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mitochondrial engineering

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https://www.readbyqxmd.com/read/28088541/secretory-pathway-optimization-of-cho-producer-cells-by-co-engineering-of-the-mitosrna-1978-target-genes-cers2-and-tbc1d20
#1
Lisa A Pieper, Michaela Strotbek, Till Wenger, Martin Gamer, Monilola A Olayioye, Angelika Hausser
Chinese Hamster Ovary (CHO) cells are the most commonly used host for the production of biopharmaceuticals. Although transcription and translation engineering strategies have been employed to generate high-producer cell clones, the secretory pathway still remains a bottleneck in cellular productivity. In this study we show that ectopic expression of a human mitochondrial genome-encoded small RNA (mitosRNA-1978) in an IgG expressing CHO cell line strongly improved specific productivity by functioning in a microRNA-like fashion...
January 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28054019/validation-data-supporting-the-characterization-of-novel-copper-complexes-as-anticancer-agents
#2
Ceyda Acilan, Buse Cevatemre, Zelal Adiguzel, Didem Karakas, Engin Ulukaya, Nádia Ribeiro, Isabel Correia, João Costa Pessoa
Three copper(II) complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)pheamine, Cu(Sal-Gly)phepoxy were synthesized and characterized for their anticancer properties and mechanism of action (Acilan et al., in press) [1]. Here, we provide supporting data on colon cancer cell lines complementing our previous findings in cervix cells. This paper also contains a data table for the fold changes and p-values of all genes analyzed in this study via a custom RT-qPCR array. All compounds induced DNA damage (based on 8-oxo-guanidine, ɣH2AX staining in cells) and apoptosis (based on elevated DNA condensation/fragmentation, Annexin V staining, caspase 3/7 activity and mitochondrial membrane depolarization) in HCT-116 colon cancer cells...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/28038913/rlj-rgd3-induces-apoptosis-via-the-mitochondrial-dependent-pathway-and-inhibits-adhesion-migration-and-invasion-of-human-heya8-cells-via-fak-pathway
#3
Qi Jiang, Qingwei Li, Jianmei Han, Meng Gou, Yuanyuan Zheng, Bowen Li, Rong Xiao, Jihong Wang
Ovarian carcinoma is a tumor derived from ovary, which brings relatively higher mortality rate among the fatal gynecological cancers. Recently, lots of studies have concentrated on the anti-tumor effects of Arg-Gly-Asp (RGD) motif containing peptides due to their integrin binding properties. In order to meet the criterion of genetic engineering drugs, a recombinant RGD toxin protein (rLj-RGD3) without a His-tag was cloned from the buccal glands of Lampetra japonica in the present study. After endotoxin removal, the His-tag removed rLj-RGD3 was shown to inhibit the proliferation of HeyA8 cells...
December 27, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28025274/mitochondrial-phylogenomics-resolves-the-global-spread-of-higher-termites-ecosystem-engineers-of-the-tropics
#4
Thomas Bourguignon, Nathan Lo, Jan Šobotník, Simon Y W Ho, Naeem Iqbal, Eric Coissac, Maria Lee, Martin M Jendryka, David Sillam-Dussès, Barbora Křížková, Yves Roisin, Theodore A Evans
The higher termites (Termitidae) are keystone species and ecosystem engineers. They have exceptional biomass and play important roles in decomposition of dead plant matter, in soil manipulation, and as the primary food for many animals, especially in the tropics. Higher termites are most diverse in rainforests, with estimated origins in the late Eocene (∼54 Ma), postdating the breakup of Pangaea and Gondwana when most continents became separated. Since termites are poor fliers, their origin and spread across the globe requires alternative explanation...
December 25, 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28011589/maternal-engineered-nanomaterial-exposure-disrupts-progeny-cardiac-function-and-bioenergetics
#5
Quincy A Hathaway, Cody E Nichols, Danielle L Shepherd, Phoebe A Stapleton, Sarah L Mclaughlin, Janelle C Stricker, Stephanie L Rellick, Mark V Pinti, Alaeddin B Abukabda, Caroll R McBride, Jinghai Yi, Seth M Stine, Timothy R Nurkiewicz, John M Hollander
Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The current study was designed to determine whether gestational nano-TiO2 exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague Dawley rats were exposed to nano-TiO2 aerosols (~10 mg/m(3), 130 - 150 nm count median aerodynamic diameter) for 7-8 non-consecutive days beginning at gestational day 5-6. Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points: fetal (gestational day 20), neonatal (4-10 days), and young adult (6-12 weeks) were evaluated...
December 23, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27994461/biofabrication-of-a-novel-biomolecule-assisted-reduced-graphene-oxide-an-excellent-biocompatible-nanomaterial
#6
Xi-Feng Zhang, Sangiliyandi Gurunathan
Graphene has been shown much interest, both in academics and industry due to its extraordinary physical, chemical, and biological proprieties. It shows great promises in biotechnological and biomedical applications as an antibacterial and anticancer agent, nanocarrier, sensor, etc. However, many studies demonstrated the toxicity of graphene in several cell lines, which is an obstacle to its use in biomedical applications. In this study, to improve the biocompatibility of graphene, we used nicotinamide (NAM) as a reducing and stabilizing agent to catalyze the reduction of graphene oxide (GO) to reduced graphene oxide (rGO)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27987887/alginate-and-gelatin-based-bioactive-photocross-linkable-hybrid-materials-for-bone-tissue-engineering
#7
Joanna Lewandowska-Łańcucka, Katarzyna Mystek, Arn Mignon, Sandra Van Vlierberghe, Anna Łatkiewicz, Maria Nowakowska
The paper presents the synthesis, the physico-chemical and the biological properties of novel hybrid materials prepared from photo-crosslinked gelatin/alginate-based hydrogels and silica particles exhibiting potential for the regeneration of bone tissue. Both alginate and gelatin were functionalized with methacrylate and methacrylamide moieties, respectively to render them photo-crosslinkable. Submicron silica particles of two sizes were dispersed within three types of polymeric sols including alginate, gelatin, and gelatin/alginate blends, which were subsequently photo-crosslinked...
February 10, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27974733/enhanced-production-of-itaconic-acid-through-development-of-transformed-fungal-strains-of-aspergillus-terreus
#8
Woo-Shik Shin, Boonyoung Park, Dohoon Lee, Min-Kyu Oh, Gie-Taek Chun, Sangyong Kim
Metabolic engineering with a high-yielding mutant, A. terreus AN37 was performed to enhance the production of itaconic acid (IA). Reportedly, the gene cluster for IA biosynthesis is composed of four genes: reg (regulator), mtt (mitochondrial transporter), cad (cis-aconitate decarboxylase), and mfs (membrane transporter). By overexpressing each gene of the IA gene cluster in A. terreus AN37 transformed by REMI method, several transformants showing high productivity of IA were successfully obtained. One of the AN37/cad transformants could produce very high amount of IA (75 g/l) in shake-flask cultivations, showing an average of 5% higher IA titer compared to the high-yielding control strain...
December 14, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27935327/activation-induced-cell-death-aicd-of-human-melanoma-antigen-specific-tcr-engineered-cd8-t-cells-involves-jnk-bim-and-p53
#9
Arvind Chhabra, Bijay Mukherji, Deepika Batra
OBJECTIVES: Adoptive cancer immunotherapy (ACT) with transgenic T cell receptor (TCR) engineered (TCReng) anti-tumor T cells has produced encouraging results, however, efficacy of these approaches need improvement. Since premature activation induced cell death (AICD) of adoptively administered T cells could be a major impediment, we examined the mechanism(s) underlying AICD in TCReng CD8+ cytolytic T lymphocytes (CTL). METHODS: AICD in human tumor antigen-specific MHC class I restricted TCR engineered CD8+ CTL was induced by exposing them to cognate peptide epitope...
December 20, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27924712/cytotoxicity-of-carbon-nanohorns-in-different-human-cells-of-the-respiratory-system
#10
Franziska Schramm, Martina Lange, Pia Hoppmann, Astrid Heutelbeck
One of the new synthetic carbon-based nanomaterials is carbon nanohorns (CNH). A potential risk for employees of production processes is an unintentional intake of these nanomaterials via inhalation. Once taken up, nanoparticles might interact with cells of different tissues as well as with intercellular substances. These interactions may have far-reaching consequences for human health. Currently, many gaps in available information on the CNH toxicological profile remain. The aim of this study was to determine the cytotoxicity of CNH particles on human epithelial cells of the respiratory system with special consideration given to different particle sizes...
2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27904677/an-engineered-fgf21-variant-ly2405319-can-prevent-non-alcoholic-steatohepatitis-by-enhancing-hepatic-mitochondrial-function
#11
Ju Hee Lee, Yea Eun Kang, Joon Young Chang, Ki Cheol Park, Hyeon-Woo Kim, Jung Tae Kim, Hyun Jin Kim, Hyon-Seung Yi, Minho Shong, Hyo Kyun Chung, Koon Soon Kim
Non-alcoholic fatty liver disease (NAFLD) is a prevalent obesity-related disease that affects large populations throughout the world due to excessive calorie intake and an increasingly sedentary lifestyle. Fibroblast growth factor 21 (FGF21) has recently emerged as a promising therapeutic candidate for the treatment of obesity and diabetes. FGF21 is a starvation-induced pleiotropic hormone with various beneficial metabolic effects, and pharmacological treatment in rodents has been shown to improve insulin sensitivity and decrease simple fatty liver disease...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27892457/amplification-of-usp13-drives-ovarian-cancer-metabolism
#12
Cecil Han, Lifeng Yang, Hyun Ho Choi, Joelle Baddour, Abhinav Achreja, Yunhua Liu, Yujing Li, Jiada Li, Guohui Wan, Cheng Huang, Guang Ji, Xinna Zhang, Deepak Nagrath, Xiongbin Lu
Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881304/mitochondrial-sirtuin-network-reveals-dynamic-sirt3-dependent-deacetylation-in-response-to-membrane-depolarization
#13
Wen Yang, Koji Nagasawa, Christian Münch, Yingjie Xu, Kyle Satterstrom, Seungmin Jeong, Sebastian D Hayes, Mark P Jedrychowski, F Sejal Vyas, Elma Zaganjor, Virginia Guarani, Alison E Ringel, Steven P Gygi, J Wade Harper, Marcia C Haigis
Mitochondrial sirtuins, SIRT3-5, are NAD(+)-dependent deacylases and ADP-ribosyltransferases that are critical for stress responses. However, a comprehensive understanding of sirtuin targets, regulation of sirtuin activity, and the relationships between sirtuins remains a key challenge in mitochondrial physiology. Here, we employ systematic interaction proteomics to elucidate the mitochondrial sirtuin protein interaction landscape. This work reveals sirtuin interactions with numerous functional modules within mitochondria, identifies candidate sirtuin substrates, and uncovers a fundamental role for sequestration of SIRT3 by ATP synthase in mitochondrial homeostasis...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27869295/-noninvasive-assessment-of-tissue-engineered-graft-viability-by-oxygen-17-magnetic-resonance-spectroscopy
#14
Samuel A Einstein, Bradley P Weegman, Jennifer P Kitzmann, Klearchos K Papas, Michael Garwood
Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy ((17) O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with (17) O2 can also enable measurements of TEG viability...
November 21, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27852805/computational-properties-of-mitochondria-in-t-cell-activation-and-fate
#15
REVIEW
Roman Uzhachenko, Anil Shanker, Geneviève Dupont
In this article, we review how mitochondrial Ca(2+) transport (mitochondrial Ca(2+) uptake and Na(+)/Ca(2+) exchange) is involved in T cell biology, including activation and differentiation through shaping cellular Ca(2+) signals. Based on recent observations, we propose that the Ca(2+) crosstalk between mitochondria, endoplasmic reticulum and cytoplasm may form a proportional-integral-derivative (PID) controller. This PID mechanism (which is well known in engineering) could be responsible for computing cellular decisions...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27847988/metabolically-engineered-saccharomyces-cerevisiae-for-enhanced-isoamyl-alcohol-production
#16
Jifeng Yuan, Xue Chen, Pranjul Mishra, Chi-Bun Ching
Higher chain alcohols have gained much attention as next generation transport fuels because of their higher energy density and low moisture absorption capacity compared to ethanol. In the present study, we attempted to engineer Saccharomyces cerevisiae for the synthesis of isoamyl alcohol via de novo leucine biosynthetic pathway coupled with Ehrlich degradation pathway. To achieve high-level production of isoamyl alcohol, two strategies are used in the current study: (1) reconstruction of a chromosome-based leucine biosynthetic pathway under the control of galactose-inducible promoters; (2) overexpression of the mitochondrial 2-isopropylmalate (α-IPM) transporter to boost the transportation of α-IPM from mitochondria to the cytosol...
January 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27832395/mitoluhmes-an-engineered-neuronal-cell-line-for-the-analysis-of-the-motility-of-mitochondria
#17
Tomasz M Stępkowski, Sylwia Męczyńska-Wielgosz, Marcin Kruszewski
Perturbations in the transport of mitochondria and their quality control in neuronal cells underlie many types of neurological pathologies, whereas systems enabling convenient analysis of mitochondria behavior in cellular models of neurodegenerative diseases are limited. In this study, we present a modified version of lund human mesencephalic cells, mitoLUHMES, expressing GFP and mitochondrially targeted DsRed2 fluorescent proteins, intended for in vitro analysis of mitochondria trafficking by real-time fluorescence microscopy...
November 10, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27786171/engineered-aaa-proteases-reveal-principles-of-proteolysis-at-the-mitochondrial-inner-membrane
#18
Hui Shi, Anthony J Rampello, Steven E Glynn
The human YME1L protease is a membrane-anchored AAA+ enzyme that controls proteostasis at the inner membrane and intermembrane space of mitochondria. Understanding how YME1L recognizes substrates and catalyses ATP-dependent degradation has been hampered by the presence of an insoluble transmembrane anchor that drives hexamerization of the catalytic domains to form the ATPase active sites. Here, we overcome this limitation by replacing the transmembrane domain with a soluble hexameric coiled coil to produce active YME1L hexamers that can be studied in vitro...
October 27, 2016: Nature Communications
https://www.readbyqxmd.com/read/27785022/cytotoxic-effects-of-zno-nanoparticles-on-mouse-testicular-cells
#19
Zhe Han, Qi Yan, Wei Ge, Zhi-Guo Liu, Sangiliyandi Gurunathan, Massimo De Felici, Wei Shen, Xi-Feng Zhang
BACKGROUND: Nanoscience and nanotechnology are developing rapidly, and the applications of nanoparticles (NPs) have been found in several fields. At present, NPs are widely used in traditional consumer and industrial products, however, the properties and safety of NPs are still unclear and there are concerns about their potential environmental and health effects. The aim of the present study was to investigate the potential toxicity of ZnO NPs on testicular cells using both in vitro and in vivo systems in a mouse experimental model...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27775718/correcting-mitochondrial-fusion-by-manipulating-mitofusin-conformations
#20
Antonietta Franco, Richard N Kitsis, Julie A Fleischer, Evripidis Gavathiotis, Opher S Kornfeld, Guohua Gong, Nikolaos Biris, Ann Benz, Nir Qvit, Sara K Donnelly, Yun Chen, Steven Mennerick, Louis Hodgson, Daria Mochly-Rosen, Gerald W Dorn
Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is not completely understood. Here we show that mitofusins adopt either a fusion-constrained or a fusion-permissive molecular conformation, directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated in mouse cells by targeting these conformational transitions...
1, 2016: Nature
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