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https://www.readbyqxmd.com/read/28107633/binding-and-proton-blockage-by-amantadine-variants-of-the-influenza-m2wt-and-m2s31n-explained
#1
Christina Tzitzoglaki, Anna K Wright, Kathrin-Maria Freudenberger, Anja Hoffmann, Ian Tietjen, Ioannis Stylianakis, Felix Kolarov, David Fedida, Michaela Schmidtke, Guenter Gauglitz, Timothy A Cross, Antonios Kolocouris
While aminoadamantanes are well-established inhibitors of the influenza A M2 proton channel, the mechanisms by which they are rendered ineffective against M2S31N are unclear. Solid state NMR, isothermal titration calorimetry, electrophysiology, anti-viral assays and molecular dynamics simulations suggest stronger binding interactions for aminoadamantanes to M2WT compared to negligible or weak binding to M2S31N. This is due to reshaping of the M2pore when N31 is present, which in contrast to WT, leads: A) to the loss of the V27 pocket for the adamantyl cage and to a predominant orientation of the ligand's ammonium group toward the N-terminus and, B) to the lack of a helical kink upon ligand binding...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28107521/differential-roles-of-axin1-and-axin2-in-tankyrase-inhibitor-induced-formation-of-degradasomes-and-%C3%AE-catenin-degradation
#2
Tor Espen Thorvaldsen, Nina Marie Pedersen, Eva Maria Wenzel, Harald Stenmark
Inhibition of the tankyrase enzymes (TNKS1 and TNKS2) has recently been shown to induce highly dynamic assemblies of β-catenin destruction complex components known as degradasomes, which promote degradation of β-catenin and reduced Wnt signaling activity in colorectal cancer cells. AXIN1 and AXIN2/Conductin, the rate-limiting factors for the stability and function of endogenous destruction complexes, are stabilized upon TNKS inhibition due to abrogated degradation of AXIN by the proteasome. Since the role of AXIN1 versus AXIN2 as scaffolding proteins in the Wnt signaling pathway still remains incompletely understood, we sought to elucidate their relative contribution in the formation of degradasomes, as these protein assemblies most likely represent the morphological and functional correlates of endogenous β-catenin destruction complexes...
2017: PloS One
https://www.readbyqxmd.com/read/28107381/in-vivo-two-photon-imaging-of-astrocytes-in-gfap-gfp-transgenic-mice
#3
Dongjun Guo, Jia Zou, Nicholas Rensing, Michael Wong
Astrocytes play important roles in normal brain function and neurological diseases. In vivo two-photon excitation laser scanning microscopy has the potential to reveal rapid, dynamic structural changes in cells in a variety of physiological and pathological conditions. The type of in vivo imaging method has been shown to affect the plasticity of dendritic spines of neurons, but the optimal in vivo imaging methods of astrocytes have not been established. We compared open-skull and thinned-skull imaging methods for two-photon laser microscopy of live astrocytes in neocortex of GFAP-GFP transgenic mice...
2017: PloS One
https://www.readbyqxmd.com/read/28107207/dynamic-mechanical-interactions-between-neighboring-airspaces-determine-cyclic-opening-and-closure-in-injured-lung
#4
Ludovic Broche, Gaetano Perchiazzi, Liisa Porra, Angela Tannoia, Mariangela Pellegrini, Savino Derosa, Alessandra Sindaco, João Batista Borges, Loïc Degrugilliers, Anders Larsson, Göran Hedenstierna, Anthony S Wexler, Alberto Bravin, Sylvia Verbanck, Bradford J Smith, Jason H T Bates, Sam Bayat
OBJECTIVES: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. DESIGN: Experimental animal study...
January 19, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28107094/dynamic-volume-assessment-of-hepatocellular-carcinoma-in-rat-livers-using-a-clinical-3t-mri-and-novel-segmentation
#5
Lorenzo A Orci, Graziano Oldani, Stephanie Lacotte, Florence Slits, Iris Friedli, Wolfgang Wirth, Christian Toso, Jean-Paul Vallée, Lindsey A Crowe
PURPOSE: In vivo liver cancer research commonly uses rodent models. One of the limitations of such models is the lack of accurate and reproducible endpoints for a dynamic assessment of growing tumor nodules. The aim of this study was to validate a noninvasive, true volume segmentation method using two rat hepatocellular carcinoma (HCC) models, correlating magnetic resonance imaging (MRI) with histological volume measurement, and with blood levels of α-fetoprotein. MATERIALS AND METHODS: We used 3T clinical MRI to quantify tumor volume with follow-up over time...
January 20, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28107009/nmr-and-computation-reveal-a-pressure-sensitive-folded-conformation-of-trp-cage
#6
Soichiro Kitazawa, Martin J Fossat, Scott A McCallum, Angel E Garcia, Catherine Ann Royer
Beyond defining the structure and stability of folded states of proteins, primary amino acid sequences determine all of the features of their conformational landscapes. Characterizing how sequence modulates the population of protein excited states or folding pathways requires atomic level detailed structural and energetic information. Such insight is essential for improving protein design strategies, as well as for interpreting protein evolution. Here, high pressure NMR and molecular dynamics simulations were combined to probe the conformational landscape of a small model protein, the tryptophan cage variant, Tc5b...
January 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28106614/study-of-intrapatient-variability-and-reproducibility-of-quantitative-tumor-perfusion-parameters-evaluated-with-dynamic-contrast-enhanced-ultrasonography
#7
Nathalie Lassau, Bénédicte Coiffier, Laura Faivre, Baya Benatsou, Sophie Bidault, Elizabeth Girard, Bernard Asselain, Stéphanie Pitre-Champagnat, Serge Koscielny
OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation...
January 18, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28106194/connectivity-pattern-modifies-excited-state-relaxation-dynamics-of-fluorophore-photoswitch-molecular-dyads
#8
F Schweighöfer, J Moreno, S Bobone, S Chiantia, A Herrmann, S Hecht, J Wachtveitl
In order to modulate the emission of BODIPY fluorophores, they were connected to a diarylethene (DAE) photoswitch via phenylene-ethynylene linkers of different lengths and orientations. The latter allowed for modulation of the electronic coupling in the prepared four BODIPY-DAE dyads, which were compared also to appropriate BODIPY and DAE model compounds by steady state as well as time-resolved spectroscopies. In their open isomers, all dyads show comparable luminescence behavior indicative of an unperturbed BODIPY fluorophore...
January 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28106109/center-of-mass-in-complex-networks
#9
Chuanji Fu, Yachun Gao, Shimin Cai, Hongchun Yang, Chun Yang
Network dynamics is always a big challenge in nonlinear dynamics. Although great advancements have been made in various types of complex systems, an universal theoretical framework is required. In this paper, we introduce the concept of center of 'mass' of complex networks, where 'mass' stands for node importance or centrality in contrast to that of particle systems, and further prove that the phase transition and evolutionary state of the system can be characterized by the activity of center of 'mass'. The steady states of several complex networks (gene regulatory networks and epidemic spreading systems) are then studied by analytically calculating the decoupled equation of the dynamic activity of center of 'mass', which is derived from the dynamic equation of the complex networks...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104812/antibody-secreting-plasma-cells-persist-for-decades-in-human-intestine
#10
Ole J B Landsverk, Omri Snir, Raquel Bartolomé Casado, Lisa Richter, Jeff E Mold, Pedro Réu, Rune Horneland, Vemund Paulsen, Sheraz Yaqub, Einar Martin Aandahl, Ole M Øyen, Hildur Sif Thorarensen, Mehran Salehpour, Göran Possnert, Jonas Frisén, Ludvig M Sollid, Espen S Baekkevold, Frode L Jahnsen
Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively...
January 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28104801/aquatic-insects-in-a-multistress-environment-cross-tolerance-to-salinity-and-desiccation
#11
Susana Pallarés, María Botella-Cruz, Paula Arribas, Andrés Millán, Josefa Velasco
Exposing organims to a particular stressor may enhance tolerance to a subsequent stress, when protective mechanisms against both stressors are shared. Such cross-tolerance is a common adaptive response in dynamic multivariate environments and often indicates potential co-evolution of stress traits. Many aquatic insects in inland saline waters from Mediterranean-climate regions are sequentially challenged with salinity and desiccation stress. Thus, cross-tolerance to these physiologically similar stressors could have been positively selected in insects of these regions...
January 19, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28104696/systematic-characterization-of-human-testis-specific-actin-capping-protein-%C3%AE-3-as-a-possible-biomarker-for-male-infertility
#12
T Soda, Y Miyagawa, N Ueda, K Takezawa, H Okuda, S Fukuhara, K Fujita, H Kiuchi, M Uemura, Y Okamoto, A Tsujimura, H Tanaka, N Nonomura
STUDY QUESTION: Is actin capping protein (CP) β3 involved in human spermatogenesis and male infertility? SUMMARY ANSWER: Human CPβ3 (hCPβ3) is expressed in testis, changes its localization dynamically during spermatogenesis, and has some association with male infertility. WHAT IS KNOWN ALREADY: The testis-specific α subunit of CP (CPα3) was previously identified in human, and mutations in the cpα3 gene in mouse were shown to induce malformation of the sperm head and male infertility...
January 18, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28104642/evaluation-of-encephaloduroarteriosynangiosis-efficacy-using-probabilistic-independent-component-analysis-applied-to-dynamic-susceptibility-contrast-perfusion-mri
#13
A N Laiwalla, F Kurth, K Leu, R Liou, J Pamplona, Y C Ooi, N Salamon, B M Ellingson, N R Gonzalez
BACKGROUND AND PURPOSE: Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion...
January 19, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28102959/x-ray-scatter-correction-for-multi-source-interior-computed-tomography
#14
Hao Gong, Hao Yan, Xun Jia, Bin Li, Ge Wang, Guohua Cao
PURPOSE: The schemes of multi-source interior computed tomography (CT) have shown promise for ultra-fast, organ-oriented, and low-dose dynamic imaging. Besides forward scattering, x-ray cross scattering from multiple x-ray sources activated simultaneously can further degrade image quality. Here, we investigate the overall x-ray scattering artifact in a recently proposed multi-source interior CT architecture, and present two methods for scatter correction. METHODS: Compared to single-source global CT, scattering in multi-source interior CT architecture is affected by two new factors: cross scattering from simultaneously activated multiple x-ray sources and region-of-interest (ROI) oriented interior CT mode...
January 2017: Medical Physics
https://www.readbyqxmd.com/read/28102833/a-multimodal-approach-to-estimating-vigilance-using-eeg-and-forehead-eog
#15
Wei-Long Zheng, Baoliang Lu
OBJECTIVE: Covert aspects of ongoing user mental states provide key context information for user-aware human computer interactions. In this paper, we focus on the problem of estimating the vigilance of users using EEG and EOG signals. APPROACH: The PERCLOS index as vigilance annotation is obtained from eye tracking glasses. To improve the feasibility and wearability of vigilance estimation devices for real-world applications, we adopt a novel electrode placement for forehead EOG and extract various eye movement features, which contain the principal information of traditional EOG...
January 19, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28102310/coordinated-cell-motility-is-regulated-by-a-combination-of-lkb1-farnesylation-and-kinase-activity
#16
S Wilkinson, Y Hou, J T Zoine, J Saltz, C Zhang, Z Chen, L A D Cooper, A I Marcus
Cell motility requires the precise coordination of cell polarization, lamellipodia formation, adhesion, and force generation. LKB1 is a multi-functional serine/threonine kinase that associates with actin at the cellular leading edge of motile cells and suppresses FAK. We sought to understand how LKB1 coordinates these multiple events by systematically dissecting LKB1 protein domain function in combination with live cell imaging and computational approaches. We show that LKB1-actin colocalization is dependent upon LKB1 farnesylation leading to RhoA-ROCK-mediated stress fiber formation, but membrane dynamics is reliant on LKB1 kinase activity...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102029/biochemical-markers-to-predict-internal-browning-disorders-in-rocha-pear-during-storage-under-high-co2
#17
Teresa Deuchande, Christian Larrigaudière, Umbelina Guterres, Susana M P Carvalho, Marta W Vasconcelos
BACKGROUND: The aim of this study was to identify biochemical markers to predict internal browning disorders (IBD) in 'Rocha' pear. Fruit from five orchards were stored for 45 days under cold air followed by 100 days in browning inducing controlled atmosphere (CA) conditions (1 kPa O2 + 10 kPa CO2 ). RESULTS: Relationships between concentrations of ethanol (EtOH), acetaldehyde (AcDH), ascorbic acid (AA) and the activities of peroxidase (POX) and polyphenoloxidase (PPO) and IBD incidence were established...
January 19, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28100829/a-mathematical-model-of-tumour-angiogenesis-growth-regression-and-regrowth
#18
Guillermo Vilanova, Ignasi Colominas, Hector Gomez
Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs). They may undergo alternating stages of growth, regression and regrowth. Following a phase-field methodology, we propose a model of tumour angiogenesis that reproduces the aforementioned features and highlights the importance of vascular regression and regrowth...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28100654/dissociation-between-sustained-single-neuron-spiking-%C3%AE-rhythmicity-and-transient-%C3%AE-lfp-oscillations-in-primate-motor-cortex
#19
Michael Everett Rule, Carlos E Vargas-Irwin, John P Donoghue, Wilson Truccolo
Determining the relationship between single-neuron spiking and transient (~20 Hz) beta local field potential (β-LFP) oscillations is an important step for understanding the role of these oscillations in motor cortex. We show that while motor cortex firing rates and beta spiking rhythmicity remain sustained during steady-state movement preparation periods, β-LFP oscillations emerge, in contrast, as short transient events. Single-neuron mean firing rates within and outside transient β-LFP events showed no differences, and no consistent correlation was found between the beta oscillations' amplitude and firing rates, as was the case for movement and visual-cue related β-LFP suppression...
January 18, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28100610/the-measles-virus-receptor-slamf1-can-mediate-particle-endocytosis
#20
Daniel Gonçalves-Carneiro, Jane A McKeating, Dalan Bailey
: The signalling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for Measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to co-localise with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells...
January 18, 2017: Journal of Virology
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