2013-2014 Dean\u27s Showcase no. 4

https://spiral.lynn.edu/conservatory_deansshowcase/1017/thumbnail.jp

Valuation of Green Walls and Green Roofs as Soundscape Measures: Including Monetised Amenity Values Together with Noise-attenuation Values in a Cost-benefit Analysis of a Green Wall Affecting Courtyards

Economic unit values of soundscape/acoustic effects have been based on changes in the number of annoyed persons or on decibel changes. The normal procedure has been the application of these unit values to noise-attenuation measures affecting the noisier façade of a dwelling. Novel modular vegetation-based soundscape measures, so-called green walls, might be relevant for both noisy and quieter areas. Moreover, their benefits will comprise noise attenuation as well as non-acoustic amenity effects. One challenge is to integrate the results of some decades of non-acoustic research on the amenity value of urban greenery into design of the urban sound environment, and incorporate these non-acoustic properties in the overall economic assessment of noise control and overall sound environment improvement measures. Monetised unit values for green walls have been included in two alternative cases, or demonstration projects, of covering the entrances to blocks of flats with a green wall. Since these measures improve the noise environment on the quiet side of the dwellings and courtyards, not the most exposed façade, adjustment factors to the nominal quiet side decibel reductions to arrive at an estimate of the equivalent overall acoustic improvement have been applied. A cost-benefit analysis of the green wall case indicates that this measure is economically promising, when valuing the noise attenuation in the quieter area and adding the amenity/aesthetic value of the green wall

2013-2014 Dean\u27s Showcase No. 2

https://spiral.lynn.edu/conservatory_deansshowcase/1015/thumbnail.jp

Cholesterol loading reprograms the microRNA-143/145-Myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype

OBJECTIVE: We previously showed that cholesterol loading in vitro converts mouse aortic vascular smooth muscle cells (VSMC) from a contractile state to one resembling macrophages. In human and mouse atherosclerotic plaques it has become appreciated that ~40% of cells classified as macrophages by histological markers may be of VSMC origin. We therefore sought to gain insight into the molecular regulation of this clinically relevant process. APPROACH AND RESULTS: VSMC of mouse (or human) origin were incubated with cyclodextrin-cholesterol complexes for 72 hours, at which time the expression at the protein and mRNA levels of contractile-related proteins were reduced and of macrophage markers increased. Concurrent was down regulation of miR-143/145, which positively regulate the master VSMC-differentiation transcription factor myocardin (MYOCD). Mechanisms were further probed in mouse VSMC. Maintaining the expression of MYOCD or miR-143/145 prevented and reversed phenotypic changes caused by cholesterol loading. Reversal was also seen when cholesterol efflux was stimulated after loading. Notably, despite expression of macrophage markers, bioinformatic analyses showed that cholesterol-loaded cells remained closer to the VSMC state, consistent with impairment in classical macrophage functions of phagocytosis and efferocytosis. In apoE-deficient atherosclerotic plaques, cells positive for VSMC and macrophage markers were found lining the cholesterol-rich necrotic core. CONCLUSIONS: Cholesterol loading of VSMC converts them to a macrophage–appearing state by downregulating the miR-143/145-myocardin axis. Though these cells would be classified by immunohistochemistry as macrophages in human and mouse plaques, their transcriptome and functional properties imply that their contributions to atherogenesis would not be those of classical macrophages

A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism

We have investigated delivery of protein therapeutics from the bloodstream into the brain using a mouse model of late-infantile neuronal ceroid lipofuscinosis (LINCL), a lysosomal disease due to deficiencies in tripeptidyl peptidase 1 (TPP1). Supraphysiological levels of TPP1 are delivered to the mouse brain by acute intravenous injection when co-administered with K16ApoE, a peptide that in trans mediates passage across the blood-brain barrier (BBB). Chronic treatment of LINCL mice with TPP1 and K16ApoE extended the lifespan from 126 to \u3e294 days, diminished pathology, and slowed locomotor dysfunction. K16ApoE enhanced uptake of a fixable biotin tracer by brain endothelial cells in a dose-dependent manner, suggesting that its mechanism involves stimulation of endocytosis. Pharmacokinetic experiments indicated that K16ApoE functions without disrupting the BBB, with minimal effects on overall clearance or uptake by the liver and kidney. K16ApoE has a narrow therapeutic index, with toxicity manifested as lethargy and/or death in mice. To address this, we evaluated variant peptides but found that efficacy and toxicity are associated, suggesting that desired and adverse effects are mechanistically related. Toxicity currently precludes direct clinical application of peptide-mediated delivery in its present form but it remains a useful approach to proof-of-principle studies for biologic therapies to the brain in animal models

Cholesterol Loading Reprograms the MicroRNA-143/145–Myocardin Axis to Convert Aortic Smooth Muscle Cells to a Dysfunctional Macrophage-Like Phenotype

OBJECTIVE: We previously showed that cholesterol loading in vitro converts mouse aortic vascular smooth muscle cells (VSMC) from a contractile state to one resembling macrophages. In human and mouse atherosclerotic plaques it has become appreciated that ~40% of cells classified as macrophages by histological markers may be of VSMC origin. We therefore sought to gain insight into the molecular regulation of this clinically relevant process. APPROACH AND RESULTS: VSMC of mouse (or human) origin were incubated with cyclodextrin-cholesterol complexes for 72 hours, at which time the expression at the protein and mRNA levels of contractile-related proteins were reduced and of macrophage markers increased. Concurrent was down regulation of miR-143/145, which positively regulate the master VSMC-differentiation transcription factor myocardin (MYOCD). Mechanisms were further probed in mouse VSMC. Maintaining the expression of MYOCD or miR-143/145 prevented and reversed phenotypic changes caused by cholesterol loading. Reversal was also seen when cholesterol efflux was stimulated after loading. Notably, despite expression of macrophage markers, bioinformatic analyses showed that cholesterol-loaded cells remained closer to the VSMC state, consistent with impairment in classical macrophage functions of phagocytosis and efferocytosis. In apoE-deficient atherosclerotic plaques, cells positive for VSMC and macrophage markers were found lining the cholesterol-rich necrotic core. CONCLUSIONS: Cholesterol loading of VSMC converts them to a macrophage–appearing state by downregulating the miR-143/145-myocardin axis. Though these cells would be classified by immunohistochemistry as macrophages in human and mouse plaques, their transcriptome and functional properties imply that their contributions to atherogenesis would not be those of classical macrophages