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https://www.readbyqxmd.com/read/29653090/vascular-and-molecular-pharmacology-of-the-metabolically-stable-cgrp-analogue-sax
#1
Majid Sheykhzade, Bahareh Abdolalizadeh, Cassandra Koole, Darryl Scott Pickering, Karin Dreisig, Sara Ellinor Johansson, Balsam Kadri Abboud, Rasmus Dreier, Jais Oliver Berg, Jørgen Lykke Jeppesen, Patrick M Sexton, Lars Edvinsson, Denise Wootten, Anette Sams
The main purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and a recently discovered metabolically stable CGRP analog, SAX, in isolated rat and human artery segments. In rat, CGRP and SAX induced similar vasodilatory responses in isolated mesenteric artery with the potency of SAX being lower than that of CGRP (vasodilatory pEC50 8.2 ± 0.12 and 9.0 ± 0.11, respectively). A corresponding difference in receptor binding affinity of SAX and CGRP was determined in rat cerebral membranes (pKi 8...
April 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29652417/nanoparticle-packing-within-block-copolymer-micelles-prepared-by-the-interfacial-instability-method
#2
Gauri M Nabar, Jessica O Winter, Barbara E Wyslouzil
The interfacial instability method has emerged as a viable approach for encapsulating high concentrations of nanoparticles (NPs) within morphologically diverse micelles. In this method, transient interfacial instabilities at the surface of an emulsion droplet guide self-assembly of block co-polymers and NP encapsulants. Although used by many groups, there are no systematic investigations exploring the relationship between NP properties and micelle morphology. Here, the effect of quantum dot (QD) and superparamagnetic iron oxide NP (SPION) concentration on the shape, size, and surface deformation of initially spherical poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles was examined...
April 13, 2018: Soft Matter
https://www.readbyqxmd.com/read/29649512/14-3-3-protein-directly-interacts-with-the-kinase-domain-of-calcium-calmodulin-dependent-protein-kinase-kinase-camkk2
#3
Katarina Psenakova, Olivia Petrvalska, Salome Kylarova, Domenico Lentini Santo, Dana Kalabova, Petr Herman, Veronika Obsilova, Tomas Obsil
BACKGROUND: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+ /calmodulin-dependent kinase (CaMK) family involved in adiposity regulation, glucose homeostasis and cancer. This upstream activator of CaMKI, CaMKIV and AMP-activated protein kinase is inhibited by phosphorylation, which also triggers an association with the scaffolding protein 14-3-3. However, the role of 14-3-3 in the regulation of CaMKK2 remains unknown. METHODS: The interaction between phosphorylated CaMKK2 and the 14-3-3γ protein, as well as the architecture of their complex, were studied using enzyme activity measurements, small-angle x-ray scattering (SAXS), time-resolved fluorescence spectroscopy and protein crystallography...
April 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29644370/electrospun-zro-2-nanofibers-precursor-controlled-mesopore-ordering-and-evolution-of-garland-like-nanocrystal-arrays
#4
Shreyasi Chattopadhyay, Sandip Bysakh, Jony Saha, Goutam De
We observed that the hydrolysis-condensation reaction of precursors makes a significant difference in constructing ordered mesopores in electrospun ZrO2 nanofibers. Transmission-SAXS studies confirm the generation of uniform clusters of size ∼1.44 nm in the ZrOCl2·8H2O (inorganic salt) derived sol due to its relatively slow hydrolysis-condensation process. These initial -Zr-O-Zr- clusters acted as building blocks to form uniform 3D ordered cubic (Pm3[combining macron]m) mesopores in the presence of Pluronic F127 surfactant...
April 12, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29642404/improved-optical-and-morphological-properties-of-vinyl-substituted-hybrid-silica-materials-incorporating-a-zn-metalloporphyrin
#5
Zoltán Dudás, Eugenia Fagadar-Cosma, Adél Len, Loránd Románszki, László Almásy, Beatrice Vlad-Oros, Daniela Dascălu, Andraž Krajnc, Manfred Kriechbaum, Andrei Kuncser
This work is focused on a novel class of hybrid materials exhibiting enhanced optical properties and high surface areas that combine the morphology offered by the vinyl substituted silica host, and the excellent absorption and emission properties of 5,10,15,20-tetrakis( N -methyl-4-pyridyl)porphyrin-Zn(II) tetrachloride as a water soluble guest molecule. In order to optimize the synthesis procedure and the performance of the immobilized porphyrin, silica precursor mixtures of different compositions were used...
April 6, 2018: Materials
https://www.readbyqxmd.com/read/29626538/cluspro-fmft-saxs-ultra-fast-filtering-using-small-angle-x-ray-scattering-data-in-protein-docking
#6
Mikhail Ignatov, Andrey Kazennov, Dima Kozakov
We have recently demonstrated that incorporation of SAXS-based filtering in our heavily used docking server ClusPro improves docking results. However, the filtering step is time consuming, since ≈105 conformations have to be sequentially processed. At the same time we have demonstrated the possibility of ultra-fast systematic energy evaluation for all rigid body orientations of two proteins, by sampling using Fast Manifold Fourier Transform (FMFT), if energies are represented as a combination of convolution-like expressions...
April 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29619199/linking-the-structures-free-volumes-and-properties-of-ionic-liquid-mixtures
#7
Nicholas J Brooks, Franca Castiglione, Cara M Doherty, Andrew Dolan, Anita J Hill, Patricia A Hunt, Richard P Matthews, Michele Mauri, Andrea Mele, Roberto Simonutti, Ignacio J Villar-Garcia, Cameron C Weber, Tom Welton
The formation of ionic liquid (IL) mixtures has been proposed as an approach to rationally fine-tune the physicochemical properties of ILs for a variety of applications. However, the effects of forming such mixtures on the resultant properties of the liquids are only beginning to be understood. Towards a more complete understanding of both the thermodynamics of mixing ILs and the effect of mixing these liquids on their structures and physicochemical properties, the spatial arrangement and free volume of IL mixtures containing the common [C4 C1 im]+ cation and different anions have been systematically explored using small angle X-ray scattering (SAXS), positron annihilation lifetime spectroscopy (PALS) and129 Xe NMR techniques...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29613966/acute-paraesophageal-hernia-laparoscopic-repair-with-adjunct-t-fastener-gastropexy-for-the-high-operative-risk-patient
#8
Gabriel Arevalo, Jordan Wilkerson, Jonathan Saxe
BACKGROUND: In the emergent setting, most paraesophageal hernia (PEH) repairs are done by laparotomy with adjunct gastropexy or gastrostomy tube (GT) placement. This adjunct to the repair can be performed expeditiously by a laparoscopic approach by utilizing T-fasteners. We present our case series of patients with PEHs and acute gastric volvulus that were managed with laparoscopy and how patient characteristics can influence the repair technique. METHODS: Patients with high operative risk who underwent laparoscopic hiatal hernia repair with adjunct T-fastener gastropexy in the emergent setting between July 2014 and July 2016 were included in this study...
April 2018: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
https://www.readbyqxmd.com/read/29611597/on-the-structural-stability-of-guanosine-based-supramolecular-hydrogels
#9
Federica Carducci, Juliana S Yoneda, Rosangela Itri, Paolo Mariani
Supramolecular hydrogels formed from the self-assembly of low molecular weight derivatives are very attractive systems, because of their potential applications in nano- and bio-technology. In this paper, the stable and transparent hydrogels observed in binary mixtures of guanosine derivatives (G), namely guanosine 5'-monophosphate (GMP) and guanosine (Gua), dissolved in water (at volume fractions larger than 0.95), were investigated by microscopy techniques and Small Angle X-ray Scattering (SAXS). The results confirm the presence of G-quadruplexes, chiral cylindrical rods obtained by the regular stacking of self-assembled planar cyclic guanosine quartets...
April 3, 2018: Soft Matter
https://www.readbyqxmd.com/read/29608608/solution-scattering-study-of-the-bacillus-subtilis-pgds-enzyme-involved-in-poly-%C3%AE-glutamic-acids-degradation
#10
Jumei Zeng, Yun Jin, Zhongchuan Liu
The PgdS enzyme is a poly-γ-glutamic (γ-PGA) hydrolase, which has potential application for a controllable degradation of γ-PGA by enzymatic depolymerization; however, the structure of PgdS is still unknown. Here, to study in detail the full-length PgdS structure, we analyze the low-resolution architecture of PgdS hydrolase from Bacillus subtilis in solution using small angle X-ray scattering (SAXS) method. Combining with other methods, like dynamic light scattering and mutagenesis analyses, a model for the full length structure and the possible substrate delivery route of PgdS are proposed...
2018: PloS One
https://www.readbyqxmd.com/read/29605933/modeling-structure-and-dynamics-of-protein-complexes-with-saxs-profiles
#11
Dina Schneidman-Duhovny, Michal Hammel
Small-angle X-ray scattering (SAXS) is an increasingly common and useful technique for structural characterization of molecules in solution. A SAXS experiment determines the scattering intensity of a molecule as a function of spatial frequency, termed SAXS profile. SAXS profiles can be utilized in a variety of molecular modeling applications, such as comparing solution and crystal structures, structural characterization of flexible proteins, assembly of multi-protein complexes, and modeling of missing regions in the high-resolution structure...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29604875/solvent-effect-on-fret-spectroscopic-ruler
#12
Songyuan Qu, Chuanbo Liu, Qiong Liu, Wei Wu, Baoji Du, Jin Wang
A discrepancy has emerged in recent years between single-molecule Förster resonance energy transfer (smFRET) measurements and small angle X-ray scattering (SAXS) or small angle neutron scattering experiments in the study of unfolded or intrinsically disordered proteins in denaturing solutions. Despite significant advances that have been made in identifying various factors which may have contributed to the manifestation of the so-called smFRET-SAXS discrepancy, no consensus has been reached so far on its original source or eventual resolution...
March 28, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29602907/an-n-terminally-truncated-form-of-cyclic-gmp-dependent-protein-kinase-i%C3%AE-pkg-i%C3%AE-is-monomeric-autoinhibited-and-provides-a-model-for-activation
#13
Thomas M Moon, Jessica L Sheehe, Praveena Nukareddy, Lydia W Nausch, Jessica Wohlfahrt, Dwight E Matthews, Donald K Blumenthal, Wolfgang R Dostmann
The type I cGMP-dependent protein kinases serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53)...
March 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29601962/improvement-in-lubricating-properties-of-tritonx-100-n-c-10-h-21-oh-h-2-o-lamellar-liquid-crystals-with-the-amphiphilic-ionic-liquid-1-alkyl-3-methylimidazolium-hexafluorophosphate
#14
Liping Chen, Jie Han, Lingling Ge, Lei Fan, Rong Guo
The applications of ionic liquids (ILs)/lamellar liquid crystals (LLCs) have great potential in nanotribology because they could be used where conventional oils could not work. To clarify the lubricating mechanism, herein, ILs/LLCs lubricants were prepared by addition of amphiphilic 1-alkyl-3-methylimidazolium hexafluorophosphate (Cn mimPF6 , n = 8, 12) into TritonX-100/n-C10 H21 OH/H2 O LLCs with different concentration. The influence of alkyl chain lengths of ILs on the microstructures and the tribological properties of LLCs were investigated...
March 14, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29601958/polymer-free-cubosomes-for-simultaneous-bioimaging-and-photodynamic-action-of-photosensitizers-in-melanoma-skin-cancer-cells
#15
Urszula Bazylińska, Julita Kulbacka, Judith Schmidt, Yeshayahu Talmon, Sergio Murgia
We designed novel polymer-free cubic bicontinuous liquid crystalline dispersions (cubosomes) using monoolein as molecular building block, phospholipids as stabilizers, propylene glycol as hydrotrope. Their kinetic stability was evaluated by analysing the backscattering profiles upon ageing, and the most stable formulation was chosen as potential photosensitizers delivery vehicle for photodynamic therapy (PDT) of human skin melanoma cells. Morphological and topological features of such formulation alternatively loaded with Chlorin e6 or meso-Tetraphenylporphine-Mn(III) chloride photosensitizing dyes were investigated by cryo-TEM, DLS, and SAXS...
March 20, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29599493/ring-tetramerization-is-required-for-nuclear-body-biogenesis-and-pml-sumoylation
#16
Pengran Wang, Shirine Benhenda, Haiyan Wu, Valérie Lallemand-Breitenbach, Tao Zhen, Florence Jollivet, Laurent Peres, Yuwen Li, Sai-Juan Chen, Zhu Chen, Hugues de Thé, Guoyu Meng
ProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray crystallography and SAXS characterization, we demonstrate that PML RING tetramerizes through highly conserved PML-specific sequences, which are required for NB assembly and PML sumoylation. Conserved residues implicated in RING dimerization of other TRIMs also contribute to PML tetramer stability...
March 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29596913/wing-vein-development-in-the-sawfly-athalia-rosae-is-regulated-by-spatial-transcription-of-dpp-bmp-signaling-components
#17
Yunxian Huang, Masatsugu Hatakeyama, Osamu Shimmi
Wing venation among insects serves as an excellent model to address how diversified patterns are produced. Previous studies suggest that evolutionarily conserved Decapentaplegic (Dpp)/Bone Morphogenetic Protein (BMP) signal plays a critical role in wing vein development in the Dipteran Drosophila melanogaster and the Hymenopteran sawfly Athalia rosae. In sawfly, dpp is ubiquitously expressed in the wing during prepupal stages, but Dpp/BMP signal is localized in the future vein cells. Since localized BMP signaling involves BMP binding protein Crossveinless (Cv), redistribution of BMP ligands appears to be crucial for sawfly wing vein formation...
March 26, 2018: Arthropod Structure & Development
https://www.readbyqxmd.com/read/29596046/ensemble-cryoem-elucidates-the-mechanism-of-insulin-capture-and-degradation-by-human-insulin-degrading-enzyme
#18
Zhening Zhang, Wenguang G Liang, Lucas J Bailey, Yong Zi Tan, Hui Wei, Andrew Wang, Mara Farcasanu, Virgil A Woods, Lauren A McCord, David Lee, Weifeng Shang, Rebecca Deprez-Poulain, Benoit Deprez, David R Liu, Akiko Koide, Shohei Koide, Anthony A Kossiakoff, Sheng Li, Bridget Carragher, Clinton S Potter, Wei-Jen Tang
Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type 2 diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity...
March 29, 2018: ELife
https://www.readbyqxmd.com/read/29592840/doravirine-versus-ritonavir-boosted-darunavir-in-antiretroviral-naive-adults-with-hiv-1-drive-forward-48-week-results-of-a-randomised-double-blind-phase-3-non-inferiority-trial
#19
Jean-Michel Molina, Kathleen Squires, Paul E Sax, Pedro Cahn, Johan Lombaard, Edwin DeJesus, Ming-Tain Lai, Xia Xu, Anthony Rodgers, Lisa Lupinacci, Sushma Kumar, Peter Sklar, Bach-Yen Nguyen, George J Hanna, Carey Hwang
BACKGROUND: Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. METHODS: In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries...
March 23, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29589933/structural-characterization-of-biocompatible-reverse-micelles-using-small-angle-x-ray-scattering-31-p-nuclear-magnetic-resonance-and-fluorescence-spectroscopy
#20
Emmanuel Odella, Ruben Dario Falcone, Marcelo Ceolin, Juana J Silber, N Mariano Correa
The most critical problem regarding the use of reverse micelles (RMs) in several fields is the toxicity of their partial components. In this sense, many efforts have been made to characterize non-toxic RMs formulations based on biological amphiphiles and/or different oils. In this contribution, the microstructure of biocompatible mixed RMs formulated by sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) and tri-n-octylphosphine oxide (TOPO) surfactants dispersed in the friendly solvent methyl laurate was studied by using SAXS, 31P NMR and, following the solvatochromic behavior of the molecular probe 4-aminophthalimide (4-AP)...
March 28, 2018: Journal of Physical Chemistry. B
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