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https://www.readbyqxmd.com/read/28642444/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#1
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641509/brain-information-sharing-during-visual-short-term-memory-binding-yields-a-memory-biomarker-for-familial-alzheimer-s-disease
#2
Mario A Parra, Ezequiel Mikulan, Natalia Trujillo, Sergio Della Sala, Francisco Lopera, Facundo Manes, John Starr, Agustin Ibanez
BACKGROUND: Alzheimer's disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. OBJECTIVE: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. METHODS: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG...
June 14, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28640638/enzyme-mediated-conversion-of-fad-to-8-formyl-fad-in-formate-oxidase-results-in-modified-cofactor-with-enhanced-catalytic-properties
#3
John M Robbins, Michael G Souffrant, Donald Hamelberg, Giovanni Gadda, Andreas S Bommarius
Flavins, including flavin adenine dinucleotide (FAD), are fundamental catalytic cofactors responsible for the redox functionality of a diverse set of proteins. Alternatively, modified flavin analogues are rarely found in nature as their incorporation typically results in inactivation of flavoproteins, thus leading to the disruption of important cellular pathways. Here, we report that the fungal flavoenzyme formate oxidase (FOX) catalyzes the slow conversion of non-covalently bound FAD to 8-formyl FAD (8-fFAD), and that this conversion results in a nearly 10-fold increase in formate oxidase activity...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28634712/site-directed-mutagenesis-under-the-direction-of-in-silico-protein-docking-modeling-reveals-the-active-site-residues-of-3-ketosteroid-%C3%AE-1-dehydrogenase-from-mycobacterium-neoaurum
#4
Ning Qin, Yanbing Shen, Xu Yang, Liqiu Su, Rui Tang, Wei Li, Min Wang
3-Ketosteroid-Δ(1)-dehydrogenases (KsdD) from Mycobacterium neoaurum could transform androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione. This reaction has a significant effect on the product of pharmaceutical steroid. The crystal structure and active site residues information of KsdD from Mycobacterium is not yet available, which result in the engineering of KsdD is tedious. In this study, by the way of protein modeling and site-directed mutagenesis, we find that, Y122, Y125, S138, E140 and Y541 from the FAD-binding domain and Y365 from the catalytic domain play a key role in this transformation...
July 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28634231/hyperactivity-of-the-arabidopsis-cryptochrome-cry1-l407f-mutant-is-caused-by-a-structural-alteration-close-to-the-cry1-atp-binding-sit
#5
Christian Orth, Nils Niemann, Lars Hennig, Lars-Oliver Essen, Alfred Batschauer
Plant cryptochromes (cry) act as UV-A/blue light receptors. The prototype, Arabidopsis thaliana cry1, regulates several light responses during the life cycle, including de-etiolation, and is also involved in regulating flowering time. The cry1 photocycle is initiated by light absorption by its FAD chromophore, which is most likely fully oxidized (FADox) in the dark state and photoreduced to the neutral flavin semiquinone (FADH(o)) in its lit state. Cryptochromes lack the DNA-repair activity of the closely related DNA photolyases, but retain the ability to bind nucleotides such as ATP...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28633821/enhanced-production-of-hypocrellin-a-by-ultrasound-stimulation-in-submerged-cultures-of-shiraia-bambusicola
#6
Chun Xiao Sun, Yan Jun Ma, Jian Wen Wang
Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28W/cm(2) at 40kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12h to stimulate HA production of Shiraia bambusicola after 72h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#7
Ming-Yeh Yang, Chih-Jui Chang, Liang-Yü Chen
Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm)...
June 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28630487/multicolor-two-photon-imaging-of-endogenous-fluorophores-in-living-tissues-by-wavelength-mixing
#8
Chiara Stringari, Lamiae Abdeladim, Guy Malkinson, Pierre Mahou, Xavier Solinas, Isabelle Lamarre, Sébastien Brizion, Jean-Baptiste Galey, Willy Supatto, Renaud Legouis, Ana-Maria Pena, Emmanuel Beaurepaire
Two-photon imaging of endogenous fluorescence can provide physiological and metabolic information from intact tissues. However, simultaneous imaging of multiple intrinsic fluorophores, such as nicotinamide adenine dinucleotide(phosphate) (NAD(P)H), flavin adenine dinucleotide (FAD) and retinoids in living systems is generally hampered by sequential multi-wavelength excitation resulting in motion artifacts. Here, we report on efficient and simultaneous multicolor two-photon excitation of endogenous fluorophores with absorption spectra spanning the 750-1040 nm range, using wavelength mixing...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627257/toward-the-development-of-a-glucose-dehydrogenase-based-saliva-glucose-sensor-without-the-need-for-sample-preparation
#9
Chi Lin, Breanna Pratt, Mackenzie Honikel, Alaina Jenish, Bhavna Ramesh, Amnah Alkhan, Jeffrey T La Belle
BACKGROUND: Strict glycemic control is known to be a vital key in the management of diabetes mellitus (DM). However, traditional methods face limitations in their efficacy due to the pain and invasiveness of needle pricking which often discourages DM patients from performing the required number of tests per day. Saliva glucose (SG) sensing has long been considered a noninvasive alternative to blood glucose monitoring for diabetes management, however the sample preparation and sensor detection limit have been deemed as challenges to overcome...
June 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28625985/periplasmic-nicotine-dehydrogenase-ndhab-utilizes-pseudoazurin-as-its-physiological-electron-acceptor-in-agrobacterium-tumefaciens-s33
#10
Wenjun Yu, Rongshui Wang, Haiyan Huang, Huijun Xie, Shuning Wang
Agrobacterium tumefaciens S33 can grow with nicotine as the sole source of carbon, nitrogen, and energy via a novel hybrid of the pyridine pathway and the pyrollidine pathway. Characterization of the enzymes involved in the hybrid pathway is important for understanding its biochemical mechanism. Here we report that the molybdenum-containing nicotine dehydrogenase (NdhAB), which catalyzes the initial step of nicotine degradation, is located in the periplasm of strain S33, while the 6-hydroxynicotine oxidase and 6-hydroxypseudooxynicoine oxidase are in the cytoplasm...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28625766/amine-oxidation-by-d-arginine-dehydrogenase-in-pseudomonas-aeruginosa
#11
REVIEW
Daniel Ouedraogo, Jacob Ball, Archana Iyer, Renata A G Reis, Maria Vodovoz, Giovanni Gadda
d-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is a flavin-dependent oxidoreductase, which is part of a novel two-enzyme racemization system that functions to convert d-arginine to l-arginine. PaDADH contains a noncovalently linked FAD that shows the highest activity with d-arginine. The enzyme exhibits broad substrate specificity towards d-amino acids, particularly with cationic and hydrophobic d-amino acids. Biochemical studies have established the structure and the mechanistic properties of the enzyme...
June 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28623286/trait-choice-profoundly-affected-the-ecological-conclusions-drawn-from-functional-diversity-measures
#12
Linhai Zhu, Bojie Fu, Huoxing Zhu, Cong Wang, Lei Jiao, Ji Zhou
Although trait choice is crucial to quantify functional diversity appropriately, the quantitative methods for it are rarely compared and discussed. Meanwhile, very little is known about how trait choice affects ecological conclusions drawn from functional diversity measures. We presented the four methods of trait selection as alternatives to the ordination axis-based method, which directly identify a subset of key traits to represent the main variation of all the traits. To evaluate their performance, we compared the closeness of association obtained by different methods between species richness and functional diversity indices (FAD, FD, Q, FDis) in the six ecosystems...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619619/flavin-catalyzed-redox-tailoring-reactions-in-natural-product-biosynthesis
#13
REVIEW
Robin Teufel
Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e...
June 12, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28618182/mechanism-and-regulation-of-sorbicillin-biosynthesis-by-penicillium-chrysogenum
#14
Fernando Guzmán-Chávez, Oleksandr Salo, Yvonne Nygård, Peter P Lankhorst, Roel A L Bovenberg, Arnold J M Driessen
Penicillium chrysogenum is a filamentous fungus that is used to produce β-lactams at an industrial scale. At an early stage of classical strain improvement, the ability to produce the yellow-coloured sorbicillinoids was lost through mutation. Sorbicillinoids are highly bioactive of great pharmaceutical interest. By repair of a critical mutation in one of the two polyketide synthases in an industrial P. chrysogenum strain, sorbicillinoid production was restored at high levels. Using this strain, the sorbicillin biosynthesis pathway was elucidated through gene deletion, overexpression and metabolite profiling...
June 15, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28615448/structural-and-biochemical-analyses-reveal-insights-into-covalent-flavinylation-of-the-escherichia-coli-complex-ii-homolog-quinol-fumarate-reductase
#15
C A Starbird, Elena Maklashina, Pankaj Sharma, Susan Qualls-Histed, Gary Cecchini, T M Iverson
The Escherichia coli Complex II homolog quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of Complex II homologs, but the mechanisms underlying the covalent attachment of FAD remain to be fully elucidated. Here, we explored the mechanisms of covalent flavinylation of the E. coli QFR FrdA subunit. Using a ΔsdhE E. coli strain, we show that the requirement for the assembly factor depends on the cellular redox environment...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28611720/family-function-and-self-esteem-among-chinese-university-students-with-and-without-grandparenting-experience-moderating-effect-of-social-support
#16
Jingyu Shi, Lu Wang, Yuhong Yao, Na Su, Xudong Zhao, Chenyu Zhan
This study examines the association between family function and self-esteem of Chinese university students with grandparenting experience, and explores the moderating effects of social support in this link. Two thousand five hundred thirty university students (1372 males and 1158 females) from a Chinese university completed the Perceived Social Support Scale, the Rosenberg's Self-esteem Scale, and the Family Assessment Device (FAD). Six hundred and forty-five (25.69%) students reported grandparenting experience and they reported lower scores on self-esteem and social support than the students raised only by their parents...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28607049/crystal-structures-and-atomic-model-of-nadph-oxidase
#17
Francesca Magnani, Simone Nenci, Elisa Millana Fananas, Marta Ceccon, Elvira Romero, Marco W Fraaije, Andrea Mattevi
NADPH oxidases (NOXs) are the only enzymes exclusively dedicated to reactive oxygen species (ROS) generation. Dysregulation of these polytopic membrane proteins impacts the redox signaling cascades that control cell proliferation and death. We describe the atomic crystal structures of the catalytic flavin adenine dinucleotide (FAD)- and heme-binding domains of Cylindrospermum stagnale NOX5. The two domains form the core subunit that is common to all seven members of the NOX family. The domain structures were then docked in silico to provide a generic model for the NOX family...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28605577/a-toolkit-for-nannochloropsis-oceanica-ccmp1779-enables-gene-stacking-and-genetic-engineering-of-the-eicosapentaenoic-acid-pathway-for-enhanced-long-chain-polyunsaturated-fatty-acid-production
#18
Eric Poliner, Jane A Pulman, Krzysztof Zienkiewicz, Kevin Childs, Christoph Benning, Eva M Farré
Nannochloropsis oceanica is an oleaginous microalga rich in ω3long-chain polyunsaturated fatty acids (LC-PUFAs) content, in the form of eicosapentaenoic acid (EPA). We identified the enzymes involved in LC-PUFA biosynthesis in N. oceanica CCMP1779 and generated multigene expression vectors aiming at increasing LC-PUFA content in vivo. We isolated the cDNAs encoding four fatty acid desaturases (FAD) and determined their function by heterologous expression in S. cerevisiae. To increase the expression of multiple fatty acid desaturases in N...
June 12, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28604669/structural-and-mechanistic-basis-of-differentiated-inhibitors-of-the-acute-pancreatitis-target-kynurenine-3-monooxygenase
#19
Jonathan P Hutchinson, Paul Rowland, Mark R D Taylor, Erica M Christodoulou, Carl Haslam, Clare I Hobbs, Duncan S Holmes, Paul Homes, John Liddle, Damian J Mole, Iain Uings, Ann L Walker, Scott P Webster, Christopher G Mowat, Chun-Wa Chung
Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28602956/structure-function-studies-of-mical-the-unusual-multidomain-flavoenzyme-involved-in-actin-cytoskeleton-dynamics
#20
REVIEW
Maria Antonietta Vanoni
MICAL (from the Molecule Interacting with CasL) indicates a family of multidomain proteins conserved from insects to humans, which are increasingly attracting attention for their participation in the control of actin cytoskeleton dynamics, and, therefore, in the several related key processes in health and disease. MICAL is unique among actin binding proteins because it catalyzes a NADPH-dependent F-actin depolymerizing reaction. This unprecedented reaction is associated with its N-terminal FAD-containing domain that is structurally related to p-hydroxybenzoate hydroxylase, the prototype of aromatic monooxygenases, but catalyzes a strong NADPH oxidase activity in the free state...
June 8, 2017: Archives of Biochemistry and Biophysics
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