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https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#1
Shihui Liu, Qian Ma, Rasem Fattah, Thomas H Bugge, Stephen H Leppla
Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease having MEKs as targets. LF relies on the cell-binding B-subunit, protective antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell surface toxin receptors and is activated by furin protease to form an LF-binding-competent oligomer-PA pre-pore, which converts to a functional protein-conductive pore in the acidic endocytic vesicles, allowing translocation of LF into the cytosol...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533388/selective-lowering-of-synapsins-induced-by-oligomeric-%C3%AE-synuclein-exacerbates-memory-deficits
#2
Megan E Larson, Susan J Greimel, Fatou Amar, Michael LaCroix, Gabriel Boyle, Mathew A Sherman, Hallie Schley, Camille Miel, Julie A Schneider, Rakez Kayed, Fabio Benfenati, Michael K Lee, David A Bennett, Sylvain E Lesné
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531139/dual-component-gelatinous-peptide-reactive-oligomer-formulations-as-conduit-material-and-luminal-filler-for-peripheral-nerve-regeneration
#3
Caroline Kohn-Polster, Divya Bhatnagar, Derek J Woloszyn, Matthew Richtmyer, Annett Starke, Alexandra H Springwald, Sandra Franz, Michaela Schulz-Siegmund, Hilton M Kaplan, Joachim Kohn, Michael C Hacker
Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility...
May 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28528849/extracellular-low-n-oligomers-of-tau-cause-selective-synaptotoxicity-without-affecting-cell-viability
#4
Senthilvelrajan Kaniyappan, Ram Reddy Chandupatla, Eva-Maria Mandelkow, Eckhard Mandelkow
INTRODUCTION: Tau-mediated toxicity in Alzheimer's disease is thought to operate through low-n oligomers, rather than filamentous aggregates. However, the nature of oligomers and pathways of toxicity are poorly understood. Therefore, we investigated structural and functional aspects of highly purified oligomers of a pro-aggregant tau species. METHODS: Purified oligomers of the tau repeat domain were characterized by biophysical and structural methods. Functional aspects were investigated by cellular assays ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) bromide assay of cell viability, lactate dehydrogenase release assay [for cell toxicity], reactive oxygen species production, and calcium assay), combined with analysis of neuronal dendritic spines exposed to oligomers...
May 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28528551/robust-bipolar-light-emission-and-charge-transport-in-symmetric-molecular-junctions
#5
Ushula M Tefashe, Quyen Nguyen, Frederic Lafolet, Jean-Christophe Lacroix, Richard L McCreery
Molecular junctions consisting of a Ru(bpy)3 oligomer between conducting carbon contacts exhibit an exponential dependence of junction current on molecular layer thickness (d) similar to that observed for other aromatic devices when d<4 nm. However, when d exceeds 4 nm a change in transport mechanism occurs which coincides with light emission in the range of 600-900 nm. Unlike light emission from electrochemical cells or solid-state films con-taining Ru(bpy)3, emission is bipolar, occurs in vacuum, has rapid rise time (<5 msec), and persists for more than 10 hours...
May 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28528194/analysis-of-peg-oligomers-in-black-gel-inks-discrimination-and-ink-dating
#6
Qiran Sun, Yiwen Luo, Ping Xiang, Xu Yang, Min Shen
Carbon-based black gel inks are common samples in forensic practice of questioned document examination in China, but there are few analytical methods for this type of ink. In this study, a liquid chromatography-.high resolution mass spectrometry (LC-HRMS) method was established for the analysis of PEG oligomers in carbon-based black gel ink entries. The coupled instruments achieve both the identification and quantification of PEG oligomers in ink entries with reproducible results. Twenty carbon-based black gel inks, whose Raman spectra appeared identical, were analyzed using the LC-HRMS method...
May 4, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28527888/tetrameric-structure-of-the-flagellar-cap-protein-flid-from-serratia-marcescens
#7
So Yeon Cho, Wan Seok Song, Ho Jeong Hong, Geun-Shik Lee, Seung Goo Kang, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Sung-Il Yoon
Bacterial motility is provided by the flagellum. FliD is located at the distal end of the flagellum and plays a key role in the insertion of each flagellin protein at the growing tip of the flagellar filament. Because FliD functions as an oligomer, the determination of the oligomeric state of FliD is critical to understanding the molecular mechanism of FliD-mediated flagellar growth. FliD has been shown to adopt a pentameric or a hexameric structure depending on the bacterial species. Here, we report another distinct oligomeric form of FliD based on structural and biochemical studies...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28527708/cortical-cytoskeleton-dynamics-regulates-plasma-membrane-calcium-atpase-isoform-2-pmca2-activity
#8
Marianela G Dalghi, Mariela Ferreira-Gomes, Nicolás Montalbetti, Alexandre Simonin, Emanuel E Strehler, Matthias A Hediger, Juan Pablo Rossi
We have previously shown that purified actin can directly bind to human plasma membrane Ca(2+) ATPase 4b (hPMCA4b) and exert a dual modulation on its Ca(2+)-ATPase activity: F-actin inhibits PMCA while short actin oligomers may contribute to PMCA activation. These studies had to be performed with purified proteins given the nature of the biophysical and biochemical approaches used. To assess whether a functional interaction between the PMCAs and the cortical cytoskeleton is of physiological relevance, we characterized this phenomenon in the context of a living cell by monitoring in real-time the changes in the cytosolic calcium levels ([Ca(2+)]CYT)...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527631/the-thiol-switch-c684-in-mitofusin-2-mediates-redox-induced-alterations-of-mitochondrial-shape-and-respiration
#9
Osamah Thaher, Christina Wolf, Partha Narayan Dey, Alireza Pouya, Verena Wüllner, Stefan Tenzer, Axel Methner
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28527593/a-structural-and-functional-study-of-gln147-deamidation-in-%C3%AE-a-crystallin-a-major-site-of-modification-in-human-cataract
#10
Nicholas J Ray, Damien Hall, John A Carver
Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin protein unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering...
May 17, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28527458/conformation-change-of-an-isotactic-poly-n-isopropylacrylamide-membrane-molecular-dynamics
#11
Irene Adroher-Benítez, Arturo Moncho-Jordá, Gerardo Odriozola
In this work, isotactic Poly (N-Isopropylacrylamide)-PNIPAM-in neat water and in electrolyte solutions is studied by means of molecular dynamics simulations. This is done for an infinitely diluted oligomer and for an assembly of several PNIPAM chains arranged into a planar membrane configuration with a core-shell morphology. We employed two different force fields, AMBER (assisted model building with energy refinement) and OPLS-AA (all atom - optimized potentials for liquid simulations) in combination with extended simple point charge water...
May 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28527208/neuronal-expression-of-truncated-tau-efficiently-promotes-neurodegeneration-in-animal-models-pitfalls-of-toxic-oligomer-analysis
#12
Rostislav Skrabana, Branislav Kovacech, Peter Filipcik, Norbert Zilka, Santosh Jadhav, Tomas Smolek, Eva Kontsekova, Michal Novak
Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development. Here we highlight common features of truncated tau models and make a critical assessment of possible pitfalls in their analysis. Particularly, the amount of soluble tau oligomers, which are suspected to be neurotoxic agents participating on the spreading of pathology inside the brain, may be overestimated due to a post-lysis oxidative tau oligomerization...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28526816/delineation-of-b-cell-epitopes-of-salmonella-enterica-serovar-typhi-hemolysin-e-potential-antibody-therapeutic-target
#13
Chai Fung Chin, Jing Yi Lai, Yee Siew Choong, Amy Amilda Anthony, Asma Ismail, Theam Soon Lim
Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521637/the-receptor-like-cytoplasmic-kinase-bsr1-mediates-chitin-induced-defense-signaling-in-rice-cells
#14
Yasukazu Kanda, Naoki Yokotani, Satoru Maeda, Yoko Nishizawa, Takashi Kamakura, Masaki Mori
Broad-Spectrum Resistance 1 (BSR1) encodes a rice receptor-like cytoplasmic kinase, and enhances disease resistance when overexpressed. Rice plants overexpressing BSR1 are highly resistant to diverse pathogens, including rice blast fungus. However, the mechanism responsible for this resistance has not been fully characterized. To analyze the BSR1 function, BSR1-knockout (BSR1-KO) plants were generated using a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system...
May 18, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28520783/effect-of-n-terminal-region-of-nuclear-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-on-function-and-quaternary-structure
#15
Mohamed Taha Moutaoufik, Geneviève Morrow, Stéphanie Finet, Robert M Tanguay
The importance of the N-terminal region (NTR) in the oligomerization and chaperone-like activity of the Drosophila melanogaster small nuclear heat shock protein DmHsp27 was investigated by mutagenesis using size exclusion chromatography and native gel electrophoresis. Mutation of two sites of phosphorylation in the N-terminal region, S58 and S75, did not affect the oligomerization equilibrium or the intracellular localization of DmHsp27 when transfected into mammalian cells. Deletion or mutation of specific residues within the NTR region delineated a motif (FGFG) important for the oligomeric structure and chaperone-like activity of this sHsp...
2017: PloS One
https://www.readbyqxmd.com/read/28520455/quantitative-determination-of-avi-7100-radavirsen-a-phosphorodiamidate-morpholino-oligomer-pmoplus-%C3%A2-in-human-plasma-using-lc-ms-ms
#16
Min Meng, Jianbo Zhang, Aihua Liu, Scott Reuschel, Pete Sazani, Michael Wong
AIM: AVI-7100 (Radavirsen) is a 20-mer phosphorodiamidate morpholino oligomer (PMOplus®) for the treatment of influenza. Results/methodology: An automated solid-phase extraction method was used to extract plasma samples (200 μl). The extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry under the positive ionization mode. This method was fully validated over the calibration curve range of 5.00-1000 ng/ml. The between-run precision and accuracy ranged from 0...
May 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28519902/reduced-gliotransmitter-release-from-astrocytes-mediates-tau-induced-synaptic-dysfunction-in-cultured-hippocampal-neurons
#17
Roberto Piacentini, Domenica Donatella Li Puma, Marco Mainardi, Giacomo Lazzarino, Barbara Tavazzi, Ottavio Arancio, Claudio Grassi
Tau is a microtubule-associated protein exerting several physiological functions in neurons. In Alzheimer's disease (AD) misfolded tau accumulates intraneuronally and leads to axonal degeneration. However, tau has also been found in the extracellular medium. Recent studies indicated that extracellular tau uploaded from neurons causes synaptic dysfunction and contributes to tau pathology propagation. Here we report novel evidence that extracellular tau oligomers are abundantly and rapidly accumulated in astrocytes where they disrupt intracellular Ca(2+) signaling and Ca(2+) -dependent release of gliotransmitters, especially ATP...
May 18, 2017: Glia
https://www.readbyqxmd.com/read/28517932/mechanism-of-discrimination-of-8-oxoguanosine-versus-guanosine-by-e-coli-fpg
#18
Namrata Jayanth, Mrinalini Puranik
The mutagenic 8-oxoguanosine monophosphate 1, the predominant product of DNA oxidation, is excised by formamidopyrimidine glycosylase (Fpg) in bacteria. The mechanism of recognition of 8-oxodG, which differs subtly from its normal counterpart, guanosine monophosphate (dG), by E. coli Fpg remains elusive due to the lack of structural data of E. coli Fpg bound to 8-oxodG. Here, we present solution-state structure of 8-oxodG oligomer bound to E. coli E3Q Fpg using UV resonance Raman (UVRR) spectroscopy. The vibrational spectra report on the π-stacking and hydrogen bonding interactions established by 8-oxodG with E...
May 18, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28517926/laser-induced-population-inversion-in-rhodamine-6g-for-lysozyme-oligomers-detection
#19
Piotr Hanczyc, Lech Sznitko
Fluorescence spectroscopy is a common method for detecting amyloid fibrils where organic fluorophores are used as markers that exhibit increase of the quantum yield upon binding. However, most of the dyes exhibit enhanced emission only when bound to mature fibrils and significantly weaker signals are obtained in presence of amyloid oligomers. In the concept of population inversion, laser is used as an excitation source in order to keep the major fraction of molecules in the excited state to create the pathways for stimulated emission occurrence...
May 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28516950/high-conductance-values-in-%C3%AF-folded-molecular-junctions
#20
Marco Carini, Marta P Ruiz, Imanol Usabiaga, José A Fernández, Emilio J Cocinero, Manuel Melle-Franco, Ismael Diez-Perez, Aurelio Mateo-Alonso
Folding processes play a crucial role in the development of function in biomacromolecules. Recreating this feature on synthetic systems would not only allow understanding and reproducing biological functions but also developing new functions. This has inspired the development of conformationally ordered synthetic oligomers known as foldamers. Herein, a new family of foldamers, consisting of an increasing number of anthracene units that adopt a folded sigmoidal conformation by a combination of intramolecular hydrogen bonds and aromatic interactions, is reported...
May 18, 2017: Nature Communications
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