Search bioRxiv⌕ Search

Biology subjects

Oh, B.

Publications and source records attributed to Oh, B..

2 recordsLinked to original sources

In-situ microscopy-assisted meniscus-guided coating for highly sensitive reduced graphene oxide-based nanocomposite biosensor

Meniscus-guided coating provides great potential for fabricating the nanomaterial-based thin film into high-performance biomedical devices due to the strong relationship between its experimental parameters and the resulting structural properties. However, the complex leverages of various fluid dynamics phenomena hamper optimization of structural properties and device performances. This is due to the absence of in-depth analytical techniques to observe, interpret, and control the solidification process. In this work, we propose an analytical strategy based on the rheological properties of a rGO-based solution using computational fluid dynamics modeling and in situ high-speed microscopy. Through this, we reveal the principles of the solidification mechanism that creates a rGO-based nanocomposite in the form of highly- and evenly-wrinkled thin film and the experimental condition at which this mechanism occurs. The optimized thin film presents high electroconductivity, low chip-to-chip signal variation, and multiplexed electrochemical biosensing performance for three classes of antibodies related to the excessive enrichment of endoplasmic reticulum stress, with detection limits of picomolar levels. This optimizing technique can be universally applied to understanding various solution-based coating systems, and can streamline the production of large-area and high-quality nanocomposite biosensors.

bioengineering↗

Enlarged Perivascular Spaces are Associated with White Matter Injury, Brain Atrophy, Cognitive Decline and Markers of Inflammation in an Autosomal Dominant Vascular Neurodegenerative Disease (CADASIL)

Background and ObjectivesEnlarged perivascular spaces (ePVS) have been previously reported in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL), but their significance and pathophysiology remains unclear. We investigated associations of ePVS with classical imaging measures, cognitive measures and plasma proteins to better understand what ePVS represents in CADASIL and whether radiographic measures of ePVS would be of value in future therapeutic discovery studies for CADASIL. Methods24 individuals with CADASIL and 24 age and sex matched controls were included. Disease status was determined based on presence of NOTCH3 mutation. Brain imaging measures of white matter hyperintensity (WMH), brain parenchymal fraction (BPF), ePVS volumes, clinical, and cognitive measures, as well as plasma proteomics were used in models. Global ePVS volumes were calculated via a novel, semi-automated pipeline and levels of 7363 proteins were quantified in plasma using the SomaScan assay. The relationship of ePVS with global burden of WMH, brain atrophy, functional status, neurocognitive measures, and plasma proteins were modelled with linear regression models. ResultsCADASIL and control groups did not exhibit differences in mean ePVS volumes. However, increased ePVS volumes in CADASIL were associated with increased WMH volume ({beta}=0.57, p=0.05), Clinical Dementia Rating (CDR) Sum-of-Boxes score ({beta}=0.49, p=0.04), and decreased brain parenchymal fraction (BPF) ({beta}=-0.03, p=0.10). In interaction term models, the interaction term between CADASIL disease status and ePVS volume was associated with increased WMH volume ({beta}=0.57, p=0.02), Clinical Dementia Rating (CDR) Sum-of-Boxes score ({beta}=0.52, p=0.02), decreased BPF ({beta}=-0.03, p=0.07) and Mini Mental State Examination (MMSE) score ({beta}=-1.49, p=0.03). Proteins positively associated with ePVS volumes were found to be related to leukocyte migration and inflammation, while negatively associated proteins were related to lipid metabolism. Two central hub proteins were identified in protein networks associated with ePVS volumes: CXCL8/IL-8, and CCL2/MCP-1. The levels of CXCL8/IL8 were also associated with increased WMH volume ({beta}=2.44, p < 0.01), and levels of CCL2/MCP-1 were further associated with decreased BPF ({beta}=-0.0007, p < 0.01), MMSE score ({beta}=-0.02, p < 0.01), and increased Trail Making Test B (TRAILB) completion time ({beta}=0.76, p < 0.01). No protein was associated with all 3 studied imaging measures of pathology (BPF,ePVS,WMH). DiscussionBased on associations uncovered between ePVS volumes and cognitive functions, imaging and plasma proteins, we conclude that ePVS volumes capture pathologies contributing to chronic brain dysfunction and degeneration in CADASIL, with relevance to future clinical trials for novel therapeutic discoveries to prevent decline and injury in individuals carrying NOTCH3 mutations.

neuroscience↗