Engineered functional neural interfaces (fNIs) serve as essential abiotic–biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular ...signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms. fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.
Abstract only Heart disease remains the leading cause of death in the United States with heart failure specifically accounting for 13.4% of all heart disease related deaths. In 2019, Andersson et ...al., utilized a multi-omics approach to evaluate participant samples from the Framingham Heart Study and showed that ankyrin-R (AnkR; encoded by ANK1 ) is significantly associated with diastolic function, left ventricular remodeling and heart failure with preserved ejection fraction. Ankyrins are a family of proteins that link integral membrane proteins with the actin/β-spectrin cytoskeleton. Ankyrins-B/G have been extensively studied and identified within the heart and their dysfunction is associated with cardiac structural and electrical phenotypes. Ankyrin-R was first identified in red blood cells and has yet to be studied in the context of cardiac function and heart failure or arrhythmia disease. To study AnkR in the context of the heart we isolated perfused tissues from adult wild-type mice and performed immunoblot and qPCR analysis on ankyrin-R protein and Ank1 mRNA expression. The large AnkR isoform is expressed in the heart, along with the brain, intestine, and spleen. Interestingly, only the heart showed expression of a small AnkR isoform that has previously been shown to interact with the sarcoplasmic protein obscurin. Notably, isolated cardiomyocytes express the small AnkR isoform while cardiac fibroblasts express the canonical large AnkR isoform at both the protein and mRNA level. Canonical AnkR is diffusely expressed in the fibroblast membrane, cytoplasm, cytoskeleton, and soluble nuclear fractions. Interestingly, this expression pattern is switched under stressed conditions where cardiomyocytes increase and cardiac fibroblasts decrease their canonical AnkR expression, respectively. These preliminary results are the first to show canonical AnkR expression in the mouse myocardium specifically within the cardiac fibroblasts and allude that AnkR’s utilization during cardiac stress is cell-type dependent. Future studies will seek to define molecular, cell, and organ phenotypes related to AnkR in the heart.
One-dimensional zinc oxide (ZnO) nanostructure arrays show unique semiconducting, piezoelectric, and wetting properties, and how they interact with cells is critical for their biomedical ...applications. In this work, we prepare ZnO nanorod arrays (ZnO NRAs) and study their interactions with neonatal rat cardiomyocytes either as a substrate or patch. We find that ZnO NRAs can (1) inhibit cell adhesion and spreading as a substrate and (2) selectively kill underneath cells as a patch. We further identify surface nanomorphology as the dominant factor responsible for the inhibitory effect. These discoveries suggest potential application of ZnO NRAs as a cell inhibitory biointerface.
Abstract only Introduction: Cardiovascular disease (CVD) is the leading cause of death in the U.S., where coronary artery disease (CAD) accounts for 42.1% of all CVD deaths. Current therapeutics ...focus on lowering LDL-C, as previous attempts to raise HDL-C were not successful in altering CVD outcomes. However, the therapeutic potential of HDL has not been fully explored. Variants in SCARB1, the gene that encodes HDL receptor Scavenger Receptor B1 (SR-BI), are associated with dyslipidemia and atherosclerotic CVD (ASCVD), and we first to identified Mendelian inheritance of SCARB1 variants that cause severe early-onset CAD and dyslipidemia. Limited clinical evidence suggests imatinib reduces total cholesterol in chronic myeloid leukemia (CML). Additionally, TKI treatment in atherosclerotic mice reduced total cholesterol (imatinib) and atherosclerotic lesions (dasatinib). Yet, no data is available on the effects of TKIs on HDL and RCT. Hypothesis: Our findings suggest that HDL function (vs. HDL-C concentration) in reverse cholesterol transport (RCT) may be a promising target for cholesterol-based therapy and studying TKIs in RCT may provide a novel mechanism for therapeutic development. Methods: We performed a high throughput drug screen with 788 FDA-approved compounds, using HepG2 cells to measure endogenous HDL binding. We identified four compounds that significantly increased HDL binding, of which, imatinib was the only one to increase SR-BI. Wildtype C57Bl/6 mice on a high fat, high cholesterol diet, underwent imatinib treatment for 4 weeks and measured biweekly serum lipids. Results: We have found that imatinib and dasatinib significantly enhance HDL binding, where imatinib increased SR-BI, ABCA1, and ABCG1 in vitro. Furthermore, in vivo imatinib treatment decreased plasma total cholesterol, HDL-C and triglyceride levels, and elevated hepatic SR-BI. Knockdown of SR-BI in HepG2 cells ameliorated the imatinib-induced HDL binding increase suggesting an SR-BI-specific mechanism. Mass spectrometry revealed a novel SR-BI methionine oxidation site with imatinib treatment. Conclusions: Our data supports the exploration of TKI-mediated SR-B1 regulation, HDL metabolism, and RCT mechanism to identify new therapeutic targets for dyslipidemia and ASCVD.
Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified ...in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.
Highly branched perfluorinated aromatic polyether copolymers were prepared from the polycondensation of the AB sub(2) monomer, 3,5-bis(pentafluorobenzyl)oxybenzyl alcohol with a variety of fluoroaryl ...and alkyl bromide AB comonomers. The structures and comonomer distribution of the resulting polymers were characterized in detail. super(1)H NMR data from kinetic trials illustrated that perfluoroaryl AB comonomer distribution correlated to AB comonomer sterics. super(19)F NMR data revealed that fluorinated AB monomers and 3-bromo-1-propanol AB monomers were distributed within the AB sub(2) polymer backbone, while longer alkyl bromide AB monomers, 6-bromo-1-hexanol, were mostly distributed along hyperbranched polymer chain ends. In general, as AB comonomer incorporation increased for nonsterically hindered copolymers, thermal decomposition onset increased and glass transition temperatures decreased. The combined data demonstrated the effect of comonomer distribution and sterics on physical properties of AB sub(2)-based polymer systems. The resulting materials were used to cast thin polymer films for measurement of contact angle, which were shown to be directly related to comonomer content. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1880-1894 Several highly branched copolymer systems were prepared from AB sub(2)+AB polycondensations of perfluorinated benzyl-alcohol-bearing monomers and alkyl primary alcohol-bearing comonomers. The resulting copolymers were fully characterized. It was found that the extent of comonomer incorporation was dependent on comonomer sterics, acidity of the alcohol, and feed ratio of each monomer. In general the glass transition temperature decreased and thermal stability increased with incorporation of an AB monomer into the AB sub(2) system.
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