Background: CSF infection is a significant complication of ventriculoperitoneal (VP) shunts and results in prolonged hospital stay, developmental delay and decreased quality of life. To decrease the high rates of neonatal VP shunt infections, an updated clinical guideline that included the use of antibiotic-impregnated shunts and a revised peri-operative antibiotic protocol was introduced in our neonatal unit. In this study, we evaluated the efficacy of these new guidelines in reducing the CSF shunt infection rates.
View Article and Find Full Text PDFGuanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) function in complexes with a range of molecules and proteins including ligands, G proteins, arrestins, ubiquitin, and other receptors. Elements of these complexes may interact constitutively or dynamically, dependent upon factors such as ligand binding, phosphorylation, and dephosphorylation. They may also be allosterically modulated by other proteins in a manner that changes temporally and spatially within the cell.
View Article and Find Full Text PDFBackground And Purpose: The orexin system regulates a multitude of key physiological processes, particularly involving maintenance of metabolic homeostasis. Consequently, there is considerable potential for pharmaceutical development for the treatment of disorders from narcolepsy to metabolic syndrome. It acts through the hormonal activity of two endogenous peptides, orexin A binding to orexin receptors 1 and 2 (OX₁ and OX₂) with similar affinity, and orexin B binding to OX₂ with higher affinity than OX₁ receptors.
View Article and Find Full Text PDFOrexin G protein-coupled receptors (OxRs) and their cognate agonists have been implicated in a number of disorders since their recent discovery, ranging from narcolepsy to formation of addictive behavior. Bioluminescence resonance energy transfer assays of agonist-occupied OxRs provided evidence for a strong dose-dependent interaction with both trafficking proteins β-arrestin 1 and 2 that required unusually high agonist concentrations compared with inositol phosphate signaling. This appears to be reflected in functional differences in potency with respect to orexin A (OxA) and OxR2-dependent ERK1/2 phosphorylation after 90 min compared with 2 min, potentially consistent with β-arrestin-mediated versus G protein-mediated signaling, respectively.
View Article and Find Full Text PDFMesophase separation has been identified in a polycation/anionic-nonionic mixed micelle system formed by the coacervation of poly(diallyldimethylammoniumchloride)/sodium dodecylsulfate-Triton X-100 in 0.40 M NaCl. The resultant dense, optically clear fluid was studied by turbidity, dynamic light scattering (DLS), and rheology.
View Article and Find Full Text PDFProton pulsed field gradient (PFG) NMR was used to study the diffusion of poly(diallyldimethylammonium chloride) (PDADMAC) in coacervates formed from this polycation and the protein bovine serum albumin (BSA). Application of high (up to 30 T/m) magnetic field gradients in PFG NMR measurements allowed probing the diffusion of PDADMAC on a length scale of displacements as small as 100 nm in coacervates formed at different pH's and ionic strengths, i.e.
View Article and Find Full Text PDFElectrostatic interactions between synthetic polyelectrolytes and proteins can lead to the formation of dense, macroion-rich liquid phases, with equilibrium microheterogeneities on length scales up to hundreds of nanometers. The effects of pH and ionic strength on the rheological and optical properties of these coacervates indicate microstructures sensitive to protein-polyelectrolyte interactions. We report here on the properties of coacervates obtained for bovine serum albumin (BSA) with the biopolyelectrolyte chitosan and find remarkable differences relative to coacervates obtained for BSA with poly(diallyldimethylammonium chloride) (PDADMAC).
View Article and Find Full Text PDFThe effect of temperature on the phase behavior of a polycation-anionic/nonionic mixed micelle system, poly(dimethyldiallylammonium chloride)-sodium dodecylsulfate/Triton X-100, was studied over a wide range of surfactant compositions, ionic strengths, and polycation molecular weights using turbidimetry and dynamic light scattering. Soluble complexes become biphasic upon heating through either liquid-liquid (coacervation) or liquid-solid (precipitation) separation. The biphasic boundary comprises two regions: a coacervate domain exhibiting a lower critical solution temperature and a second superimposed domain in which either solids or very dense and viscous fluids are formed upon heating.
View Article and Find Full Text PDFWe developed a simple contrasting procedure to improve the AFM visualization of single positively charged polymer chains deposited on substrates of a relatively high roughness via the decoration of the molecules with hexacyanoferrate anions or negatively charged clusters of cyanide-bridged complexes.
View Article and Find Full Text PDFColloidal probe microscopy was employed to study forces between cellulose surfaces upon addition of a series of cationic copolymers in aqueous solution, as model compounds for wet strength agents. The content of quaternary ammonium groups and primary amines was systematically varied in the cationic polymers, to distinguish between the importance of electrostatical and H-bonding effects. Cellulose microspheres were glued at the apex of tipless microfabricated cantilevers and used as colloidal probes.
View Article and Find Full Text PDFWe show that hydrophobic flexible polyelectrolyte molecules of poly(2-vinylpyridine) and poly(methacryloyloxyethyl dimethylbenzylammonium chloride) are trapped and frozen due to adsorption on the mica surface, and the observed AFM single molecule structures reflect the molecular conformation in solution. An increase of the ionic strength of the solution induces the cascade of abrupt conformational transitions due to the intrachain segregation from elongated coil to compact globule conformations through intermediate pearl necklace-globule conformations with different amounts of beads per chain. The length of the necklaces and the number of beads decrease, while the diameter of beads increases with the increase of ionic strength.
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