Monoclonal antibody Y01 prevents tauopathy progression induced by lysine 280-acetylated tau in cell and mouse models.

The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide 275VQIINK280 of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies, including AD. However, the mechanism that links tau acetylated on lysine 280 (tau-acK280) to subsequent progression to neurodegenerative disease remains unclear. Here, we demonstrate that tau-acK280 is critical for tau propagation processes including secretion, aggregation, and seeding. We developed an antibody, Y01, that specifically targets tau-acK280 and solved the crystal structure of Y01 in complex with an acK280 peptide. The structure confirmed that Y01 directly recognizes acK280 and the surrounding residues. Strikingly, upon interaction with acetylated tau aggregates, Y01 prevented tauopathy progression and increased neuronal viability in neuron cultures and in tau-Tg mice through antibody-mediated neutralization and phagocytosis, respectively. Based on our observations that tau-acK280 is a core species involved in seeding and propagation activities, the Y01 antibody that specifically recognizes acK280 represents a promising therapeutic candidate for AD and other neurodegenerative diseases associated with tauopathy.

Multiple chemical sensitivity caused by exposure to ignition coal fumes: a case report.

BACKGROUND: Although multiple chemical sensitivity (MCS) is a well-known disorder caused by environmental exposures, MCS caused by occupational exposure has been reported in Korea. Therefore, we report a MCS case caused by environmental exposure to ignition coal after a differential diagnosis to exclude other diseases. CASE REPORT: Since 2011, a 55-year-old woman had experienced edema, myalgia, and other symptoms when she smelled ignition coal near her workplace. She had been diagnosed with fibromyalgia syndrome(FMS) and was treated, with no improvement of symptoms. Since then, she showed the same symptoms after exposure to city gas, the smell of burning, and exhaust gas. To avoid triggering substances, she moved to a new house and used an air purifier. She quit her job in November 2012. After visiting our hospital, she underwent a differential diagnosis for FMS, chronic fatigue syndrome, and somatization disorder. She was diagnosed with MCS by the Korean version of the Quick Environment Exposure Sensitivity Inventory (QEESI). She was educated about the disease and to avoid triggering substances. She received ongoing treatment for her symptoms. CONCLUSION: This case showed that symptoms began after smelling ignition coal. After that, her triggers was increased such as the smell of city gas, burning, and exhaust gas. This case is the first reported in Korea of MCS due to environmental exposure after ruling out other diseases.

Long working hours and emotional well-being in korean manufacturing industry employees.

OBJECTIVES: Korea is well known for its long work hours amongst employees. Because workers of the manufacturing industry are constantly exposed to extended work hours, this study was based on how long work hours affect their emotional well-being. METHODS: The analysis was done using the secondary Korean Working Condition Survey (KWCS). Long work hours were defined to be more than 48 hours, and they were subcategorized into units of 52 hours and 60 hours. Based on the WHO (five) well-being index, emotional state was subdivided into three groups - reference group, low-mood group, and possible depression group- where 28 points and 50 points were division points, and two groups were compared at a time. Association between long work hours and emotional state was analyzed using binary and multinomial logistic regression analysis. RESULTS: Working for extended working hours in the manufacturing industry showed a statistically significant increase (t test p < 0.001) in trend among the possible depression group when compared to the reference group and the low-mood group. When demographical characteristics, health behaviors, socioeconomic state, and work-related characteristics were fixed as controlled variables, as work hours increased the odds ratio of the possible depression group increased compared to the reference group, and especially the odds ratio was 2.73 times increased for work hours between 48-52 and 4.09 times increased for 60 hours or more and both were statistically significant. In comparing the low-mood group and possible depression group, as work hours increased the odds ratio increased to 1.73, 2.39, and 4.16 times, and all work hours from working 48-52 hours, 53-60 hours, and 60 hours or more were statistically significant. Multinomial logistic regression analysis also showed that among the reference group and possible group, the possible depression group was statistically significant as odds ratio increased to 2.94 times in working 53-60 hours, and 4.35 times in 60 hours or more. CONCLUSIONS: Long work hours have an adverse effect on emotional well-being. A more diversified research towards variables that affect long work hours and emotional well-being and how they interact with each other and their relationship to overall health is imperative.