Seismocardiography is the noninvasive measurement of cardiac vibrations transmitted to the chest wall by the heart during its movement. While most applications for seismocardiography are based on unidirectional acceleration measurement, several studies have highlighted the importance of three-dimensional measurements in cardiac vibration studies. One of the main challenges in using three-dimensional measurements in seismocardiography is the significant inter-subject variability of waveforms. This study investigates the feasibility of using a unified frame of reference to improve the inter-subject variability of seismocardiographic waveforms.Three-dimensional seismocardiography signals were acquired from ten healthy subjects to test the feasibility of the present method for improving inter-subject variability of three-dimensional seismocardiograms. The first frame of reference candidate was the orientation of the line connecting the points representing mitral valve closure and aortic valve opening in seismocardiograms. The second candidate was the orientation of the line connecting the two most distant points in the three dimensional seismocardiogram. The unification of the frame of reference was performed by rotating each subject's three-dimensional seismocardiograms so that the lines connecting the desired features were parallel between subjects.The morphology of the three-dimensional seismocardiograms varied strongly from subject to subject. Fixing the frame of reference to the line connecting the MC and AO peaks enhanced the correlation between the subjects in the y axis from 0.42 ± 0.30 to 0.83 ± 0.14. The mean correlation calculated from all axes increased from 0.56 ± 0.26 to 0.71 ± 0.24 using the line connecting the mitral valve closure and aortic valve opening as the frame of reference. When the line connecting the two most distant points was used as a frame of reference, the correlation improved to 0.60 ± 0.22.The results indicate that using a unified frame of reference is a promising method for improving the inter-subject variability of three-dimensional seismocardiograms. Also, it is observed that three-dimensional seismocardiograms seem to have latent inter-subject similarities, which are feasible to be revealed. Because the projections of the cardiac vibrations on the measurement axes differ significantly, it seems obligatory to use three-dimensional measurements when seismocardiogram analysis is based on waveform morphology.
The data used for publication "Partitioning of Catechol Derivatives in Lipid Membranes: Implications for Substrate Specificity to Catechol-O-methyltransferase" in ACS Chemical Neuroscience (2020), 11(6), 969-978.
Abstract In a healthcare setting, biofilms are a major source of infection and difficult to eradicate once formed. Nanoparticles (NPs) can be designed to effectively penetrate biofilms to more efficiently either deliver antibiotic drugs throughout the biofilm matrix or elicit inherent antibiofilm activity. Antibacterial cerium oxide (CeO 2 ) NPs were employed as core material and coated with a mesoporous silica shell (MSN) to generate cerium oxide coated mesoporous silica NPs (CeO 2 @MSN). Detailed studies of NP‐biofilm interactions are required to rationally develop NP platforms to prevent biofilm‐related infections. This work developed and implemented a unique label‐free analysis platform for the real‐time monitoring of bacterial biofilm formation and then assessed the interactions of antibacterial NPs. An analysis platform which allows bacterial biofilms to grow and develop in situ in flow within the multi‐parametric surface plasmon resonance (MP‐SPR) instrument was established. This enabled simultaneous monitoring and detection of biofilm growth phases, structure, and interactions between differentially charged CeO 2 @MSNs and bacterial biofilms. Positively charged antibacterial NPs (polyethyleneimine functionalized CeO 2 @MSNs) were found to be the most efficient to penetrate the biofilm. The MP‐SPR analysis platform was shown to be a powerful tool for monitoring biofilm development in real‐time and to analyze biofilm properties and NP‐biofilm interactions.
The data used for publication "Partitioning of Catechol Derivatives in Lipid Membranes: Implications for Substrate Specificity to Catechol-O-methyltransferase" in ACS Chemical Neuroscience (2020), 11(6), 969-978.
Abstract Deciphering the extracellular vesicle (EV) heterogeneity is essential for understanding their biological functions and enhancing their utility in drug development and medical diagnostics. Here, we demonstrate the efficacy of label-free surface-based waveguide scattering microscopy, coupled with multiplexed fluorescence readout, for quantifying size, inner cargo concentration, and surface protein markers at the individual EV level. By modulating the optical contrast between EVs and the surrounding medium using membrane-permeable and -impermeable solutes, we identify subpopulations of low-cargo EVs and cell-specific markers for EVs derived from platelets and red blood cells. Time-resolved label-free antibody binding to single blood-derived EVs reveals variations in binding rates and facilitates the quantification of surface protein marker density. Additionally, we observe that the presence of tetraspanins, well-known EV markers, correlates with biomolecular content but not size. These findings highlight the crucial role of time-resolved surface-based quantitative EV analysis in complementing current methodologies, offering unparalleled insights into EV characterization.
Characterization of nanoparticles (NPs) and their subpopulations in heterogeneous samples is of utmost importance, for example, during the initial design of targeted NP therapies and the different phases of their production cycle. This work presents a general antibody-mediated surface capture and analysis protocol for NPs using a Protein A/G-functionalized surface plasmon resonance biosensor. The use of anti-streptavidin antibodies allows regenerable capture of biotin-containing NPs such as large unilamellar vesicles commonly used as drug delivery vehicles. Furthermore, the use of antibodies directed against glycophorin A and B enabled diffusion-limited surface capture of red blood cell-derived extracellular vesicles (RBC EVs). RBC EVs showed the efficacy of the biosensor in the determination of size and bulk concentration of NP subpopulations isolated from a complex biological matrix. The mean size of the surface-captured RBC EVs was comparable to the corresponding sizes derived for the entire EV population measured with well-established NP sizing techniques, namely, nanoparticle tracking analysis and dynamic light scattering. Taken together, the Protein A/G-functionalized biosensor provides a generic alternative to the existing NP-capturing sensors based on, for example, covalent antibody attachment, hydrophobic surfaces or biotin-capped self-assembled monolayers.
The enzyme catechol-O-methyltransferase (COMT) has water soluble (S-COMT) and membrane associated (MB-COMT), bitopic, isoforms. Of these MB-COMT is a drug target in relation to the treatment of Parkinson's disease. Using a combination of computational and experimental protocols, we have determined the substrate selection mechanism specific to MB-COMT. We show: (1) substrates with preferred affinity for MB-COMT over S-COMT orient in the membrane in a fashion conducive to catalysis from the membrane surface and (2) binding of COMT to its cofactor ADOMET induces conformational change that drives the catalytic surface of the protein to the membrane surface, where the substrates and Mg2+ ions, required for catalysis, are found. Bioinformatics analysis reveals evidence of this mechanism in other proteins, including several existing drug targets. The development of new COMT inhibitors with preferential affinity for MB-COMT over S-COMT is now possible and insight of broader relevance, into the function of bitopic enzymes, is provided.
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