Biology subjects

Sung, H.

Publications and source records attributed to Sung, H..

3 recordsLinked to original sources

bioRxiv2021

The omega-3-fatty acid docosahexaenoic acid modulates intracellular myo-inositol and its biosynthetic genes.

Bipolar disorder is a debilitating mood disorder characterized by recurring episodes of mania and depression. It affects 2.6% of adults and has a lifetime prevalence among adults of 3.9%. Current mood stabilizers are not always effective and/or are not well tolerated by many patients; thus, there is a need to develop or identify more effective and less harmful treatments. Omega-3-fatty acids have been shown to be effective in the treatment of bipolar disorder; however, their mechanism of action is unknown. Myo-inositol depletion has been hypothesized as the mechanism by which mood stabilizers exert their therapeutic effect. Using an enzymatic assay, we determined intracellular myo-inositol levels increased more than 2-fold when cells were grown in the presence of the omega-3 fatty acid docosahexaenoic acid (DHA). RT-qPCR was used to characterize the effects of DHA on genes in the myo-inositol biosynthetic pathway. We show DHA increases relative expression and has a concentration-dependent impact on INO1 and INM1, which encode myo-inositol-1-phosphate synthase and myo-inositol monophosphate 1-phosphatase, respectively. We therefore conclude that the omega-3-fatty acid DHA exerts its therapeutic effect on bipolar disorder by increasing intracellular myo-inositol, which may be accomplished by upregulating its biosynthetic genes.

molecular biology↗

bioRxiv2020

TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS

Disrupted nucleocytoplasmic transport (NCT) has been implicated in neurodegenerative disease pathogenesis; however, the mechanisms by which impaired NCT causes neurodegeneration remain unclear. In a Drosophila screen, we identified Ref(2)p/p62, a key regulator of autophagy, as a potent suppressor of neurodegeneration caused by the GGGGCC hexanucleotide repeat expansion (G4C2 HRE) in C9orf72 that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that p62 is increased and forms ubiquitinated aggregates due to decreased autophagic cargo degradation. Immunofluorescence and electron microscopy of Drosophila tissues demonstrate an accumulation of lysosome-like organelles that precedes neurodegeneration. These phenotypes are partially caused by cytoplasmic mislocalization of Mitf/TFEB, a key transcriptional regulator of autophagolysosomal function. Additionally, TFEB is mislocalized and downregulated in human cells expressing GGGGCC repeats and in C9-ALS patient motor cortex. Our data suggest that the C9orf72-HRE impairs Mitf/TFEB nuclear import, thereby disrupting autophagy and exacerbating proteostasis defects in C9-ALS/FTD.

cell biology↗

bioRxiv2020

Comparative Evaluation of cobas Influenza A/B & RSV and Simplexa Flu A/B & RSV for Rapid Detection of Influenza and Respiratory Syncytial Viruses

We compared two molecular point-of-care tests, the cobas Influenza A/B & RSV (cobas Liat) and the Simplexa Flu A/B & RSV (Simplexa). A total of 236 respiratory specimens from patients referred for respiratory viruses testing were retrospectively evaluated; 53 specimens tested positive for each of Flu A, Flu B, and RSV, and 77 specimens tested negative based on the results of the reference method, i.e. the Seegene Allplex Respiratory Panel 1/2/3 (Seegene, Seoul, Korea). The turnaround time (TAT) was 20 min per specimen for cobas Liat and 78 min per eight specimens for Simplexa. The numbers of invalid results were one (0.4%) in cobas Liat and 10 (4.2%) in Simplexa (p < 0.05). All results were consistent with those of the reference method in cobas Liat. The sensitivity and specificity for Flu A, Flu B and RSV A were 100% with Simplexa. However, the sensitivity for RSV B was 80.0% with Simplexa, which was significantly lower than that of cobas Liat (p < 0.05). Comparison of the cycle threshold (Ct) values for RSV with Simplexa and the reference method showed the correlation as continuous variables (p < 0.001) with a higher propensity for obtaining Ct values with Simplexa, the exception being the six false negative results; their Ct values were more than 30 in the reference method. Cobas Liat showed high sensitivity for the detection of RSV B with rapid TAT, and a good workflow efficiency.

microbiology↗