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751.
Amar Bahadur Singh Chin Fung Kelvin Kan Bin Dong Jingwen Liu 《The Journal of biological chemistry》2016,291(10):5373-5384
752.
Alessandra das Graças Fedoce Frederico Ferreira Robert G. Bota Vicent Bonet-Costa Kelvin J. A. Davies 《Free radical research》2018,52(7):737-750
Anxiety disorders are the most common mental illness in the USA affecting 18% of the population. The cause(s) of anxiety disorders is/are not completely clear, and research in the neurobiology of anxiety at the molecular level is still rather limited. Although mounting clinical and preclinical evidence now indicates that oxidative stress may be a major component of anxiety pathology, whether oxidative stress is the cause or consequence remains elusive. Studies conducted over the past few years suggest that anxiety disorders may be characterised by lowered antioxidant defences and increased oxidative damage to proteins, lipids, and nucleic acids. In particular, oxidative modifications to proteins have actually been proposed as a potential factor in the onset and progression of several psychiatric disorders, including anxiety and depressive disorders. Oxidised proteins are normally degraded by the proteasome proteolytic complex in the cell cytoplasm, nucleus, and endoplasmic reticulum. The Lon protease performs a similar protective function inside mitochondria. Impairment of the proteasome and/or the Lon protease results in the accumulation of toxic oxidised proteins in the brain, which can cause severe neuronal trauma. Recent evidence points to possible proteolytic dysfunction and accumulation of damaged, oxidised proteins as factors that may determine the appearance and severity of psychotic symptoms in mood disorders. Thus, critical interactions between oxidative stress, proteasome, and the Lon protease may provide keys to the molecular mechanisms involved in emotional regulation, and may also be of great help in designing and screening novel anxiolytics and antidepressants. 相似文献
753.
Case-cohort and case-control analysis with Cox's model 总被引:1,自引:0,他引:1
754.
Abstract When a thermophilic bacillus was incubated with progesterone for approx. 18 h at 65°C, four progesterone-based metabolites were produced in moderate quantities. Two products were found to be hydroxy derivatives, i.e. 6α-hydroxyprogesterone and 6β-hydroxyprogesterone and two were C-20 reduced epimers of progesterone, i.e. 20α- and 20β-dihydroprogesterone. 6α-Hydroxyprogesterone is a rare microbial transformation product.
Inhibition of hydroxylation by azole-based fungicides and the presence of a carbon-monoxide-reduced difference-spectrum absorbance maximum at 448 nm in the soluble cell fraction suggest that the hydroxylase(s) might be cytochromes(s) P450. The dihydroprogesterones were probably produced by oxidoreductases. 相似文献
Inhibition of hydroxylation by azole-based fungicides and the presence of a carbon-monoxide-reduced difference-spectrum absorbance maximum at 448 nm in the soluble cell fraction suggest that the hydroxylase(s) might be cytochromes(s) P450. The dihydroprogesterones were probably produced by oxidoreductases. 相似文献
755.
Zhuoshi Du Seyed Pouria Motevalian Brenda Carillo-Conde Kelvin Reilly Andrew L. Zydney 《Biotechnology progress》2021,37(5):e3180
Recent studies have reported very low capacity during sterile filtration of glycoconjugate vaccines due to rapid fouling of the sterile filter. The objective of this study was to explore the potential for significantly increasing the capacity of the sterile filter through the use of an appropriate prefilter. Data were obtained using prefilters with different pore size and chemistry, with the sterile filtration performed at constant filtrate flux using 0.22 μm nominal pore size Durapore® polyvinylidene difluoride membranes. Prefiltration through 5 μm pore size Durapore® or Nylon prefilters nearly eliminated the fouling of the sterile filter, leading to more than a 100-fold reduction in the rate of pressure increase for the sterile filter. This dramatic improvement in sterile filter performance was due to the removal of large components (greater than 1 μm in size) as confirmed by dynamic light scattering. These results demonstrate the potential of using large pore size prefilters to significantly enhance the performance of the sterile filtration process for the production of important glycoconjugate vaccines. 相似文献
756.
Ameena?J. Haider Megan?H. Cox Natalie Jones Alice?J. Goode Katherine S. Bridge Kelvin Wong Deborah Briggs Ian?D. Kerr 《Bioscience reports》2015,35(4)
ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be ‘rescued’ by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2. 相似文献
757.
758.
Lauren T. Cordova Hussain Dahodwala Kathryn S. Elliott Jongyoun Baik Daniel C. Odenewelder Douglas Nmagu Bradley A. Skelton Lisa Uy Stephanie R. Klaubert Benjamin F. Synoground Dylan G. Chitwood Venkata Gayatri Dhara Harnish Mukesh Naik Caitlin S. Morris Seongkyu Yoon Michael Betenbaugh Jon Coffman Frank Swartzwelder Michael P. Gillmeister Sarah W. Harcum Kelvin H. Lee 《Biotechnology and bioengineering》2023,120(3):715-725
Due to the favorable attributes of Chinese hamster ovary (CHO) cells for therapeutic proteins and antibodies biomanufacturing, companies generate proprietary cells with desirable phenotypes. One key attribute is the ability to stably express multi-gram per liter titers in chemically defined media. Cell, media, and feed diversity has limited community efforts to translate knowledge. Moreover, academic, and nonprofit researchers generally cannot study “industrially relevant” CHO cells due to limited public availability, and the time and knowledge required to generate such cells. To address these issues, a university-industrial consortium (Advanced Mammalian Biomanufacturing Innovation Center, AMBIC) has acquired two CHO “reference cell lines” from different lineages that express monoclonal antibodies. These reference cell lines have relevant production titers, key performance outcomes confirmed by multiple laboratories, and a detailed technology transfer protocol. In commercial media, titers over 2 g/L are reached. Fed-batch cultivation data from shake flask and scaled-down bioreactors is presented. Using productivity as the primary attribute, two academic sites aligned with tight reproducibility at each site. Further, a chemically defined media formulation was developed and evaluated in parallel to the commercial media. The goal of this work is to provide a universal, industrially relevant CHO culture platform to accelerate biomanufacturing innovation. 相似文献
759.
760.
Kelvin S. Ng James A. Smith Matthew P. McAteer Benjamin E. Mead Jamie Ware Felix O. Jackson Alison Carter Lino Ferreira Kim Bure Jon A. Rowley Brock Reeve David A. Brindley Jeffrey M. Karp 《Biotechnology and bioengineering》2019,116(2):307-319
Newly recognized as natural nanocarriers that deliver biological information between cells, extracellular vesicles (EVs), including exosomes and microvesicles, provide unprecedented therapeutic opportunities. Large-scale and cost-effective manufacturing is imperative for EV products to meet commercial and clinical demands; successful translation requires careful decisions that minimize financial and technological risks. Here, we develop a decision support tool (DST) that computes the most cost-effective technologies for manufacturing EVs at different scales, by examining the costs of goods associated with using published protocols. The DST identifies costs of labor and consumables during EV harvest as key cost drivers, substantiating a need for larger-scale, higher-throughput, and automated technologies for harvesting EVs. Importantly, we highlight a lack of appropriate technologies for meeting clinical demands, and propose a potentially cost-effective solution. This DST can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes when commercializing EV products. 相似文献