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https://www.readbyqxmd.com/read/29169118/characterization-of-a-microbial-polysaccharide-based-bioflocculant-and-its-anti-inflammatory-and-pro-coagulant-activity
#1
Chunying Zhong, Gang Cao, Kuan Rong, Zhengwu Xia, Ting Peng, Honggao Chen, Jiangang Zhou
We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical characteristics of MBF-15 were determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for its biocompatibility by examining its inflammatory, coagulant, and hemostatic properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible nitric oxide synthase, production of nitric oxide, and secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6...
November 16, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29168523/electroconductive-nanoscale-topography-for-enhanced-neuronal-differentiation-and-electrophysiological-maturation-of-human-neural-stem-cells
#2
Kisuk Yang, Seung Jung Yu, Jong Seung Lee, Hak-Rae Lee, Gyeong-Eon Chang, Jungmok Seo, Taeyoon Lee, Eunji Cheong, Sung Gap Im, Seung-Woo Cho
Biophysical cues, such as topography, and electrical cues can provide external stimulation for the promotion of stem cell neurogenesis. Here, we demonstrate an electroconductive surface nanotopography for enhancing neuronal differentiation and the functional maturation of human neural stem cells (hNSCs). The electroconductive nanopatterned substrates were prepared by depositing a thin layer of titanium (Ti) with nanograting topographies (150 to 300 nm groove/ridge, the thickness of the groove - 150 μm) onto polymer surfaces...
November 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/29168260/prosystemin-a-prohormone-that-modulates-plant-defense-barriers-is-an-intrinsically-disordered-protein
#3
Martina Buonanno, Mariangela Coppola, Ilaria Di Lelio, Donata Molisso, Marilisa Leone, Francesco Pennacchio, Emma Langella, Rosa Rao, Simona Maria Monti
Prosystemin, originally isolated from Lycopersicon esculentum, is a tomato pro-hormone of 200 aminoacid residues which releases a bioactive peptide of 18 aminoacids called Systemin. This signaling peptide is involved in the activation of defense genes in solanaceous plants in response to herbivore feeding damage. Using biochemical, biophysical and bioinformatics approaches we characterized Prosystemin, showing that it is an intrinsically disordered protein possessing a few secondary structure elements within the sequence...
November 23, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29167428/low-ph-induced-conformational-change-and-dimerization-of-sortilin-triggers-endocytosed-ligand-release
#4
Nadia Leloup, Philip Lössl, Dimphna H Meijer, Martha Brennich, Albert J R Heck, Dominique M E Thies-Weesie, Bert J C Janssen
Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167333/authentic-patient-derived-hepatitis-c-virus-infects-and-productively-replicates-in-primary-cd4-and-cd8-t-lymphocytes-in-vitro
#5
Georgia Skardasi, Annie Y Chen, Tomasz I Michalak
Accumulated evidence indicates that immune cells can support replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembled. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed properties of virus produced by these cells...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29166018/discovery-of-small-molecule-inhibitors-of-ubiquitin-specific-protease-7-usp7-using-integrated-nmr-and-in-silico-techniques
#6
Paola Di Lello, Richard Pastor, Jeremy M Murray, Robert A Blake, Frederick Cohen, Terry D Crawford, Joy Drobnick, Jason Drummond, Lorna Kategaya, Tracy Kleinheinz, Till Maurer, Lionel Rouge, Xianrui Zhao, Ingrid Wertz, Chudi Ndubaku, Vickie Tsui
USP7 is a deubiquitinase implicated in destabilizing the tumor suppressor p53 and for this reason it has gained increasing attention as a potential oncology target for small molecule inhibitors. Herein we describe the biophysical, biochemical and computational approaches that led to the identification of 4-(2-aminopyridin-3-yl)-phenol compounds described by Kategaya et al.1 as specific inhibitors of USP7. Fragment based lead discovery (FBLD) by NMR combined with virtual screening and re-mining of biochemical high-throughput screening (HTS) hits led to the discovery of a series of ligands that bind in the "palm" region of the catalytic domain of USP7 and inhibit its catalytic activity...
November 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29164289/cell-membrane-biophysics-with-optical-tweezers
#7
H Moysés Nussenzveig
Membrane elastic properties play important roles in regulating cell shape, motility, division and differentiation. Here I review optical tweezer (OT) investigations of membrane surface tension and bending modulus, emphasizing didactic aspects and insights provided for cell biology. OT measurements employ membrane-attached microspheres to extract long cylindrical nanotubes named tethers. The Helfrich-Canham theory yields elastic parameters in terms of tether radius and equilibrium extraction force. It assumes initial point-like microsphere attachment and no cytoskeleton content within tethers...
November 21, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/29164072/a-new-strain-collection-for-improved-expression-of-outer-membrane-proteins
#8
Ina Meuskens, Marcin Michalik, Nandini Chauhan, Dirk Linke, Jack C Leo
Almost all integral membrane proteins found in the outer membranes of Gram-negative bacteria belong to the transmembrane β-barrel family. These proteins are not only important for nutrient uptake and homeostasis, but are also involved in such processes as adhesion, protein secretion, biofilm formation, and virulence. As surface exposed molecules, outer membrane β-barrel proteins are also potential drug and vaccine targets. High production levels of heterologously expressed proteins are desirable for biochemical and especially structural studies, but over-expression and subsequent purification of membrane proteins, including outer membrane proteins, can be challenging...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29163925/quantitative-first-principles-calculations-of-protein-circular-dichroism-in-the-near-ultraviolet
#9
Zhuo Li, Jonathan D Hirst
Vibrational structure in the near-UV circular dichroism (CD) spectra of proteins is an important source of information on protein conformation and can be exploited to study structure and folding. A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper interpretation of and insight into biophysical and simulation studies of protein dynamics and folding. We have developed new models of the aromatic side chain chromophores toluene, p-cresol and 3-methylindole, which incorporate ab initio calculations of the Franck-Condon effect into first principles calculations of CD using an exciton approach...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29162865/gaba-a-receptor-coupling-junction-and-pore-gabrb3-mutations-are-linked-to-early-onset-epileptic-encephalopathy
#10
Ciria C Hernandez, Yujia Zhang, Ningning Hu, Dingding Shen, Wangzhen Shen, Xiaoyan Liu, Weijing Kong, Yuwu Jiang, Robert L Macdonald
GABAA receptors are brain inhibitory chloride ion channels. Here we show functional analyses and structural simulations for three de novo missense mutations in the GABAA receptor β3 subunit gene (GABRB3) identified in patients with early-onset epileptic encephalopathy (EOEE) and profound developmental delay. We sought to obtain insights into the molecular mechanisms that might link defects in GABAA receptor biophysics and biogenesis to patients with EOEE. The mutant residues are part of conserved structural domains such as the Cys-loop (L170R) and M2-M3 loop (A305V) that form the GABA binding/channel gating coupling junction and the channel pore (T288N), which are functionally coupled during receptor activation...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162692/phosphorylation-of-huntingtin-at-residue-t3-is-decreased-in-huntington-s-disease-and-modulates-mutant-huntingtin-protein-conformation
#11
Cristina Cariulo, Lucia Azzollini, Margherita Verani, Paola Martufi, Roberto Boggio, Anass Chiki, Sean M Deguire, Marta Cherubini, Silvia Gines, J Lawrence Marsh, Paola Conforti, Elena Cattaneo, Iolanda Santimone, Ferdinando Squitieri, Hilal A Lashuel, Lara Petricca, Andrea Caricasole
Posttranslational modifications can have profound effects on the biological and biophysical properties of proteins associated with misfolding and aggregation. However, their detection and quantification in clinical samples and an understanding of the mechanisms underlying the pathological properties of misfolding- and aggregation-prone proteins remain a challenge for diagnostics and therapeutics development. We have applied an ultrasensitive immunoassay platform to develop and validate a quantitative assay for detecting a posttranslational modification (phosphorylation at residue T3) of a protein associated with polyglutamine repeat expansion, namely Huntingtin, and characterized its presence in a variety of preclinical and clinical samples...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29162464/biochemical-and-biophysical-characterization-of-curcumin-binding-to-human-mitotic-kinesin-eg5-iinsights-into-the-inhibitory-mechanism-of-curcumin-on-eg5
#12
Darpan Raghav, Jomon Sebastian, Krishnan Rathinasamy
In this study we have characterized the biochemical and biophysical interactions of curcumin with the mitotic kinesin Eg5 which plays a pivotal role in the separation of centrosomes during cell division. Curcumin bound to the purified Eg5 (Eg5-437H) with a Kd value of 7.8mM. The temperature dependent binding analysis and evaluation of thermodynamic parameters indicated the involvement of static quenching mechanism in the binding process. Evidences from competition experiment with monastrol indicated that curcumin bound to Eg5 at a novel druggable site...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29162462/functional-role-of-the-conserved-glycine-residues-gly481-and-gly482-of-the-%C3%AE-glutamyltranspeptidase-from-bacillus-licheniformis
#13
Meng-Chun Chi, Ming-Guan Lin, Yu-Yi Chen, Long-Liu Lin, Tzu-Fan Wang
Six mutants bearing single amino acid substitutions in the small subunit of Bacillus licheniformis γ-glutamyltranspeptudase (BlGGT) have been constructed by site-directed mutagenesis. The resultant enzymes were overexpressed in Escherichia coli and purified by affinity chromatography for biochemical and biophysical characterizations. Replacing Gly481 by either Ala or Glu did affect both autocatalytic processing and catalytic activity of the enzyme, but the substitution of this residue to arginine resulted in an unprocessed enzyme with insignificant catalytic activity...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29162368/role-of-hydroxyl-groups-in-the-b-ring-of-flavonoids-in-stabilization-of-the-hoogsteen-paired-third-strand-of-poly-u-poly-a-poly-u-triplex
#14
Ankur Bikash Pradhan, Sutanwi Bhuiya, Lucy Haque, Suman Das
We have reported the interaction of two flavonoids namely quercetin (Q) and morin (M) with double stranded poly(A).poly(U) (herein after A.U) and triple stranded poly(U).poly(A)*poly(U) (herein after U.A*U, dot represents the Watson-Crick and asterisk represents Hoogsteen base pairing respectively) in this article. It has been observed that relative positions of hydroxyl groups on the B-ring of the flavonoids affect the stabilization of RNA. The double strand as well as the triple strand of RNA-polymers become more stabilized in presence of Q, however both the duplex and triplex remain unaffected in presence of M...
November 18, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29162005/on-rhythms-in-neuronal-networks-with-recurrent-excitation
#15
Christoph Börgers, R Melody Takeuchi, Daniel T Rosebrock
We investigate rhythms in networks of neurons with recurrent excitation, that is, with excitatory cells exciting each other. Recurrent excitation can sustain activity even when the cells in the network are driven below threshold, too weak to fire on their own. This sort of "reverberating" activity is often thought to be the basis of working memory. Recurrent excitation can also lead to "runaway" transitions, sudden transitions to high-frequency firing; this may be related to epileptic seizures. Not all fundamental questions about these phenomena have been answered with clarity in the literature...
November 21, 2017: Neural Computation
https://www.readbyqxmd.com/read/29161764/mechanism-of-doxorubicin-cardiotoxicity-evaluated-by-integrating-multiple-molecular-effects-into-a-biophysical-model
#16
M Fernandez-Chas, M J Curtis, S A Niederer
BACKGROUND AND PURPOSE: Doxorubicin (DOX) is an effective cancer therapeutic agent but causes therapy-limiting cardiotoxicity. The effects of DOX and its metabolite doxorubicinol (DOXL) on individual channels have been well characterised in isolation. However, it is unknown how the action and interaction of affected channels combine to generate the phenotypic cardiotoxic outcome. We sought to develop an in silico model that links drug effects on channels to action potential duration (APD) and intracellular Ca(2+) concentration in order to address this gap in knowledge...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29161510/solvation-structure-and-thermodynamic-mapping-sstmap-an-open-source-flexible-package-for-the-analysis-of-water-in-molecular-dynamics-trajectories
#17
Kamran Haider, Anthony Cruz, Steven Ramsey, Michael K Gilson, Thomas Kurtzman
We have developed SSTMap, a software package for mapping structural and thermodynamic water properties in molecular dynamics trajectories. The package introduces automated analysis and mapping of local measures of frustration and enhancement of water structure. The thermodynamic calculations are based on Inhomogeneous Fluid Solvation Theory (IST), which is implemented using both site-based and grid-based approaches. The package also extends the applicability of solvation analysis calculations to multiple molecular dynamics (MD) simulation programs by using existing cross-platform tools for parsing MD parameter and trajectory files...
November 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29161483/-spatio-temporal-analysis-of-the-biophysical-and-ecological-conditions-of-triatoma-dimidiata-hemiptera-reduviidae-triatominae-in-the-northeast-region-of-colombia
#18
Jaime Badel-Mogollón, Laura Rodríguez-Figueroa, Gabriel Parra-Henao
INTRODUCTION: Due to the lack of information regarding biophysical and spatio-temporal conditions (hydrometheorologic and vegetal coverage density) in areas with Triatoma dimidiata in the Colombian departments of Santander and Boyacá, there is a need to elucidate the association patterns of these variables to determine the distribution and control of this species. OBJECTIVE: To make a spatio-temporal analysis of biophysical variables related to the distribution of T...
March 29, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/29161365/genome-scale-analysis-ofescherichia-coliwith-a-comprehensive-prokaryotic-sequence-based-biophysical-model-of-translation-initiation-and-elongation
#19
Gilad Shaham, Tamir Tuller
Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation...
November 17, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29161079/a-new-frontier-in-immunometabolism-cholesterol-in-lung-health-and-disease
#20
Michael B Fessler
The lung has a unique relationship to cholesterol that is shaped by its singular physiology. On the one hand, the lungs receive the full cardiac output and have a predominant dependence on plasma lipoprotein uptake for their cholesterol supply. On the other hand, surfactant lipids, including cholesterol, are continually susceptible to oxidation owing to direct environmental exposure and must be cleared or recycled because of the very narrow biophysical mandates placed upon surfactant lipid composition. Interestingly, increased lipid-laden macrophage "foam cells" have been noted in a wide range of human lung pathologies...
November 2017: Annals of the American Thoracic Society
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