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https://www.readbyqxmd.com/read/28099487/metabolic-imaging-of-head-and-neck-cancer-organoids
#1
Amy T Shah, Tiffany M Heaster, Melissa C Skala
Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model...
2017: PloS One
https://www.readbyqxmd.com/read/28098177/an-extended-n-h-bond-driven-by-a-conserved-second-order-interaction-orients-the-flavin-n5-orbital-in-cholesterol-oxidase
#2
Emily Golden, Li-Juan Yu, Flora Meilleur, Matthew P Blakeley, Anthony P Duff, Amir Karton, Alice Vrielink
The protein microenvironment surrounding the flavin cofactor in flavoenzymes is key to the efficiency and diversity of reactions catalysed by this class of enzymes. X-ray diffraction structures of oxidoreductase flavoenzymes have revealed recurrent features which facilitate catalysis, such as a hydrogen bond between a main chain nitrogen atom and the flavin redox center (N5). A neutron diffraction study of cholesterol oxidase has revealed an unusual elongated main chain nitrogen to hydrogen bond distance positioning the hydrogen atom towards the flavin N5 reactive center...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095314/cloning-and-expression-characterization-of-peroxisome-proliferator-activated-receptors-ppars-with-their-agonists-dietary-lipids-and-ambient-salinity-in-rabbitfish-siganus-canaliculatus
#3
Cuihong You, Danli Jiang, Qinghao Zhang, Dizhi Xie, Shuqi Wang, Yewei Dong, Yuanyou Li
Rabbitfish Siganus canaliculatus is the first marine teleost reported to have the ability of biosynthesizing C20-22 long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors, and thus provides us a model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. To investigate the possible roles of peroxisome proliferator-activated receptors (PPARs), critical transcription factors involved in the regulation of lipid metabolism, in the regulation of LC-PUFA biosynthesis in rabbitfish, the PPAR genes were cloned and their expression characterization with PPAR agonists, dietary lipid resource, and ambient salinity were examined...
January 14, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28092081/epigenetics-in-alzheimer-s-disease-perspective-of-dna-methylation
#4
REVIEW
Talal Jamil Qazi, Zhenzhen Quan, Asif Mir, Hong Qing
Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28091661/biochemical-characterization-of-the-selenoproteome-in-gallus-gallus-via-bioinformatics-analysis-structure-function-relationships-and-interactions-of-binding-molecules
#5
Shi-Yong Zhu, Xue-Nan Li, Xiao-Chen Sun, Jia Lin, Wei Li, Cong Zhang, Jin-Long Li
Knowledge about mammalian selenoproteins is increasing. However, the selenoproteome of birds remains considerably less understood, especially concerning its biochemical characterization, structure-function relationships and the interactions of binding molecules. In this work, the SECIS elements, subcellular localization, protein domains and interactions of binding molecules of the selenoproteome in Gallus gallus were analyzed using bioinformatics tools. We carried out comprehensive analyses of the structure-function relationships and interactions of the binding molecules of selenoproteins, to provide biochemical characterization of the selenoproteome in Gallus gallus...
January 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28065867/cloning-expression-purification-and-biophysical-analysis-of-two-putative-halogenases-from-the-glycopeptide-a47-934-gene-cluster-of-streptomyces-toyocaensis
#6
Tabata P Cardoso, Larissa A de Sá, Priscila Dos S Bury, Sair M Chavez-Pacheco, Marcio V B Dias
Glycopeptides are an important class of antibiotics used in the treatment of several infections, including those caused by methicillin resistant Staphylococcus aureus. Glycopeptides are biosynthesized by a Non Ribosomal Peptide Synthase (NRPS) and the resulting peptide precursors are decorated by several tailoring enzymes, such as halogenases and glycosyltransferases. These enzymes are important targets of protein engineering to produce new derivatives of known antibiotics. Herein we show the production of two putative halogenases, denominated StaI and StaK, involved in the biosynthesis of the glycopeptide A47,934 in Streptomyces toyocaensis NRRL 15,009...
January 5, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28063999/relationship-between-intracellular-ph-metabolic-co-factors-and-caspase-3-activation-in-cancer-cells-during-apoptosis
#7
Tatiana F Sergeeva, Marina V Shirmanova, Olga A Zlobovskaya, Alena I Gavrina, Varvara V Dudenkova, Maria M Lukina, Konstantin A Lukyanov, Elena V Zagaynova
A complex cascade of molecular events occurs in apoptotic cells but cell-to-cell variability significantly complicates determination of the order and interconnections between different processes. For better understanding of the mechanisms of programmed cell death, dynamic simultaneous registration of several parameters is required. In this paper we used multiparameter fluorescence microscopy to analyze energy metabolism, intracellular pH and caspase-3 activation in living cancer cells in vitro during staurosporine-induced apoptosis...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28062077/breakfast-and-behavior-in-morning-tasks-facts-or-fads
#8
REVIEW
Valeria Edefonti, Francesca Bravi, Monica Ferraroni
BACKGROUND: Most of the studies investigating the effects of breakfast on cognitive performance have compared performance in subjects who have or have not consumed this meal. However, characteristics of breakfast itself may influence mental abilities. Moreover, as far as the positive effects of having breakfast is more evident, research may focus on the specific characteristics of an adequate breakfast. METHODS: To update an existing systematic review, published at the beginning of 2014, on the role of nutrient composition and/or energy intake at breakfast on the accomplishment of school-related tasks and cognition, we carried out a systematic review of the literature through PUBMED database...
December 24, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28059861/effect-of-threatening-life-experiences-and-adverse-family-relations-in-ulcerative-colitis-analysis-using-structural-equation-modeling-and-comparison-with-crohn-s-disease
#9
Vered Slonim-Nevo, Orly Sarid, Michael Friger, Doron Schwartz, Ruslan Sergienko, Avihu Pereg, Hillel Vardi, Terri Singer, Elena Chernin, Dan Greenberg, Shmuel Odes
BACKGROUND AND AIMS: We published that threatening life experiences and adverse family relations impact Crohn's disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC). PATIENTS AND METHODS: Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE)...
January 4, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28052125/biosynthesis-of-polyunsaturated-fatty-acids-in-sea-urchins-molecular-and-functional-characterisation-of-three-fatty-acyl-desaturases-from-paracentrotus-lividus-lamark-1816
#10
Naoki Kabeya, Alicia Sanz-Jorquera, Stefano Carboni, Andrew Davie, Angela Oboh, Oscar Monroig
Sea urchins are broadly recognised as a delicacy and their quality as food for humans is highly influenced by their diet. Lipids in general and the long-chain polyunsaturated fatty acids (LC-PUFA) in particular, are essential nutrients that determine not only the nutritional value of sea urchins but also guarantee normal growth and reproduction in captivity. The contribution of endogenous production (biosynthesis) of LC-PUFA in sea urchins remained unknown. Using Paracentrotus lividus as our model species, we aimed to characterise both molecularly and functionally the repertoire of fatty acyl desaturases (Fads), key enzymes in the biosynthesis of LC-PUFA, in sea urchins...
2017: PloS One
https://www.readbyqxmd.com/read/28049728/familial-alzheimer-s-disease-mutations-within-the-amyloid-precursor-protein-alter-the-aggregation-and-conformation-of-the-amyloid-beta-peptide
#11
Asa Hatami, Sanaz Monjazeb, Saskia Milton, Charles G Glabe
Most cases of Alzheimer's disease (AD) are sporadic, while a small percentage of AD cases, called familial AD (FAD), are associated with mutations in presinilins 1 and 2 and the amyloid precursor protein (APP). APP mutations falling within the Aβ sequence lead to a wide range of disease phenotypes. There is increasing evidence that distinct amyloid structures distinguished by amyloid conformation-dependent monoclonal antibodies have varying roles in pathology. It is possible that the phenotypic diversity of FAD associated with mutations within the Aβ sequence is due to differences in the conformations adopted by mutant Aβ peptides...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28048767/su-f-i-77-radiation-dose-in-cardiac-catheterization-procedures-impact-of-a-systematic-reduction-in-pulsed-fluoroscopy-frame-rate
#12
C Schultz, S Dixon
PURPOSE: To evaluate whether one small systematic reduction in fluoroscopy frame rate has a significant effect on the total air kerma and/or dose area product for diagnostic and interventional cardiac catheterization procedures. METHODS: The default fluoroscopy frame rate (FFR) was lowered from 15 to 10 fps in 5 Siemens™ Axiom Artis cardiac catheterization labs (CCL) on July 1, 2013. A total of 7212 consecutive diagnostic and interventional CCL procedures were divided into two study groups: 3602 procedures from 10/1/12 -6/30/13 with FFR of 15 fps; and 3610 procedures 7/1/13 - 3/31/14 at 10 fps...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28034781/increased-susceptibility-to-a%C3%AE-toxicity-in-neuronal-cultures-derived-from-familial-alzheimer-s-disease-psen1-a246e-induced-pluripotent-stem-cells
#13
Enrique Armijo, Cesar Gonzalez, Mohammad Shahnawaz, Andrea Flores, Brian Davis, Claudio Soto
Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients...
December 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28032983/two-flavoenzymes-catalyze-the-post-translational-generation-of-5-chlorotryptophan-and-2-aminovinyl-cysteine-during-nai-107-biosynthesis
#14
Manuel A Ortega, Dillon P Cogan, Subha Mukherjee, Neha Garg, Bo Li, Gabrielle N Thibodeaux, Sonia I Maffioli, Stefano Donadio, Margherita Sosio, Jerome Escano, Leif Smith, Satish K Nair, Wilfred A van der Donk
Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides containing thioether rings. In addition to these cross-links, the clinical candidate lantibiotic NAI-107 also possesses a C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) and a unique 5-chloro-l-tryptophan (ClTrp) moiety linked to its potent bioactivity. Bioinformatic and genetic analyses on the NAI-107 biosynthetic gene cluster identified mibH and mibD as genes encoding flavoenzymes responsible for the formation of ClTrp and AviCys, respectively...
January 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28025715/alzheimer-s-disease-experimental-models-and-reality
#15
REVIEW
Eleanor Drummond, Thomas Wisniewski
Experimental models of Alzheimer's disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor...
December 26, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28024938/severe-fluoropyrimidine-toxicity-due-to-novel-and-rare-dpyd-missense-mutations-deletion-and-genomic-amplification-affecting-dpd-activity-and-mrna-splicing
#16
André B P van Kuilenburg, Judith Meijer, Dirk Maurer, Doreen Dobritzsch, Rutger Meinsma, Maartje Los, Lia C Knegt, Lida Zoetekouw, Rob L H Jansen, Vincent Dezentjé, Lieke H van Huis-Tanja, Roel J W van Kampen, Jens Michael Hertz, Raoul C M Hennekam
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Genetic variations in DPD have emerged as predictive risk factors for severe fluoropyrimidine toxicity. Here, we report novel and rare genetic variants underlying DPD deficiency in 9 cancer patients presenting with severe fluoropyrimidine-associated toxicity. All patients possessed a strongly reduced DPD activity, ranging from 9 to 53% of controls. Analysis of the DPD gene (DPYD) showed the presence of 21 variable sites including 4 novel and 4 very rare aberrations: 3 missense mutations, 2 splice-site mutations, 1 intronic mutation, a deletion of 21 nucleotides and a genomic amplification of exons 9-12...
December 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28003863/resolving-contributions-of-oxygen-consuming-and-ros-generating-enzymes-at-the-synapse
#17
Engy A Abdel-Rahman, Ali M Mahmoud, Abdullah Aaliya, Yasmine Radwan, Basma Yasseen, Abdelrahman Al-Okda, Ahmed Atwa, Eslam Elhanafy, Moaaz Habashy, Sameh S Ali
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28000978/co-immobilized-phosphorylated-cofactors-and-enzymes-as-self-sufficient-heterogeneous-biocatalysts-for-chemical-processes
#18
Susana Velasco-Lozano, Ana I Benítez-Mateos, Fernando López-Gallego
Enzyme cofactors play a major role in biocatalysis, as many enzymes require them to catalyze highly valuable reactions in organic synthesis. However, the cofactor recycling is often a hurdle to implement enzymes at the industrial level. The fabrication of heterogeneous biocatalysts co-immobilizing phosphorylated cofactors (PLP, FAD(+) , and NAD(+) ) and enzymes onto the same solid material is reported to perform chemical reactions without exogeneous addition of cofactors in aqueous media. In these self-sufficient heterogeneous biocatalysts, the immobilized enzymes are catalytically active and the immobilized cofactors catalytically available and retained into the solid phase for several reaction cycles...
December 21, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27997715/structural-mechanism-for-bacterial-oxidation-of-oceanic-trimethylamine-into-trimethylamine-n-oxide
#19
Chun-Yang Li, Xiu-Lan Chen, Dian Zhang, Peng Wang, Qi Sheng, Ming Peng, Bin-Bin Xie, Qi-Long Qin, Ping-Yi Li, Xi-Ying Zhang, Hai-Nan Su, Xiao-Yan Song, Mei Shi, Bai-Cheng Zhou, Lu-Ying Xun, Yin Chen, Yu-Zhong Zhang
Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm...
December 20, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27995309/characterization-of-three-pyranose-dehydrogenase-isoforms-from-the-litter-decomposing-basidiomycete-leucoagaricus-meleagris-syn-agaricus-meleagris
#20
Michael M H Graf, Sandra Weber, Daniel Kracher, Roman Kittl, Christoph Sygmund, Roland Ludwig, Clemens Peterbauer, Dietmar Haltrich
Multigenicity is commonly found in fungal enzyme systems, with the purpose of functional compensation upon deficiency of one of its members or leading to enzyme isoforms with new functionalities through gene diversification. Three genes of the flavin-dependent glucose-methanol-choline (GMC) oxidoreductase pyranose dehydrogenase (AmPDH) were previously identified in the litter-degrading fungus Agaricus (Leucoagaricus) meleagris, of which only AmPDH1 was successfully expressed and characterized. The aim of this work was to study the biophysical and biochemical properties of AmPDH2 and AmPDH3 and compare them with those of AmPDH1...
December 19, 2016: Applied Microbiology and Biotechnology
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