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https://www.readbyqxmd.com/read/27924712/cytotoxicity-of-carbon-nanohorns-in-different-human-cells-of-the-respiratory-system
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
November 15, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27832395/mitoluhmes-an-engineered-neuronal-cell-line-for-the-analysis-of-the-motility-of-mitochondria
#8
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
#9
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
#10
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
#11
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 Ii
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...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27773706/synthesis-biological-characterization-and-evaluation-of-molecular-mechanisms-of-novel-copper-complexes-as-anticancer-agents
#12
Ceyda Acilan, Buse Cevatemre, Zelal Adiguzel, Didem Karakas, Engin Ulukaya, Nádia Ribeiro, Isabel Correia, João Costa Pessoa
BACKGROUND: To overcome the hurdles of cisplatin, majorly its toxicity and resistance, there has been extensive search for alternative anti-cancer metal-based compounds. Here, three Cu(II)-complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)(pheamine), Cu(Sal-Gly)(phepoxy) are characterized for their interaction with DNA, cytotoxicity and mechanism of action. METHODS: The binding ability of the complexes to Calf-Thymus DNA was evaluated by competition fluorescence studies with thiazole-orange, UV-Vis and circular dichroism spectroscopic titrations...
October 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27741250/directed-evolution-reveals-unexpected-epistatic-interactions-that-alter-metabolic-regulation-and-enable-anaerobic-xylose-use-by-saccharomyces-cerevisiae
#13
Trey K Sato, Mary Tremaine, Lucas S Parreiras, Alexander S Hebert, Kevin S Myers, Alan J Higbee, Maria Sardi, Sean J McIlwain, Irene M Ong, Rebecca J Breuer, Ragothaman Avanasi Narasimhan, Mick A McGee, Quinn Dickinson, Alex La Reau, Dan Xie, Mingyuan Tian, Jennifer L Reed, Yaoping Zhang, Joshua J Coon, Chris Todd Hittinger, Audrey P Gasch, Robert Landick
The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27732868/comparative-genomics-analysis-of-a-series-of-yarrowia-lipolytica-wsh-z06-mutants-with-varied-capacity-for-%C3%AE-ketoglutarate-production
#14
Weizhu Zeng, Fang Fang, Song Liu, Guocheng Du, Jian Chen, Jingwen Zhou
Yarrowia lipolytica is one of the most intensively investigated α-ketoglutaric acid (α-KG) producers, and metabolic engineering has proven effective for enhancing production. However, regulation of α-KG metabolism remains poorly understood. Genetic engineering of new strains is accompanied by potential safety concerns in some countries and regions. A series of mutants with varied capacity for α-KG production were obtained using random mutagenesis of Y. lipolytica WSH-Z06. Comparative genomics analysis was implemented to identify genes candidates associated with α-KG production...
October 11, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27721655/casp8p41-the-protean-mediator-of-death-in-cd4-t-cells-that-replicate-hiv
#15
Rahul Sampath, Nathan W Cummins, Andrew D Badley
HIV cure is now the focus of intense research after Timothy Ray Brown (the Berlin patient) set the precedent of being the first and only person cured. A major barrier to achieving this goal on a meaningful scale is an elimination of the latent reservoir, which is thought to comprise CD4-positive cells that harbor integrated, replication-competent HIV provirus. These cells do not express viral proteins, are indistinguishable from uninfected CD4 cells, and are thought to be responsible for HIV viral rebound-that occurs within weeks of combination anti retroviral therapy (cART) interruption...
2016: Journal of Cell Death
https://www.readbyqxmd.com/read/27720947/the-plant-derived-triterpenoid-tingenin-b-is-a-potent-anticancer-agent-due-to-its-cytotoxic-activity-on-cancer-stem-cells-of-breast-cancer-in%C3%A2-vitro
#16
Buse Cevatemre, Bruno Botta, Mattia Mori, Simone Berardozzi, Cinzia Ingallina, Engin Ulukaya
Despite the rapid advances in chemotherapy regimens, the outcome of patients with breast cancer is not satisfactory. One of the reasons of this dissatisfaction is that subsets of cells in tumors which referred as cancer stem cells (CSCs) show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. Since some are already used in the clinic, natural products have great potential for further development as anti cancer drugs. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22β-hydroxytingenone) which is a quinone-methide triterpenoid structurally related to tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell line, MCF-7s)...
October 5, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27714634/zinc-oxide-nanoparticle-induces-microglial-death-by-nadph-oxidase-independent-reactive-oxygen-species-as-well-as-energy-depletion
#17
Anuj Kumar Sharma, Vikas Singh, Ruchi Gera, Mahaveer Prasad Purohit, Debabrata Ghosh
Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27709573/insertion-of-group-ii-intron-based-ribozyme-switches-into-homing-endonuclease-genes
#18
Tuhin Kumar Guha, Georg Hausner
Fungal mitochondrial genomes act as "reservoirs" for homing endonucleases. These enzymes with their DNA site-specific cleavage activities are attractive tools for genome editing, targeted mutagenesis and gene therapy applications. Herein, we present strategies where homing endonuclease open reading frames (HEases ORFs) are interrupted with group II intron sequences. The ultimate goal is to achieve in vivo expression of HEases that can be regulated by manipulating the splicing efficiency of the HEase ORF-embedded group II introns...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27694050/biopolymeric-hydrogels-nanostructured-tio2-hybrid-materials-as-potential-injectable-scaffolds-for-bone-regeneration
#19
Karolina Zazakowny, Joanna Lewandowska-Łańcucka, Joanna Mastalska-Popławska, Kamil Kamiński, Anna Kusior, Marta Radecka, Maria Nowakowska
The present work aims at development of novel hybrid materials from genipin crosslinked collagen or collagen/chitosan hydrogels containing various types of TiO2 nanoparticles characterized with different anatase/rutile ratios. Collagen and chitosan were selected as hydrogel components since they are biopolymers being, like collagen, the major compound present in extracellular matrix or exhibit structural similarity to glycosaminoglycans, like chitosan. TiO2 nanoparticles were introduced to the hydrogel matrices to improve their mechanical properties as well as bioactivity...
September 22, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27679559/enhanced-glut4-dependent-glucose-transport-relieves-nutrient-stress-in-obese-mice-through-changes-in-lipid-and-amino-acid-metabolism
#20
Jami M Gurley, Olga Ilkayeva, Robert M Jackson, Beth A Griesel, Phillip White, Satochi Matsuzaki, Rizwan Qaisar, Holly Van Remmen, Kenneth M Humphries, Christopher B Newgard, Ann Louise Olson
Impaired GLUT4-dependent glucose uptake is a contributing factor in the development of whole-body insulin resistance in obese patients and obese animal models. Previously, we demonstrated that transgenic mice engineered to express the human GLUT4 gene under the control of the human GLUT4 promoter (i.e., transgenic [TG] mice) are resistant to obesity-induced insulin resistance. A likely mechanism underlying increased insulin sensitivity is increased glucose uptake in skeletal muscle. The purpose of this study was to investigate the broader metabolic consequences of enhanced glucose uptake into muscle...
December 2016: Diabetes
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