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https://www.readbyqxmd.com/read/28432298/endogenous-two-photon-excited-fluorescence-imaging-characterizes-neuron-and-astrocyte-metabolic-responses-to-manganese-toxicity
#1
Emily Stuntz, Yusi Gong, Disha Sood, Volha Liaudanskaya, Dimitra Pouli, Kyle P Quinn, Carlo Alonzo, Zhiyi Liu, David L Kaplan, Irene Georgakoudi
As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429324/photomovement-in-euglena
#2
Donat-P Häder, Mineo Iseki
Motile microorganisms such as the green Euglena gracilis use a number of external stimuli to orient in their environment. They respond to light with photophobic responses, photokinesis and phototaxis, all of which can result in accumulations of the organisms in suitable habitats. The light responses operate synergistically with gravitaxis, aerotaxis and other responses. Originally the microscopically obvious stigma was thought to be the photoreceptor, but later the paraxonemal body (PAB, paraflagellar body) has been identified as the light responsive organelle, located in the trailing flagellum inside the reservoir...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28427558/a-computational-approach-to-identify-the-biophysical-and-structural-aspects-of-methylenetetrahydrofolate-reductase-mthfr-mutations-a222v-e429a-and-r594q-leading-to-schizophrenia
#3
Himani Tanwar, P Sneha, D Thirumal Kumar, R Siva, Charles Emmanuel Jebaraj Walter, C George Priya Doss
The association between depression and methylenetetrahydrofolate reductase (MTHFR) has been continually demonstrated in clinical studies, yet there are sparse resources available to build a relationship between the mutations associated with MTHFR and depression. The common mutations found to be associated with schizophrenia and MTHFR are A222V, E429A, and R594Q. Although abundant research on structural and functional effects caused by A222V mutation is available, very less amount of studies have been done on the other two mutants (E429A and R594Q)...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28426977/blue-violet-laser-inactivates-methicillin-resistant-staphylococcus-aureus-by-altering-its-transmembrane-potential
#4
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/28425502/revealing-hidden-conformational-space-of-lov-protein-vivid-through-rigid-residue-scan-simulations
#5
Hongyu Zhou, Brian D Zoltowski, Peng Tao
VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421043/outlining-core-pathways-of-amyloid-toxicity-in-bacteria-with-the-repa-wh1-prionoid
#6
Laura Molina-García, María Moreno-Del Álamo, Pedro Botias, Zaira Martín-Moldes, María Fernández, Alicia Sánchez-Gorostiaga, Aída Alonso-Del Valle, Juan Nogales, Jesús García-Cantalejo, Rafael Giraldo
The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible amyloid proteinopathy in Escherichia coli that inhibits growth and eventually kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through model lipid membranes, suggesting a possible mechanism for bacterial cell death. By comparing acutely (A31V) and mildly (ΔN37) cytotoxic mutant variants of the protein, we report here that RepA-WH1(A31V) expression decreases the intracellular osmotic pressure and compromise bacterial viability under either aerobic or anaerobic conditions...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#7
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28406895/the-superfamily-keeps-growing-identification-in-trypanosomatids-of-ribj-the-first-riboflavin-transporter-family-in-protists
#8
Darío E Balcazar, María Cristina Vanrell, Patricia S Romano, Claudio A Pereira, Fernando A Goldbaum, Hernán R Bonomi, Carolina Carrillo
BACKGROUND: Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28404662/slc25-family-member-genetic-interactions-identify-a-role-for-hem25-in-yeast-electron-transport-chain-stability
#9
J Noelia Dufay, J Pedro Fernández-Murray, Christopher R McMaster
The SLC25 family member SLC25A38 (Hem25 in yeast) was recently identified as a mitochondrial glycine transporter that provides substrate to initiate heme/hemoglobin synthesis. Mutations in the human SLC25A38 gene cause congenital sideroblastic anemia. The full extent to which SLC25 family members co-regulate heme synthesis with other mitochondrial functions is not clear. In this study, we surveyed 29 non-essential SLC25 family members in Saccharomyces cerevisiae for their ability to support growth in the presence and absence of HEM25...
April 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28402850/fad-regulates-cryptochrome-protein-stability-and-circadian-clock-in-mice
#10
Arisa Hirano, Daniel Braas, Ying-Hui Fu, Louis J Ptáček
The circadian clock generates biological rhythms of metabolic and physiological processes, including the sleep-wake cycle. We previously identified a missense mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2 (CRY2), a clock protein that causes human advanced sleep phase. This prompted us to examine the role of FAD as a mediator of the clock and metabolism. FAD stabilized CRY proteins, leading to increased protein levels. In contrast, knockdown of Riboflavin kinase (Rfk), an FAD biosynthetic enzyme, enhanced CRY degradation...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28398039/influence-of-humidity-on-grip-and-release-adhesion-mechanisms-for-gecko-inspired-microfibrillar-surfaces
#11
Nicholas Cadirov, Jamie A Booth, Kimberly L Turner, Jacob N Israelachvili
Geckos have developed foot pads that allow them to maintain their unique climbing ability despite vast differences of surfaces and environments, from dry desert to humid rainforest. Likewise, successful gecko-inspired mimics should exhibit adhesive and frictional performance across a similarly diverse range of climates. In this work, we focus on the effect of relative humidity (RH) on the "frictional-adhesion" behavior of gecko-inspired adhesive pads. A surface forces apparatus was used to quantitatively measure adhesion and friction forces of a microfibrillar cross-linked polydimethylsiloxane surface against a smooth hemispherical glass disk at varying relative humidity, from 0 to 100% (including fully submerged under water)...
April 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28397795/the-structure-of-lactococcus-lactis-thioredoxin-reductase-reveals-molecular-features-of-photo-oxidative-damage
#12
Nicklas Skjoldager, Maria Blanner Bang, Martin Rykær, Olof Björnberg, Michael J Davies, Birte Svensson, Pernille Harris, Per Hägglund
The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395750/efficacy-and-safety-of-a-new-spot-on-formulation-of-selamectin-plus-sarolaner-in-the-treatment-of-naturally-occurring-flea-and-tick-infestations-in-cats-presented-as-veterinary-patients-in-europe
#13
RANDOMIZED CONTROLLED TRIAL
Thomas Geurden, Csilla Becskei, Robert Farkas, Dan Lin, Douglas Rugg
Two randomised, blinded, multi-centre field studies were conducted in Europe (Germany, Italy, France, Hungary) to demonstrate the efficacy and safety of three monthly applications of a new spot-on formulation of selamectin plus sarolaner (Stronghold(®) Plus, Zoetis) against natural flea or tick infestations in cats presented as veterinary patients. The spot-on formulation was administered at the commercial dose range of 6.0-12.0mg selamectin and 1.0-2.0mg sarolaner per kg bodyweight. In the flea study, the improvement in clinical signs associated with flea allergy dermatitis (FAD) was also monitored...
April 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28394779/evaluating-new-skill-sets-for-performance-improvement-human-factors-as-a-case-study
#14
T Eugene Day, Sarah Henrickson Parker, Virginia Lederman, Debbie McKetta, Anna Spraycar
New skill sets and improvement disciplines are constantly arising across the vast industrial and academic landscape of modern economies. Prescient hospital administrators are routinely searching for new and innovative ways to improve care, care delivery, safety, quality, and access. But, it can be challenging to identify those emerging skill sets, which will likely have lasting effect and will provide strong return on investment, from passing fads with little capacity to move performance benchmarks for a hospital...
April 7, 2017: Health Care Manager
https://www.readbyqxmd.com/read/28393489/grouped-factors-of-the-ssade-signs-and-symptoms-accompanying-dementia-while-eating-and-nutritional-status-an-analysis-of-older-people-receiving-nutritional-care-in-long-term-care-facilities-in-japan
#15
Kento Takada, Kazumi Tanaka, Mihoko Hasegawa, Michiko Sugiyama, Nobuo Yoshiike
BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are very common among older people, and previous studies showed that BPSD affects eating behaviour negatively, possibly resulting in undernutrition. In a previous study, we constructed a set of 11 items based on direct observations of older people with dementia during mealtime and named them 'SSADE: signs and symptoms accompanying dementia while eating'. AIMS: This study aimed to conduct a factor analysis to clarify the structure of the set of 11 SSADE items and to analyse the relationship of the SSADE with nutritional status...
April 9, 2017: International Journal of Older People Nursing
https://www.readbyqxmd.com/read/28393477/residues-at-a-single-site-differentiate-animal-cryptochromes-from-cyclobutane-pyrimidine-dimer-photolyases-by-affecting-the-proteins-preferences-for-reduced-fad
#16
Lei Xu, Bin Wen, Yuan Wang, Changqing Tian, Mingcai Wu, Guoping Zhu
Cryptochromes (CRYs) and photolyases belong to the cryptochrome/photolyase family (CPF). Reduced FAD is essential for photolyases to photorepair UV induced cyclobutane pyrimidine dimers (CPDs) or 6-4 photoproducts in DNA. In Drosophila CRY (dCRY, a type I animal CRY), FAD is converted to the anionic radical but not to the reduced state during illumination, which may induce a conformational change in the protein to relay the light signal downstream. To explore the foundation of these differences, multiple sequence alignment of 650 CPF protein sequences was performed...
April 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28389477/efad-transgenic-mice-as-a-human-apoe-relevant-preclinical-model-of-alzheimer-s-disease
#17
Leon M Tai, Deebika Balu, Evangelina Avila-Munoz, Laila Abdullah, Riya Thomas, Nicole Collins, Ana Carolina Valencia-Olvera, Mary Jo LaDu
Identified in 1993, APOE4 is the greatest genetic risk factor for sporadic Alzheimers disease (AD), increasing risk up to 12-fold compared to APOE3, with APOE2 decreasing AD risk. However, the functional effects of APOE4 on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOE genotypes effect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)-APOE. The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid beta deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits...
April 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28377716/human-cytochrome-p450-3a4-as-a-biocatalyst-effects-of-the-engineered-linker-in-modulation-of-coupling-efficiency-in-3a4-bmr-chimeras
#18
Danilo Degregorio, Serena D'Avino, Silvia Castrignanò, Giovanna Di Nardo, Sheila J Sadeghi, Gianluca Catucci, Gianfranco Gilardi
Human liver cytochrome P450 3A4 is the main enzyme involved in drug metabolism. This makes it an attractive target for biocatalytic applications, such as the synthesis of pharmaceuticals and drug metabolites. However, its poor solubility, stability and low coupling have limited its application in the biotechnological context. We previously demonstrated that the solubility of P450 3A4 can be increased by creating fusion proteins between the reductase from Bacillus megaterium BM3 (BMR) and the N-terminally modified P450 3A4 (3A4-BMR)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28374822/genome-wide-identification-of-membrane-bound-fatty-acid-desaturase-genes-in-gossypium-hirsutum-and-their-expressions-during-abiotic-stress
#19
Jiyu Feng, Yating Dong, Wei Liu, Qiuling He, M K Daud, Jinhong Chen, Shuijin Zhu
Membrane-bound fatty acid desaturases (FADs) are of great importance and play multiple roles in plant growth and development. In the present study, 39 full-length FAD genes, based on database searches, were identified in tetraploid upland cotton (Gossypium hirsutum L.) and were phylogenetically clustered into four subfamilies. Genomic localization revealed that 34 genes were mapped on 22 chromosomes, and five genes were positioned on the scaffold sequences. The FAD genes of G. hirsutum in the same subfamily had similar gene structures...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373637/cytoprotective-effects-and-mechanisms-of-%C3%AE-17-fatty-acid-desaturase-in-injured-human-umbilical-vein-endothelial-cells-huvecs
#20
Haoyu Zhou, Chengming Wang
BACKGROUND The beneficial effect of Δ-17 FAD is poorly understood. The aim of this study was to investigate the protective mechanism of fatty acids against atherosclerotic (AS) damage induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs), and to identify the molecular mechanisms involved. MATERIAL AND METHODS The ox-LDL was used to induce lipotoxicity in HUVECs to establish a model of oxidative injury. HUVECs were transfected with Δ-17FAD lentivirus to induce cytoprotective effects...
April 4, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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