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Biophysic

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https://www.readbyqxmd.com/read/28098556/genetic-defects-in-%C3%AE-spectrin-and-tau-sensitize-c-elegans-axons-to-movement-induced-damage-via-torque-tension-coupling
#1
Michael Krieg, Jan Stühmer, Juan G Cueva, Richard Fetter, Kerri A Spliker, Daniel Cremers, Kang Shen, Alexander R Dunn, Miriam B Goodman
Our bodies are in constant motion and so are the neurons that invade each tissue. Motion-induced neuron deformation and damage are associated with several neurodegenerative conditions. Here, we investigated the question of how the neuronal cytoskeleton protects axons and dendrites from mechanical stress, exploiting mutations in UNC-70 β-spectrin, PTL-1 tau/MAP2-like and MEC-7 β-tubulin proteins in Caenorhabditis elegans. We found that mechanical stress induces supercoils and plectonemes in the sensory axons of spectrin and tau double mutants...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098306/effective-viscosity-and-dynamics-of-spreading-epithelia-a-solvable-model
#2
C Blanch-Mercader, R Vincent, E Bazellières, X Serra-Picamal, X Trepat, J Casademunt
Collective cell migration in spreading epithelia in controlled environments has become a landmark in our current understanding of fundamental biophysical processes in development, regeneration, wound healing or cancer. Epithelial monolayers are treated as thin layers of a viscous fluid that exert active traction forces on the substrate. The model is exactly solvable and shows a broad range of applicabilities for the quantitative analysis and interpretation of force microscopy data of monolayers from a variety of experiments and cell lines...
January 18, 2017: Soft Matter
https://www.readbyqxmd.com/read/28098278/understanding-the-connection-between-conformational-changes-of-peptides-and-equilibrium-thermal-fluctuations
#3
Miguel A Soler, José Zúñiga, Alberto Requena, Adolfo Bastida
Despite the increasing evidence that conformational transitions in peptides and proteins are driven by specific vibrational energy pathways along the molecule, the current experimental techniques of analysis do as yet not allow to study these biophysical processes in terms of anisotropic energy flows. Computational methods offer a complementary approach to obtain a more detailed understanding of the vibrational and conformational dynamics of these systems. Accordingly, in this work we investigate jointly the vibrational energy distribution and the conformational dynamics of trialanine peptide in water solution at room temperature by applying the Instantaneous Normal Mode analysis to the results derived from equilibrium molecular dynamics simulations...
January 18, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28097603/comprehensive-preclinical-evaluation-of-a-multi-physics-model-of-liver-tumor-radiofrequency-ablation
#4
Chloé Audigier, Tommaso Mansi, Hervé Delingette, Saikiran Rapaka, Tiziano Passerini, Viorel Mihalef, Marie-Pierre Jolly, Raoul Pop, Michele Diana, Luc Soler, Ali Kamen, Dorin Comaniciu, Nicholas Ayache
PURPOSE: We aim at developing a framework for the validation of a subject-specific multi-physics model of liver tumor radiofrequency ablation (RFA). METHODS: The RFA computation becomes subject specific after several levels of personalization: geometrical and biophysical (hemodynamics, heat transfer and an extended cellular necrosis model). We present a comprehensive experimental setup combining multimodal, pre- and postoperative anatomical and functional images, as well as the interventional monitoring of intra-operative signals: the temperature and delivered power...
January 17, 2017: International Journal of Computer Assisted Radiology and Surgery
https://www.readbyqxmd.com/read/28096333/biophysical-properties-of-the-clinical-stage-antibody-landscape
#5
Tushar Jain, Tingwan Sun, Stéphanie Durand, Amy Hall, Nga Rewa Houston, Juergen H Nett, Beth Sharkey, Beata Bobrowicz, Isabelle Caffry, Yao Yu, Yuan Cao, Heather Lynaugh, Michael Brown, Hemanta Baruah, Laura T Gray, Eric M Krauland, Yingda Xu, Maximiliano Vásquez, K Dane Wittrup
Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however, achieving drug-like properties at the same time is an additional requirement that is receiving increased attention. In this work, we attempt to quantify the historical limits of acceptability for multiple biophysical metrics of "developability...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096331/one-step-design-of-a-stable-variant-of-the-malaria-invasion-protein-rh5-for-use-as-a-vaccine-immunogen
#6
Ivan Campeotto, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M Marshall, Sarah E Silk, Katherine E Wright, Simon J Draper, Matthew K Higgins, Sarel J Fleishman
Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094993/the-biophysics-of-artificially-expanded-genetic-information-systems-thermodynamics-of-dna-duplexes-containing-matches-and-mismatches-involving-2-amino-3-nitropyridin-6-one-z-and-imidazo-1-2-a-1-3-5-triazin-4-8h-one-p
#7
Xiaoyu Wang, Shuichi Hoshika, Raymond J Peterson, Myong-Jung Kim, Steven A Benner, Jason D Kahn
Synthetic nucleobases presenting non-Watson Crick arrangements of hydrogen bond donor and acceptor groups can form additional nucleotide pairs that stabilize duplex DNA independent of the standard A:T and G:C pairs. The pair between 2-amino-3-nitropyridin-6-one 2'-deoxyriboside (presenting a {donor-donor-acceptor} hydrogen bonding pattern on the Watson-Crick face of the small component, trivially designated Z) and imidazo[1,2-a]-1,3,5-triazin-4(8H)one 2'-deoxyriboside (presenting an {acceptor-acceptor-donor} hydrogen bonding pattern on the large component, trivially designated P) is one of these extra pairs for which a substantial amount of molecular biology has been developed...
January 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28094925/retinal-based-proton-pumping-in-the-near-infra-red
#8
Srividya Ganapathy, Hanka Venselaar, Que Chen, Huub J M de Groot, Klaas J Hellingwerf, Willem J de Grip
Proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) are retinal-based light-driven proton pumps which absorb visible light (maxima 520-540 nm). Shifting the action spectra of these proton pumps beyond 700 nm would generate new prospects in optogenetics, membrane sensor technology, and complementation of oxygenic phototrophy. We thereby investigated the effect of red-shifting analogs of retinal, combined with red-shifting mutations, on the spectral properties and pump activity of the resulting pigments. We investigated a variety of analogs, including many novel ones...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094776/new-insights-into-cooperative-binding-of-homeodomain-transcription-factors-prep1-and-pbx1-to-dna
#9
Chiara Zucchelli, Elena Ferrari, Francesco Blasi, Giovanna Musco, Chiara Bruckmann
PREP1 and PBX1 are homeodomain (HD) transcription factors that play crucial roles in embryonic development. Here, we present the first biophysical characterization of a PREP1 HD, and the NMR spectroscopic study of its DNA binding pocket. The data show that residues flanking the HD participate in DNA binding. The kinetic parameters for DNA binding of individual PREP1 and PBX1 HDs, and of their combination, show that isolated PREP1 and PBX1 HDs bind to DNA in a cooperative manner. A novel PREP1 motif, flanking the HD at the C-terminus, is required for cooperativity...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094527/binding-and-inhibitory-effect-of-dyes-amaranth-and-tartrazine-on-amyloid-fibrillation-in-lysozyme
#10
Anirban Basu, Gopinatha Suresh Kumar
Interaction of two food colorant dyes, amaranth and tartrazine, with lysozyme was studied employing multiple biophysical techniques. The dyes exhibited hypochromic changes in the presence of lysozyme. The intrinsic fluorescence of lysozyme was quenched by both dyes; amaranth was a more efficient quencher than tartrazine. The equilibrium constant of amaranth was higher than that of tartarzine. From FRET analysis, the binding distances for amaranth and tartrazine were calculated to be 4.51 and 3.93 nms, respectively...
January 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28093869/biosynthesis-of-micro-and-nanocrystals-of-pb-ii-hg-ii-and-cd-ii-sulfides-in-four-candida-species-a-comparative-study-of-in%C3%A2-vivo-and-in%C3%A2-vitro-approaches
#11
Mayra Cuéllar-Cruz, Daniela Lucio-Hernández, Isabel Martínez-Ángeles, Nicola Demitri, Maurizio Polentarutti, María J Rosales-Hoz, Abel Moreno
Nature produces biominerals (biogenic minerals) that are synthesized as complex structures, in terms of their physicochemical properties. These biominerals are composed of minerals and biological macromolecules. They are produced by living organisms and are usually formed through a combination of chemical, biochemical and biophysical processes. Microorganisms like Candida in the presence of heavy metals can biomineralize those metals to form microcrystals (MCs) and nanocrystals (NCs). In this work, MCs and NCs of PbS, HgS or HgCl2 as well as CdS are synthesized both in vitro (gels) and in vivo by four Candida species...
January 16, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28092950/two-phase-contiguous-supported-lipid-bilayer-model-for-membrane-rafts-via-polymer-blotting-and-stenciling
#12
Mark Jason Richards, Susan Daniel
The supported lipid bilayer has been portrayed as a useful model of the cell membrane compatible with many biophysical tools and techniques that demonstrate its appeal in learning about the basic features of the plasma membrane. However, some of its potential has yet to be realized, particularly in the area of bilayer patterning and phase/composition heterogeneity. In this work, we generate contiguous bilayer patterns as a model system that captures the general features of membrane domains and lipid rafts. Micropatterned polymer templates of two types are investigated for generating patterned bilayer formation: polymer blotting and polymer lift-off stenciling...
January 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28092942/advances-in-structural-and-single-molecule-methods-for-investigating-dna-lesion-bypass-and-repair-polymerases
#13
Austin T Raper, Andrew J Reed, Varun V Gadkari, Zucai Suo
Innovative advances in X-ray crystallography and single-molecule biophysics have yielded unprecedented insight into the mechanisms of DNA lesion bypass and damage repair. Time-dependent X-ray crystallography has been successfully applied to view the bypass of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), a major oxidative DNA lesion, and the incorporation of the triphosphate form, 8-oxo-dGTP, catalyzed by human DNA polymerase β. Significant findings of these studies are highlighted here, and their contributions to the current mechanistic understanding of mutagenic translesion DNA synthesis (TLS) and base excision repair are discussed...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092811/towards-the-structure-of-the-tir-domain-signalosome
#14
REVIEW
Surekha Nimma, Thomas Ve, Simon J Williams, Bostjan Kobe
TIR (Toll/interleukin-1 receptor/resistance protein) domains feature in animal, plant and bacterial proteins involved in innate immunity pathways and associated processes. They function through protein:protein interactions, in particular self-association and homotypic association with other TIR domains. Structures of TIR domains from all phyla have been determined, but common association modes have only emerged for plant and bacterial TIR domains, and not for mammalian TIR domains. Numerous attempts involving hybrid approaches, which have combined structural, computational, mutagenesis and biophysical data, have failed to converge onto common models of how these domains associate and function...
January 13, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28090431/a-role-for-3d-printing-in-kidney-on-a-chip-platforms
#15
Ryan D Sochol, Navin R Gupta, Joseph V Bonventre
The advancement of "kidney-on-a-chip" platforms - submillimeter-scale fluidic systems designed to recapitulate renal functions in vitro - directly impacts a wide range of biomedical fields, including drug screening, cell and tissue engineering, toxicity testing, and disease modelling. To fabricate kidney-on-a-chip technologies, researchers have primarily adapted traditional micromachining techniques that are rooted in the integrated circuit industry; hence the term, "chip." A significant challenge, however, is that such methods are inherently monolithic, which limits one's ability to accurately recreate the geometric and architectural complexity of the kidney in vivo...
March 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28089607/estimates-of-nasal-airflow-at-the-nasal-cycle-mid-point-improve-the-correlation-between-objective-and-subjective-measures-of-nasal-patency
#16
Courtney Gaberino, John S Rhee, Guilherme J M Garcia
INTRODUCTION: The nasal cycle represents a significant challenge when comparing pre- and post-surgery objective measures of nasal airflow. METHODS: Computational fluid dynamics (CFD) simulations of nasal airflow were conducted in 12 nasal airway obstruction patients showing significant nasal cycling between pre- and post-surgery computed tomography scans. To correct for the nasal cycle, mid-cycle models were created virtually. Subjective scores of nasal patency were obtained via the Nasal Obstruction Symptom Evaluation (NOSE) and unilateral visual analog scale (VAS)...
January 9, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28089451/crystallogenesis-of-membrane-proteins-mediated-by-polymer-bounded-lipid-nanodiscs
#17
Jana Broecker, Bryan T Eger, Oliver P Ernst
For some membrane proteins, detergent-mediated solubilization compromises protein stability and functionality, often impairing biophysical and structural analyses. Hence, membrane-protein structure determination is a continuing bottleneck in the field of protein crystallography. Here, as an alternative to approaches mediated by conventional detergents, we report the crystallogenesis of a recombinantly produced membrane protein that never left a lipid bilayer environment. We used styrene-maleic acid (SMA) copolymers to solubilize lipid-embedded proteins into SMA nanodiscs, purified these discs by affinity and size-exclusion chromatography, and transferred proteins into the lipidic cubic phase (LCP) for in meso crystallization...
January 3, 2017: Structure
https://www.readbyqxmd.com/read/28088651/limitations-in-biexponential-fitting-of-nmr-inversion-recovery-curves
#18
Mohammed Salman Shazeeb, Christopher H Sotak
NMR relaxation agents have long been employed as contrast agents in MRI. In many cases, the contrast agent is confined to either (i) the vascular and/or extracellular compartment (EC), as is the case with gadolinium(III)-based agents, or (ii) the intracellular compartment (IC), as is the case with manganese(II) ions. The compartmentalization of contrast agents often results in tissue-water (1)H relaxation profiles that are well modeled as biexponential. It has long been recognized that water exchange between compartments modifies the biexponential relaxation parameters (amplitudes and rate constants) from those that would be found in the absence of exchange...
January 6, 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/28088624/oxidative-phospholipidomics-in-health-and-disease-achievements-challenges-and-hopes
#19
REVIEW
Ana Reis
Phospholipid peroxidation products are recognized as important bioactive lipid mediators playing an active role as modulators in signalling events in inflammation, immunity and infection. The biochemical responses are determined by the oxidation structural features present in oxPL modulating biophysical and biological properties in model membranes and lipoproteins. In spite of the extensive work conducted with model systems over the last 20 years, the study of oxPL in biological systems has virtually stagnated...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088457/preformulation-characterization-stabilization-and-formulation-design-for-the-acrylodan-labeled-glucose-binding-protein-sm4-ac
#20
Neha Sahni, Rajoshi Chaudhuri, John M Hickey, Prakash Manikwar, Ajit D'Souza, Andrew Metters, Sangeeta B Joshi, C Russell Middaugh, David B Volkin
This study describes the physicochemical characterization, stabilization and formulation design of SM4-AC, an acrylodan labeled glucose/galactose binding protein for use in a continuous glucose monitoring device. The physical stability profile of SM4-AC as a function of pH and temperature was monitored using a combination of biophysical techniques and the resulting physical stability profile was visualized using an empirical phase diagram. Forced degradation chemical stability studies (Asn deamidation, Met oxidation) of SM4-AC were performed using a combination of capillary isoelectric focusing (cIEF), peptide mapping and reversed phase high performance liquid chromatography (RP-HPLC)...
January 11, 2017: Journal of Pharmaceutical Sciences
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