development of stable cho cell lines for hiv vaccine production.the production of envelope glycoproteins (envs) for use as hiv vaccines is challenging. the yield of envs expressed in stable chinese hamster ovary (cho) cell lines is typically 10-100 fold lower than other glycoproteins of pharmaceutical interest. moreover, envs produced in cho cells are typically enriched for sialic acid containing glycans compared to virus associated envs that possess mainly high-mannose carbohydrates. this difference alters the net charge and biophysical properties of envs a ...201830071025
egcg improves recombinant protein productivity in chinese hamster ovary cell cultures via cell proliferation control.chinese hamster ovary cell lines are good manufacturing practice-certified host cells and are widely used in the field of biotechnology to produce therapeutic antibodies. recombinant protein productivity in cells is strongly associated with cell growth. to control cell proliferation, many approaches have previously been tested including: genetic engineering, chemical additives such as cell cycle inhibitors, and temperature shift of the culture. to be widely adopted in the biopharmaceutical indus ...201830069612
media photo-degradation in pharmaceutical biotechnology - impact of ambient light on media quality, cell physiology, and igg production in cho cultures.many vital components in bioprocess media are prone to photo-conversion or photo-degradation upon exposure to ambient light, with severe negative consequences for biomass yield and overall productivity. however, there is only limited awareness of light irradiation as a potential risk factor when working in transparent glass bioreactors, storage vessels or disposable bag systems. the chemical complexity of most media renders a root-cause analysis difficult. this study investigated in a novel, hol ...201830069078
perspectives on progressive strategies and recent trends in the production of recombinant human factor viii.factor viii (fviii), a glycoprotein cofactor, plays a crucial role in the intrinsic blood coagulation pathway. as one of the most essential blood clotting factors known today, fviii is the largest and most complex commercialized therapeutic protein used in the treatment of hemophilia a, an x-linked recessive disorder. two lyophilized fviii concentrates (viz., plasma fractionated and recombinant) are in use to treat hemorrhagic episodes in patients suffering with hemophilia a. recombinant fviii ( ...201830063930
dna repair deficient chinese hamster ovary cells exhibiting differential sensitivity to charged particle radiation under aerobic and hypoxic conditions.it has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. these studies show that, when irradiated with low linear energy transfer (let) gamma-rays, poly (adp-ribose), polymerase (parp), fanconi anemia (fanc), and mutant chinese hamster ovary (cho) cells respond similar ...201830061540
activatable magnetic resonance nanosensor as a potential imaging agent for detecting and discriminating thrombosis.the early detection and accurate characterization of life-threatening diseases such as cardiovascular disease and cancer are critical to the design of treatment. knowing whether or not a thrombus in a blood vessel is new (fresh) or old (constituted) is very important for physicians to decide a treatment protocol. we have designed smart mri nano-sensors that can detect, sense and report the stage or progression of cardiovascular diseases such as thrombosis. the nanosensors were functionalized wit ...201830059122
site specificity of eel luteinizing hormone n-linked oligosaccharides in signal transduction.eel luteinizing hormone (eellh) is composed of a common α-subunit and hormone specific β-subunit, both of which contain asparagine-linked carbohydrate residues, located at positions 56 and 79 on the α-subunit and position 10 on the β-subunit. the specific roles of the individual carbohydrate chains are poorly defined in eel. thus, we characterized the biologically active single chains by fusing the α-subunit to the carboxyl terminal region of the eellh β-subunit. site-directed mutagenesis of the ...201830056138
glyco-engineered cell line and computational docking studies reveals enterotoxigenic escherichia coli cfa/i fimbriae bind to lewis a glycans.we have previously reported clinical data to suggest that colonization factor i (cfa/i) fimbriae of enterotoxigenic escherichia coli (etec) can bind to lewis a (lea), a glycan epitope ubiquitous in the small intestinal mucosa of young children (<2 years of age), and individuals with a genetic mutation of fut2. to further elucidate the physiological binding properties of this interaction, we engineered chinese hamster ovary (cho-k1) cells to express lea or leb determinants on both n- and o-glycan ...201830050155
host cell protein profiling in biopharmaceutical harvests.biopharmaceuticals contain residual host cell protein (hcp) impurities, a complex mixture of endogenous proteins from production cell lines such as chinese hamster ovary (cho) cells. the composition of hcp impurities at harvest hinges on multiple factors, e.g., identity of cell line, cell density and viability at harvest, or other process parameters. two-dimensional differential gel electrophoresis (2-d dige) was used to compare hcp in 15 null cell culture harvest supernatants, which are represe ...201830048127
fluorescence "off" and "on" signalling of esculetin in the presence of copper and thiol: a possible implication in cellular thiol sensing.the interaction of the cupric ion with esculetin, a dihydroxy coumarin derivative, was studied by absorption and fluorescence spectroscopic methods in aqueous medium. esculetin formed a complex in the presence of the cupric ion which was characterised by the shift in its absorption band from 350 nm to 389 nm and the quenching of its fluorescence intensity at 466 nm. from job's plot and fluorescence quenching studies, the stoichiometry of the copper ion and esculetin in the complex was estimated ...201830043019
chlorotyrosines versus volatile byproducts from chlorine disinfection during washing of spinach and lettuce.following the food safety modernization act of 2011 in the u.s., guidelines for disinfection washes in food packaging facilities are under consideration to control pathogen risks. however, disinfectant exposures may need optimization because the high concentrations of chlorine disinfectant promote the formation of high levels of disinfection byproducts (dbps). when chlorine doses up through the 200 mg/l as cl2 range relevant to the current practice were applied to spinach and lettuce, significan ...201830040386
development of a shake tube-based scale-down model for perfusion cultures.the use of benchtop bioreactors (brs) for the development of mammalian cell perfusion cultures is expensive and time consuming, given its complexity in equipment and operation. scale-down models, going from liter to milliliter scale, are needed to support the rapid determination of suitable operating conditions in terms of viable cell density (vcd), perfusion rate, and medium composition. in this study, we compare the performance of steady-state perfusion cultures in orbitally shaken tube and br ...201830039852
culture temperature modulates half antibody and aggregate formation in a chinese hamster ovary cell line expressing a bispecific antibody.therapeutic bispecific antibodies are formed by assembly of multichain polypeptides. in general, a bispecific antibody has two different light chains and two different heavy chains that fold and correctly pair via engineered interchain interactions. because of some incorrect assembly, product-related impurities can be prevalent (e.g., half molecules, mispaired light chains, homodimers), requiring its removal during subsequent purification. in this study, we investigated the modulation of impurit ...201830036451
cell culture medium supplemented with taurine decreases basic charge variant levels of a monoclonal antibody.to explore the impact of taurine on monoclonal antibody (mab) basic charge variants in chinese hamster ovary (cho) cell culture.201830229353
ds-8500a, an orally available g protein-coupled receptor 119 agonist, upregulates glucagon-like peptide-1 and enhances glucose-dependent insulin secretion and improves glucose homeostasis in type 2 diabetic rats.g protein-coupled receptor 119 (gpr119) has been shown to be highly expressed in small intestinal l-cells and pancreatic β-cells and mediates intracellular camp concentration, glucagon-like peptide (glp-1) secretion, and glucose-stimulated insulin secretion (gsis). this study examined the pharmacological effects of 4-(5-{(1r)-1-[4-(cyclopropylcarbonyl) phenoxy]propyl}-1,2,4-oxadiazol-3-yl)-2-fluoro-n-[(2r)-1-hydroxypropan-2-yl]benzamide (ds-8500a), a novel, orally available, selective gpr119 ago ...201830217957
pharmacological characterization of the orexin/hypocretin receptor agonist nag 26.one promising series of small-molecule orexin receptor agonists has been described, but the molecular pharmacological properties, i.e. ability and potency to activate the different orexin receptor-regulated signal pathways have not been reported for any of these ligands. we have thus here assessed these properties for the most potent ligand of the series, 4'-methoxy-n,n-dimethyl-3'-[n-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl sulfamoyl]-(1,1'-biphenyl)-3-carboxamide (nag 26). chinese hamster ...201830194937
targeting of influenza viral epitopes to antigen-presenting cells by genetically engineered chimeric molecules in a humanized nod scid gamma transfer model.antiviral dna vaccines are a novel strategy in the vaccine development field, which basically consists of the administration of expression vectors coding viral antigen sequences into the host's cells. targeting of conserved viral epitopes by antibody fragments specific to activating cell surface co-receptor molecules on antigen-presenting cells could be an alternative approach for inducing protective immunity. it has been shown that fcγri on human monocytes enhances antigen presentation in vivo. ...201830191743
construction strategies for developing expression vectors for recombinant monoclonal antibody production in cho cells.recent years have seen the use of recombinant proteins in the treatment of different diseases. among them, monoclonal antibodies (mabs) are currently the fastest growing class of bio-therapeutic recombinant proteins. chinese hamster ovary (cho) cells are the most commonly used host cells for production of these recombinant mabs. expression vectors determine the expression level and quality of recombinant mabs. currently, few construction strategies for recombinant mabs expression vectors in cho ...201830191354
rational optimization of a monoclonal antibody for simultaneous improvements in its solution properties and biological activity.developability considerations should be integrated with lead engineering of antibody drug candidates in interest of their cost effective translations into medicines. to explore feasibility of this imperative, we have performed rational mutagenesis studies on a monoclonal antibody (mab1) whose development was discontinued owing to manufacturability hurdles. seven computationally designed variants of mab1 containing single point (v44k, e59s, e59t and e59y) and double (v44ke59s, v44ke59t and v44ke5 ...201830189027
evaluation of toxicological and teratogenic effects of carbosilane glucose glycodendrimers in zebrafish embryos and model rodent cell lines.glycodendrimers (glyco-ddms) represent a rapidly growing class of nanoparticles with promising properties for biomedical applications but concerns regarding the impact on human health and environment are still justified. here we report, for the first time, the comparative study of in vivo developmental toxicity of carbosilane glyco-ddms and their cytotoxicity in vitro. carbosilane glyco-ddms (generation 1-3) containing 4, 8, and 16 β-d-glucopyranosyl units at the periphery (ddm1glu, ddm2glu, and ...201830182770
celludinones, new inhibitors of sterol o-acyltransferase, produced by talaromyces cellulolyticus bf-0307.new indanones, designated celludinones a ((±)-1) and b (2), were isolated from the culture broth of the fungal strain talaromyces cellulolyticus bf-0307. the structures of celludinones were elucidated by spectroscopic data, including 1d and 2d nmr. celludinone a was found to be a mixture of racemic isomers ((±)-1), which were isolated by a chiral column. compounds (+)-1 and (-)-1 inhibited the sterol o-acyltransferase (soat) 1 and 2 isozymes in a cell-based assay using soat1- and soat2-expressin ...201830177721
potential role of mitochondrial damage and s9 mixture including metabolic enzymes in zno nanoparticles-induced oxidative stress and genotoxicity in chinese hamster lung (chl/iu) cells.the present study was designed to examine genotoxicity induced by 10-40 nm zinc oxide (zno) nanoparticles using the in vitro system. the frequency of micronuclei was significantly increased in a dose-dependent manner when cultured chinese hamster lung (chl/iu) cells were exposed to zno nanoparticles for 24, 48 and 72 h in the continuous treatment method. the maximal frequency of micronuclei was observed in exposure of chl/iu cells to zno nanoparticles at a concentration of 125 μm. the frequency ...201830173861
direct observation of cargo transfer from hdl particles to the plasma membrane.exchange of cholesterol between high-density lipoprotein (hdl) particles and cells is a key process for maintaining cellular cholesterol homeostasis. recently, we have shown that amphiphilic cargo derived from hdl can be transferred directly to lipid bilayers. here we pursued this work using a fluorescence-based method to directly follow cargo transfer from hdl particles to the cell membrane.201830173079
model-based identification of cell-cycle-dependent metabolism and putative autocrine effects in antibody producing cho cell culture.the understanding of cell-cycle-dependent population heterogeneities in mammalian cell culture and their influence on production rates is still limited. furthermore, metabolic regulations arising from self-expressed signaling factors (autocrine/autoinhibitory factors) have been postulated in the past, but no determination of such effects have been made so far for fast-growing production chinese hamster ovary (cho) cells in chemically defined media. in this study, a novel approach combining near- ...201830171773
in vitro genotoxicity studies: n-butyl acrylate l5178y mouse lymphoma (tk+/- locus assay), 2-ethylhexyl acrylate gene mutation assay in chinese hamster v79 cells, and 2-ethylhexyl acrylate micronucleus test in human lymphocytes.available point mutation tests have shown inconsistent results with various acrylates. most of those tests were performed prior to oecd guidelines and appropriate data regarding cytotoxicity are not given. data from three current oecd guideline compliant experiments conducted under glp are provided. they include (a) an in vitro mouse lymphoma (tk+/-) assay (oecd 490) [3], (b) an in vitro hprt locus gene mutation assay utilizing cultures of chinese hamster v79 cells (oecd 476) [1], and (c) an in ...201830167439
nop receptor pharmacological profile - a dynamic mass redistribution study.the nociceptin/orphanin fq (n/ofq) peptide nop receptor is coupled to pertussis toxin (ptx)-sensitive g proteins (gi/o) whose activation leads to the inhibition of both camp production and calcium channel activity, and to the stimulation of potassium currents. the label free dynamic mass redistribution (dmr) approach has been demonstrated useful for investigating the pharmacological profile of g protein-coupled receptors. herein, we employ dmr technology to systematically characterize the pharma ...201830161182
investigating dependencies of relative biological effectiveness for proton therapy in cancer cells.relative biological effectiveness (rbe) accounts for the differences in biological effect from different radiation types. the rbe for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1. in this work we investigated the rbe of protons and correlated the biological differences with the underlying physical quantities.201830159358
differential gene expression of a feed-spiked super-producing cho cell line.feed supplements are concentrated cell culture media that contain a variety of nutrients, which can be added during a bioprocess. during fed-batch cultivation, feed media are typically added to a growing cell culture to maximize cell and product concentrations. in this study, only a single shot of feed medium was added on day 0 to a basal cell culture medium and compared to non-supplemented basal medium (feed-spiked at day 0 versus control experiments) by cultivation of a recombinant mab express ...201830157452
crispr/cas9 gene editing for the creation of an mgat1-deficient cho cell line to control hiv-1 vaccine glycosylation.over the last decade, multiple broadly neutralizing monoclonal antibodies (bn-mabs) to the hiv-1 envelope protein (env) gp120 have been described. many of these recognize epitopes consisting of both amino acid and glycan residues. moreover, the glycans required for binding of these bn-mabs are early intermediates in the n-linked glycosylation pathway. this type of glycosylation substantially alters the mass and net charge of envs compared to molecules with the same amino acid sequence but posses ...201830157178
high glucose and low specific cell growth but not mild hypothermia improve specific r-protein productivity in chemostat culture of cho cells.in the biopharmaceutical sector, chinese hamster ovary (cho) cells have become the host of choice to produce recombinant proteins (r-proteins) due to their capacity for correct protein folding, assembly, and posttranslational modification. however, the production of therapeutic r-proteins in cho cells is expensive and presents insufficient production yields for certain proteins. effective culture strategies to increase productivity (qp) include a high glucose concentration in the medium and mild ...201830114204
oligomerization and catalytic parameters of human udp-glucuronosyltransferase 1a10: expression and characterization of the recombinant protein.udp-glucuronosyltransferase (ugt), as an integral membrane protein localized in the endoplasmic reticulum, has the ability to detoxify potentially hazardous xenobiotic substances. most ugts are expressed in liver, but ugt1a10 has proven to be an extrahepatic enzyme considerably expressed throughout the gastrointestinal tract. earlier studies indicated that different ugt isoforms could exist in higher-order homo-oligomers or at least dimers within the membrane, but the formation of intermolecular ...201830111624
enhanced transgene expression using cis-acting elements combined with the ef1 promoter in a mammalian expression system.transgene expression in eukaryotic cells suffers from epigenetic effects that result in low or unstable transgene expression and high clonal variability. the use of epigenetic regulators is a promising approach to alleviating such unwanted effects. we investigated the effect of the strong human ef1-α promoter combined with six cis-acting elements on transgene expression in transfected chinese hamster ovary (cho) cells. the six elements included the human cytomegalovirus immediate early core prom ...201830110655
a mixture of atropisomers enhances neutral lipid degradation in mammalian cells with autophagy induction.atropisomers with a biaryl dihydronaphthopyranone structure, dinapinones a1 (dpa1) (m position) and a2 (dpa2) (p position), were isolated from the fungus culture broth of talaromyces pinophilus fki-3864 as inhibitors of [14c]neutral lipid ([14c]triacylglycerol (tg) and [14c]cholesteryl ester (ce)) synthesis from [14c]oleic acid in chinese hamster ovary-k1 (cho-k1) cells. dpa2 inhibited [14c]tg and [14c]ce synthesis (ic50s, 0.65 and 5.6 μm, respectively), but dpa1 had no inhibitory activity on [1 ...201830108268
isolation and characterization of a chinese hamster ovary heparan sulfate cell mutant defective in both met receptor binding and hepatocyte growth factor nk1/met signaling.the up-regulation of hepatocyte growth factor/receptor, hgf/met, signal transduction is observed in most of human cancers. specific heparan sulfate structures enhance the hgf/met signaling at both cell and animal-based model systems. biochemical studies indicate that heparan sulfate interacts with hgf and a natural occurring splicing variant nk1 of hgf with similar affinity. however, it is currently unknown if cell surface heparan sulfate binds to met at physiological conditions and if specific ...201830107380
the gagome: a cell-based library of displayed glycosaminoglycans.glycosaminoglycans (gags) are essential polysaccharides in normal physiology and disease. however, understanding of the contribution of specific gag structures to specific biological functions is limited, largely because of the great structural heterogeneity among gags themselves, as well as technical limitations in the structural characterization and chemical synthesis of gags. here we describe a cell-based method to produce and display distinct gags with a broad repertoire of modifications, a ...201830104636
detecting and imaging o-glcnac sites using glycosyltransferases: a systematic approach to study o-glcnac.o-glcnacylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells. in a given protein, o-glcnacylated and unoccupied o-linked β-n-acetylglucosamine (o-glcnac) sites are referred to as closed and open sites, respectively. the balance between open and closed sites is believed to be dynamically regulated. in this report, closed sites are detected using in vitro incorporation of galnaz by b3galnt2, and open sites are detected by in vitro inc ...201830100348
chemical characterisation and toxicity assessment in vitro and in vivo of the hydroethanolic extract of terminalia argentea mart. leaves.terminalia argentea mart. (combretaceae), known mainly as "capitão", is a native tree, not endemic, that occurs in the amazon, caatinga, cerrado and atlantic forest in brazil. leaf infusion is popularly mentioned by riverine communities that inhabit the microregion of northern araguaia (mato grosso, brazil) for the treatment of gastric ulcer, bronchitis and haemorrhage. considering the wide medicinal use, lack of studies that evaluate the safety of use and the scarcity of phytochemical studies o ...201830142424
stepwise phosphorylation of leukotriene b4 receptor 1 defines cellular responses to leukotriene b4.leukotriene b4 (ltb4) receptor type 1 (blt1) is abundant in phagocytic and immune cells and plays crucial roles in various inflammatory diseases. blt1 is phosphorylated at several serine and threonine residues upon stimulation with the inflammatory lipid ltb4 using phos-tag gel electrophoresis to separate differentially phosphorylated forms of blt1, we identified two distinct types of phosphorylation, basal and ligand-induced, in the carboxyl terminus of human blt1. in the absence of ltb4, the b ...201830131369
ligand-induced coupling between oligomers of the m2 receptor and the gi1 protein in live cells.uncertainty over the mechanism of signaling via g protein-coupled receptors (gpcrs) relates in part to questions regarding their supramolecular structure. gpcrs and heterotrimeric g proteins are known to couple as monomers under various conditions. many gpcrs form oligomers under many of the same conditions, however, and the biological role of those complexes is unclear. we have used dual-color fluorescence correlation spectroscopy to identify oligomers of the m2 muscarinic receptor and of gi1 i ...201830131171
electron donating capacity reduction of dissolved organic matter by solar irradiation reduces the cytotoxicity formation potential during wastewater chlorination.after treated wastewater is discharged into surface water for unplanned indirect potable reuse, solar irradiation transforms the dissolved organic matter (dom), which would alter the formation of disinfection byproducts (dbps) and change the cytotoxicity formation potential (ctfp) during post-chlorination in drinking water treatment plants. this study investigated the effects of solar irradiation on the ctfp and total organic halogen formation potential (toxfp) of wastewater during post-chlorina ...201830121436
effects of amino acid substitutions on the biological activity of anti-cd20 monoclonal antibody produced by transgenic silkworms (bombyx mori).recombinant monoclonal antibodies (mabs) have been used in various therapeutic applications including cancer therapy. fc-mediated effector functions play a pivotal role in the tumor-killing activities of some tumor-targeting mabs, and fc-engineering technologies with glyco-engineering or amino acid substitutions at the antibody fc region have been used to enhance cytotoxic activities including antibody-dependent cellular cytotoxicity (adcc). we previously reported that the mabs produced using tr ...201830119885
transcripts of kv7.1 and mink channels and slow delayed rectifier k+ current (iks) are expressed in zebrafish (danio rerio) heart.zebrafish are increasingly used as a model for human cardiac electrophysiology, arrhythmias, and drug screening. however, k+ ion channels of the zebrafish heart, which determine the rate of repolarization and duration of cardiac action potential (ap) are still incompletely known and characterized. here, we provide the first evidence for the presence of the slow component of the delayed rectifier k+channels in the zebrafish heart and characterize electrophysiological properties of the slow compon ...201830116893
car-t cells based on novel bcma monoclonal antibody block multiple myeloma cell growth.the cell-surface protein b cell maturation antigen (bcma, cd269) has emerged as a promising target for car-t cell therapy for multiple myeloma. in order to create a novel bcma car, we generated a new bcma monoclonal antibody, clone 4c8a. this antibody exhibited strong and selective binding to human bcma. bcma car-t cells containing the 4c8a scfv were readily detected with recombinant bcma protein by flow cytometry. the cells were cytolytic for rpmi8226, h929, and mm1s multiple myeloma cells and ...201830208593
chromawizard: an open source image analysis software for multicolor fluorescence in situ hybridization analysis.multicolor image analysis finds its applications in a broad range of biological studies. specifically, multiplex fluorescence in situ hybridization (m-fish) for chromosome painting facilitates the analysis of individual chromosomes in complex metaphase spreads and is widely used to detect both numerical and structural aberrations. while this is well established for human and mouse karyotypes, for which species sophisticated software and analysis tools are available, other organisms and species a ...201830089195
ph excursions impact cho cell culture performance and antibody n-linked glycosylation.ph excursions exist due to frequent base addition and environmental heterogeneity in large-scale bioreactors. such excursions could lead to suboptimal culture performance. here we investigated the impact of ph excursions on cell culture performance and n-linked glycosylation for three mab-producing chinese hamster ovary cell lines. frequent ph excursions were introduced by bolus base addition (in total 2-6% of initial volume, fixed bolus addition distributed from day 2 to 8) into small-scale bio ...201830088083
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