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In this review, we will highlight technologies that enable scientists to study the molecular characteristics of tissues and/or cells without the need for antibodies or other labeling techniques. Specifically, we will focus on matrix-assisted laser desorption/ionization imaging mass spectrometry, infrared spectroscopy, and Raman spectroscopy.
Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Amyloid fibril polymorphism is not well understood despite its potential importance for biological activity and associated toxicity. Controlling the polymorphism of mature fibrils including their morphology and supramolecular chirality by postfibrillation changes in the local environment is the subject of this study. Specifically, the effect of pH on the stability and dynamics of HET-s (218-289) prion fibrils has been determined through the use of vibrational circular dichroism (VCD), deep UV resonance Raman, and fluorescence spectroscopies. It was found that a change in solution pH causes deprotonation of Asp and Glu amino acid residues on the surface of HET-s (218-289) prion fibrils and triggers rapid transformation of one supramolecular chiral polymorph into another. This process involves changes in higher order arrangements like lateral filament and fibril association and their supramolecular chirality, while the fibril cross-β core remains intact. This work suggests a hypothetical mechanism for HET-s (218-289) prion fibril refolding and proposes that the interconversion between fibril polymorphs driven by the solution environment change is a general property of amyloid fibrils.
Using the 6,6'-dibromo-[1,1'-binaphthalene]-2,2'-diol molecule and its vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra measured in deuterated dimethyl sulfoxide as example, we present a first detailed study of the effects induced in VCD spectra by the large-amplitude motions of solvent molecules loosely bound to a solute molecule. We show that this type of perturbation can induce significant effects in the VA and VCD spectra. We also outline a computational procedure that can effectively model the effects induced in the spectra and at the same time provide detailed structural information regarding the relative orientations of moieties involved in a solute-solvent molecular complex.
We present a systematic, multiparameter study of Rb/(129)Xe spin-exchange optical pumping (SEOP) in the regimes of high xenon pressure and photon flux using a 3D-printed, clinical-scale stopped-flow hyperpolarizer. In situ NMR detection was used to study the dynamics of (129)Xe polarization as a function of SEOP-cell operating temperature, photon flux, and xenon partial pressure to maximize (129)Xe polarization (PXe). PXe values of 95 ± 9%, 73 ± 4%, 60 ± 2%, 41 ± 1%, and 31 ± 1% at 275, 515, 1000, 1500, and 2000 Torr Xe partial pressure were achieved. These PXe polarization values were separately validated by ejecting the hyperpolarized (129)Xe gas and performing low-field MRI at 47.5 mT. It is shown that PXe in this high-pressure regime can be increased beyond already record levels with higher photon flux and better SEOP thermal management, as well as optimization of the polarization dynamics, pointing the way to further improvements in hyperpolarized (129)Xe production efficiency.
The process of bone healing requires the restoration of both anatomy and physiology, and there is a recognized need for innovative biomaterials that facilitate remodeling throughout this complex process. While porous scaffolds with a high degree of interconnectivity are known to accelerate cellular infiltration and new bone formation, the presence of pores significantly diminishes the initial mechanical properties of the materials, rendering them largely unsuitable for load-bearing applications. In this study, a family of non-porous composites has been fabricated by reactive compression molding of mineralized allograft bone particles (MBPs) with a biodegradable polyurethane (PUR) binder, which is synthesized from a polyester polyol and a lysine-derived polyisocyanate. At volume fractions exceeding the random close-packing limit, the particulated allograft component presented a nearly continuous osteoconductive pathway for cells into the interior of the implant. By varying the molecular weight of the polyol and manipulating the surface chemistry of the MBP via surface demineralization, compressive modulus and strength values of 3-6 GPa and 107-172 MPa were achieved, respectively. When implanted in bilateral femoral condyle plug defects in New Zealand White rabbits, MBP/PUR composites exhibited resorption of the allograft and polymer components, extensive cellular infiltration deep into the interior of the implant, and new bone formation at 6 weeks. While later in vivo timepoints are necessary to determine the ultimate fate of the MBP/PUR composites, these observations suggest that allograft bone/polymer composites have potential for future development as weight-bearing devices for orthopedic applications.
Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.