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https://www.readbyqxmd.com/read/28449380/the-pas-domains-of-the-major-sporulation-kinase-in-bacillus-subtilis-play-a-role-in-tetramer-formation-that-is-essential-for-the%C3%A2-autokinase-activity
#1
Brittany Kiehler, Lindsey Haggett, Masaya Fujita
Sporulation in Bacillus subtilis is induced upon starvation. In a widely accepted model, an N-terminal "sensor" domain of the major sporulation kinase KinA recognizes a hypothetical starvation signal(s) and autophosphorylates a histidine residue to activate the master regulator Spo0A via a multicomponent phosphorelay. However, to date no confirmed signal has been found. Here, we demonstrated that PAS-A, the most N-terminal of the three PAS domains (PAS-ABC), is dispensable for the activity, contrary to a previous report...
April 27, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28446174/a-scalable-metabolite-supplementation-strategy-against-antibiotic-resistant-pathogen-chromobacterium-violaceum-induced-by-nad-nadh-imbalance
#2
Deepanwita Banerjee, Dharmeshkumar Parmar, Nivedita Bhattacharya, Avinash D Ghanate, Venkateswarlu Panchagnula, Anu Raghunathan
BACKGROUND: The leading edge of the global problem of antibiotic resistance necessitates novel therapeutic strategies. This study develops a novel systems biology driven approach for killing antibiotic resistant pathogens using benign metabolites. RESULTS: Controlled laboratory evolutions established chloramphenicol and streptomycin resistant pathogens of Chromobacterium. These resistant pathogens showed higher growth rates and required higher lethal doses of antibiotic...
April 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28445477/mitochondrial-respiration-in-highly-aerobic-canines-in-the-non-raced-state-and-after-a-1600-km-sled-dog-race
#3
Benjamin Miller, Karyn Hamilton, Robert Boushel, Katherine Williamson, Verena Laner, Erich Gnaiger, Michael Davis
At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at 16 km/h to complete 1600 km. We previously demonstrated high rates of mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed rapid remodeling of mitochondrial proteins in response to energetic stress. The purpose of this study was to examine mitochondrial respiration in permeabilized skeletal muscle fibers of Alaskan Huskies in the offseason (Non-raced) and following the 1600 km Iditarod Sled Dog Race (Raced)...
2017: PloS One
https://www.readbyqxmd.com/read/28444820/casticin-impairs-cell-migration-and-invasion-of-mouse-melanoma-b16f10-cells-via-pi3k-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#4
Yung-Luen Shih, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Yung-Lin Chu, Hung-Sheng Shang, Jing-Gung Chung
Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28444480/model-based-biotechnological-potential-analysis-of-kluyveromyces-marxianus-central-metabolism
#5
A Pentjuss, E Stalidzans, J Liepins, A Kokina, J Martynova, P Zikmanis, I Mozga, R Scherbaka, H Hartman, M G Poolman, D A Fell, A Vigants
The non-conventional yeast Kluyveromyces marxianus is an emerging industrial producer for many biotechnological processes. Here, we show the application of a biomass-linked stoichiometric model of central metabolism that is experimentally validated, and mass and charge balanced for assessing the carbon conversion efficiency of wild type and modified K. marxianus. Pairs of substrates (lactose, glucose, inulin, xylose) and products (ethanol, acetate, lactate, glycerol, ethyl acetate, succinate, glutamate, phenylethanol and phenylalanine) are examined by various modelling and optimisation methods...
April 25, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28443244/the-mitochondrial-voltage-dependent-anion-channel-1-ca-2-transport-apoptosis-and-their-regulation
#6
REVIEW
Varda Shoshan-Barmatz, Soumasree De, Alon Meir
In the outer mitochondrial membrane, the voltage-dependent anion channel 1 (VDAC1) functions in cellular Ca(2+) homeostasis by mediating the transport of Ca(2+) in and out of mitochondria. VDAC1 is highly Ca(2+)-permeable and modulates Ca(2+) access to the mitochondrial intermembrane space. Intramitochondrial Ca(2+) controls energy metabolism by enhancing the rate of NADH production via modulating critical enzymes in the tricarboxylic acid cycle and fatty acid oxidation. Mitochondrial [Ca(2+)] is regarded as an important determinant of cell sensitivity to apoptotic stimuli and was proposed to act as a "priming signal," sensitizing the organelle and promoting the release of pro-apoptotic proteins...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28440822/a-carbonyl-reductase-from-candida-parapsilosis-atcc-7330-substrate-selectivity-and-enantiospecificity
#7
Sneha Sudhakara, Anju Chadha
Candida parapsilosis ATCC 7330, a rich source of highly stereospecific oxidoreductases, catalyzes oxidation-reduction of a plethora of compounds yielding industrially important intermediates. An (S)-specific carbonyl reductase (SRED) purified and characterized from this yeast is reported here. (R)-Specific carbonyl reductase (CpCR) was reported by us earlier. SRED asymmetrically reduces ketones with excellent enantiospecificity (ee > 99%) and α-ketoesters with higher catalytic activity but moderate enantiospecificity (ee 70%) in the presence of NADPH...
April 25, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28436820/srna-mediated-activation-of-gene-expression-by-inhibition-of-5-3-exonucleolytic-mrna-degradation
#8
Sylvain Durand, Frédérique Braun, Anne-Catherine Helfer, Pascale Romby, Ciarán Condon
Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can regulate the activity of these enzymes is an open question. We show that Bacillus subtilis RoxS, a major trans-acting sRNA shared with Staphylococus aureus, prevents degradation of the yflS mRNA, encoding a malate transporter...
April 24, 2017: ELife
https://www.readbyqxmd.com/read/28436453/functional-thermodynamics-structural-and-biological-studies-of-in-silico-identified-inhibitors-of-mycobacterium-tuberculosis-enoyl-acp-coa-reductase-enzyme
#9
Leonardo K B Martinelli, Mariane Rotta, Anne D Villela, Valnês S Rodrigues-Junior, Bruno L Abbadi, Rogério V Trindade, Guilherme O Petersen, Giuliano M Danesi, Laura R Nery, Ivani Pauli, Maria M Campos, Carla D Bonan, Osmar Norberto de Souza, Luiz A Basso, Diogenes S Santos
Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435050/the-human-krebs-cycle-2-oxoglutarate-dehydrogenase-complex-creates-an-additional-source-of-superoxide-hydrogen-peroxide-from-2-oxoadipate-as-alternative-substrate
#10
Natalia S Nemeria, Gary Gerfen, Elena Guevara, Pradeep Reddy Nareddy, Michal Szostak, Frank Jordan
Recently, we reported that the human 2-oxoglutarate dehydrogenase (hE1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHc) could produce the reactive oxygen species superoxide and hydrogen peroxide (detected by chemical means) from its substrate 2-oxoglutarate (OG), most likely concurrently with one-electron oxidation by dioxygen of the thiamin diphosphate (ThDP)-derived enamine intermediate to a C2α-centered radical (detected by Electron Paramagnetic Resonance) [Nemeria et al., 2014; Ambrus et al...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433189/synergic-regulation-of-redox-potential-and-oxygen-uptake-to-enhance-production-of-coenzyme-q10-in-rhodobacter-sphaeroides
#11
Yongqiang Zhu, Lidan Ye, Zhaofeng Chen, Weijiang Hu, Yanghui Shi, Jianbo Chen, Chenfei Wang, Yong Li, Weifeng Li, Hongwei Yu
The physiological role of Coenzyme Q10 (CoQ10) as an electron carrier suggests its association with redox potential. Overexpression of glyceraldehyde-3-phosphate dehydrogenase type I (gapA-1) in Rhodobacter sphaeroides elevated the NADH/NAD(+) ratio and meanwhile enhanced the CoQ10 content by 58%, but at the sacrifice of biomass. On the other hand, Vitreoscilla hemoglobin was heterologously expressed to enhance the oxygen uptake ability of the cells, leading to 127% improvement of biomass. Subsequent coexpression of gapA-1 and vgb resulted in a CoQ10 titer of 83...
June 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28431199/staphylococcus-aureus-nitric-oxide-synthase-sanos-modulates-aerobic-respiratory-metabolism-and-cell-physiology
#12
Austin B Mogen, Ronan K Carroll, Kimberly L James, Genevy Lima, Dona Silva, Jeffrey A Culver, Christopher Petucci, Lindsey N Shaw, Kelly C Rice
Nitric oxide (NO) is generated from arginine and oxygen via NO synthase (NOS). Staphylococcus aureus NOS (saNOS) has previously been shown to affect virulence and resistance to exogenous oxidative stress, yet the exact mechanism is unknown. Herein, we report a previously-undescribed role of saNOS in S. aureus aerobic physiology. Specifically, aerobic S. aureus nos mutant cultures presented with elevated endogenous reactive oxygen species (ROS) and superoxide levels, as well as increased membrane potential, increased respiratory dehydrogenase activity, and slightly elevated oxygen consumption...
April 21, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28429857/ndufa4l2-protects-against-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-and-mitochondrial-dysfunction-by-inhibiting-complex-i
#13
Jianhua Li, Caiyan Bai, Junxia Guo, Wanqian Liang, Jingning Long
Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429368/-aralar-agc1-deficiency-a-neurodevelopmental-disorder-with-severe-impairment-of-neuronal-mitochondrial-respiration-does-not-produce-a-primary-increase-in-brain-lactate
#14
Inés Juaristi, María L García-Martin, Tiago B Rodrigues, Jorgina Satrústegui, Irene Llorente-Folch, Beatriz Pardo
ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at PND 17...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428705/methemoglobinemia-living-with-dormant-devil
#15
Dhiraj J Trivedi, Bandi Joshiraj, Vijay Bidkar, Raghavendra Rao
Methemoglobin is an oxidized form of hemoglobin. NADH methemoglobin reductase deficiency or inactivity is the cause of methemoglobin. Excessive production, resulting in accumulation, causes methemoglobinemia. It can be congenital or acquired. We present a case of dormant congenital methemoglobinemia detected accidentally on preoperative assessment, due to low oxygen saturation even at F1O2-1.0 associated with central cyanosis. The patient had 27.7 % methemoglobin, living his life without any complications...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28426977/blue-violet-laser-inactivates-methicillin-resistant-staphylococcus-aureus-by-altering-its-transmembrane-potential
#16
Gabriel Biener, Daniela S Masson-Meyers, Violet V Bumah, Grant Hussey, Michael R Stoneman, Chukuka S Enwemeka, Valerica Raicu
The resistance of methicillin-resistant Staphylococcus aureus to antibiotics presents serious clinical problems that prompted the need for finding alternative or combination therapies. One such therapy is irradiation with blue light. To determine the alterations in metabolic processes implicated in the observed antimicrobial effects of blue light, we investigated the changes in membrane potential and the presence of free-radical-producing photo-acceptor molecules. Bacterial cultures irradiated with one or two doses of 405nm laser light (each consisting of 121J/cm(2)) were imaged with spectrally resolved laser-scanning microscopes to detect endogenous fluorescent species as well as the voltage sensitive dye 3,3'-Diethyloxacarbocyanine iodide...
April 6, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28425301/development-of-a-novel-rationally-designed-antibiotic-to-inhibit-a-nontraditional-bacterial-target
#17
Pavel Dibrov, Elena Dibrov, Thane G Maddaford, Melissa Kenneth, Jordan Nelson, Craig Resch, Grant N Pierce
The search for new nontraditional targets is a high priority in antibiotic design today. Bacterial membrane energetics based on sodium ion circulation offers potential alternative targets. The present work identifies the Na(+)-translocating NADH:ubiquinone oxidoreductase (Na(+)-NQR), a key respiratory enzyme in many microbial pathogens, as indispensible for the Chlamydia trachomatis infectious process. Infection by Chlamydia trachomatis significantly increased first H(+) and then Na(+) levels within the host mammalian cell...
May 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28424540/mc-ppea-as-a-new-and-more-potent-inhibitor-of-clp-induced-sepsis-and-pulmonary-inflammation-than-fk866
#18
Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P Heruth, Li Q Zhang, Dev Maulik, Shui Qing Ye
Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28424096/metabolic-and-proteomic-analyses-of-product-selectivity-and-redox-regulation-in-clostridium-pasteurianum-grown-on-glycerol-under-varied-iron-availability
#19
Christin Groeger, Wei Wang, Wael Sabra, Tyll Utesch, An-Ping Zeng
BACKGROUND: Clostridium pasteurianum as an emerging new microbial cell factory can produce both n-butanol (BuOH) and 1,3-propanediol (1,3-PDO), and the pattern of product formation changes significantly with the composition of the culture medium. Among others iron content in the medium was shown to strongly affect the products selectivity. However, the mechanism behind this metabolic regulation is still unclear. For a better understanding of such metabolic regulation and for process optimization, we carried out fermentation experiments under either iron excess or iron limitation conditions, and performed metabolic, stoichiometric and proteomic analyses...
April 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28420001/nicotinamide-n-methyltransferase-suppression-participates-in-nickel-induced-histone-h3-lysine9-dimethylation-in-beas-2b-cells
#20
Qian Li, Min-Di He, Lin Mao, Xue Wang, Yu-Lin Jiang, Min Li, Yong-Hui Lu, Zheng-Ping Yu, Zhou Zhou
BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 μM NiCl2 for different time periods...
April 13, 2017: Cellular Physiology and Biochemistry
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