Biology subjects

Lee, D. S.

Publications and source records attributed to Lee, D. S..

5 recordsLinked to original sources

bioRxiv2018

Graphene-oxide quenching-based molecular beacon imaging of exosome-mediated transfer of neurogenic miR-193a on microfluidic platform

A microRNA (miR-193a) was found to be transferred in the exosomes of differentiated neural progenitors to undifferentiated clones. Graphene-oxide (GO) quenching-based molecular beacon was developed to detect RNAs in living cells and tissues quickly and sensitively. Here, we applied GO quencher-based molecular beacon sensor to visualize neurogenic miR-193a levels delivered via exosome during cell-non-autonomous neurogenesis of neural progenitor cells on microfluidic platform. Fluorescence signals of FAM-labeled peptide nucleic acid (PNA) against miR-193a quenched by GO nanosheets (FAM-PNA193a-GO) were recovered in undifferentiated recipient cells differentiated to the neuronal lineage by exosome-mediated neurogenesis 3 days after co-culture with differentiated donor cells. We propose that molecular beacon imaging using PNA-GO complex can be used to visualize individual cellular expression of mature microRNAs revealing their precise spatial localization and temporal sequences by the intercellular exosome delivery of messages to undergo processes such as cell-non-autonomous neurogenesis.

cell biology↗

bioRxiv2017

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months

ObjectiveFunctional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. Methods: This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants (n=65, included in final analyses: n=53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 minutes of fcMRI acquired during natural sleep at term-equivalent age.\n\nResultsDisruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course.\n\nConclusionfcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

neuroscience↗

bioRxiv2017

Predicting aging of brain metabolic topography using variational autoencoder

Predicting future brain topography can give insight into neural correlates of aging and neurodegeneration. Due to variability in aging process, it has been challenging to precisely estimate brain topographical change according to aging. Here, we predict age-related brain metabolic change by generating future brain 18F-Fluorodeoxyglucose PET. A cross-sectional PET dataset of cognitively normal subjects with different age was used to develop a generative model. The model generated PET images using age information and characteristic individual features. Predicted regional metabolic changes were correlated with the real changes obtained by follow-up data. This model was applied to produce a brain metabolism aging movie by generating PET at different ages. Normal population distribution of brain metabolic topography at each age was estimated as well. In addition, a generative model using APOE4 status as well as age as inputs revealed a significant effect of APOE4 status on age-related metabolic changes particularly in the calcarine, lingual cortex, hippocampus and amygdala. It suggested APOE4 could be a factor affecting individual variability in age-related metabolic degeneration in normal elderly. This predictive model may not only be extended to understanding cognitive aging process, but apply to development of a preclinical biomarker for various brain disorders.

neuroscience↗

bioRxiv2017

Graphene Oxide-Quenching-Based Fluorescence In Situ Hybridization (G-FISH) To Detect RNA In Tissue: Simple And Fast Tissue RNA Diagnostics

FISH-based RNA detection in paraffin-embedded tissue can be challenging, with complicated procedures producing uncertain results and poor image quality. Here, we developed a robust RNA detection method based on graphene oxide (GO) quenching and recovery of fluorescence in situ hybridization (G-FISH) in formalin-fixed paraffin-embedded (FFPE) tissues. Using G-FISH technique, the long noncoding BC1 RNA, {beta}-actin mRNA, miR-124a and miR-21 could be detected in the cytoplasm of a mouse brain, primary hippocampal neurons, and glioblastoma multiforme tumor tissues, respectively. G-FISH showed the increased BC1 RNA level in individual hippocampal neurons of Alzheimers disease brain. The fluorescence recovered by G-FISH correlated highly with the amount of miR-21, as measured by real time RT-PCR. We propose G-FISH as a simple, fast, inexpensive, and sensitive method for RNA detection, with very low background, which could be applied to a variety of researches or diagnostic purposes.

molecular biology↗

bioRxiv2017

Differences in the spatial and temporal patterns of head motion during MRI of adults and infants

AimHead motion has a profound effect on MRI, and will contaminate comparisons of function or structure between groups that move differently. This work compares adults and infants. Infants might move differently for physical, physiological and cognitive reasons, but so far these differences have not been quantified.\n\nMethodsThe spatial modes and total magnitude of motion in the MRI scanner were measured (N=211). The effects of group (infant vs. adult) and stimulation paradigm (auditory vs. visual) were evaluated.\n\nResultsSpatial modes of motion were found to be distinct between infant and adult groups. Infants had less anterior-posterior translational motion, but greater motion in other dimensions, often with complex multi-axis patterns. In magnitude distribution, sleeping infants often remained more still than adults, but when movement did occur it was more extreme and abrupt. Two groups of adults presented with different stimulation showed similar shapes of motion.\n\nConclusionThe spatial modes and magnitude distribution of motion differed substantially between groups, and must be considered carefully as a confound in comparisons of structure or function. The abruptness and magnitude of movement suggests that for infants relative to adults post-processing strategies such as de-noising are likely to be more effective than prospective motion correction.\n\nKey notesO_LIQuantified the spatial and temporal distribution of motion during MRI in 211 adults and neonates\nC_LIO_LIThe different spatial modes in adults and infants were visualized and statistically contrasted\nC_LIO_LIThe magnitude of motion had \"heavier tails\" in infants, with more still periods, and more large movements, than adults.\nC_LI

neuroscience↗