<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chandrawanshi, Vikas</style></author><author><style face="normal" font="default" size="100%">Kulkarni, Rohan</style></author><author><style face="normal" font="default" size="100%">Prabhu, Anuja</style></author><author><style face="normal" font="default" size="100%">Mehra, Sarika</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Enhancing titers and productivity of rCHO clones with a combination of an optimized fed-batch process and ER-stress adaptation</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Biotechnology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adaptive laboratory evolution</style></keyword><keyword><style  face="normal" font="default" size="100%">CHO cells</style></keyword><keyword><style  face="normal" font="default" size="100%">ER-stress</style></keyword><keyword><style  face="normal" font="default" size="100%">Fed-batch</style></keyword><keyword><style  face="normal" font="default" size="100%">Increased productivity and titers</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant protein production</style></keyword><keyword><style  face="normal" font="default" size="100%">UPR pathway</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">MAR</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">311</style></volume><pages><style face="normal" font="default" size="100%">49-58</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;To increase the productivity of rCHO cells, many cell engineering approaches have been demonstrated that over-express or knockout a specific gene to achieve increased titers. In this work, we present an alternate approach, based on the concept of evolutionary adaptation, to achieve cells with higher titers. rCHO cells, producing a monoclonal antibody, are adapted to ER-stress, by continuous culturing under increasing concentration of tunicamycin. A sustained higher productivity of at-least 2-fold was achieved in all the clones, in a concentration-dependent manner. Similarly, a 1.5-2 fold increase in final titers was also achieved in the batch culture. Based on metabolic analysis of the adapted cells, a fed-batch process was designed where significantly higher titersare achieved as compared to control. Metabolic flux analysis is employed in addition with gene expression analysis of key genes to understand the basis of increased performance of the adapted cells. Overall, this work illustrates how process modifications and cellular adaptation can be used in synergy to drive up product titers.&lt;/p&gt;
</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;3.503&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ghosh, Saptarshi</style></author><author><style face="normal" font="default" size="100%">Cotta, Karishma Berta</style></author><author><style face="normal" font="default" size="100%">Hande, Aniket A.</style></author><author><style face="normal" font="default" size="100%">Fernandes, Moneesha</style></author><author><style face="normal" font="default" size="100%">Mehra, Sarika</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">PNA-mediated efflux inhibition as a therapeutic strategy towards overcoming drug resistance in Mycobacterium smegmatis</style></title><secondary-title><style face="normal" font="default" size="100%">Microbial Pathogenesis</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adjuvant</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibiotic resistance</style></keyword><keyword><style  face="normal" font="default" size="100%">Antisense</style></keyword><keyword><style  face="normal" font="default" size="100%">Efflux pump</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene silencing</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacteria</style></keyword><keyword><style  face="normal" font="default" size="100%">Peptide nucleic acid (PNA)</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">FEB</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">151</style></volume><pages><style face="normal" font="default" size="100%">104737</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The emergence of antibiotic-resistant strains of Mycobacterium tuberculosis and the decelerating development of new and effective antibiotics has impaired the treatment of tuberculosis (TB). Efflux pump inhibitors (EPIs) have the potential to improve the efficacy of existing anti-TB drugs although with toxicity limitations. Peptide nucleic acids (PNAs), oligonucleotide mimics, by virtue of their high nucleic acid binding specificity have the capability to overcome this drawback. We, therefore, investigated the efflux pump inhibitory properties of a PNA designed against an efflux pump of Mycobacterium smegmatis. LfrA, an efflux pump found in M. smegmatis, is majorly involved in conferring innate drug resistance to this strain and, therefore, was selected as a target for gene silencing via PNA. qRT-PCR and EtBr assays confirmed the EPI activity of the anti-lfrA PNA. On testing the effect of the anti-lfrA PNA on the bactericidal activity of a fluoroquinolone, norfloxacin, we observed that 5 mu M of anti-lfrA PNA in combination with norfloxacin led to an enhanced killing of up to 2.5 log-fold against wild-type and a lab-generated multidrug resistant strain, exemplifying its potential in countering resistance. Improved efficacy was also observed against intra-macrophage mycobacteria, where the drug-PNA combination enhanced bacterial clearance by 1.3 log-fold. Further, no toxicity was observed with PNA concentrations up to 4 times higher than the efficacious anti-lfrA PNA concentration. Thus, PNA, as an adjuvant, presents a novel and viable approach to rejuvenate anti-TB therapeutics.&lt;/p&gt;
</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;
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