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2. Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells

Author

Lee, Eunsang, Kim, Donghee, Song, Yo Han, Shin, Kyujin, Song, Sanggeun, Lee, Minho, Goh, Yeongchang, Lim, Mi Hee, Kim, Ji-Hyun, Sung, Jaeyoung, and Lee, Kang Taek

Subjects
Physics - Biological Physics
Abstract

Synaptic vesicle transport by motor proteins along microtubules is a crucial active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM's active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor-protein-multiplexes have both static and dynamic motility fluctuations. The loss of the fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.

Published
2024
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7. Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)

Author

Lim, Sung Hee, Lee, Keun-Wook, Kim, Jae-Joon, Im, Hyeon-Su, Kim, In-Ho, Han, Hye Sook, Koo, Dong-Hoe, Cho, Jang Ho, Maeng, Chi Hoon, Lee, Min-Young, Lee, Hyo Jin, Kim, Jwa Hoon, Park, Sang Gon, Jung, Joo Young, Shin, Seong-Hoon, Kim, Ki Hyang, Kim, Hyeyeong, Oh, So Yeon, Kang, Minsu, Jung, Minkyu, and Rha, Sun Young

Published
2024
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9. Real-Time Tracking of Vesicles in Living Cells Reveals That Tau-Hyperphosphorylation Suppresses Unidirectional Transport by Motor Proteins

Author

Lee, Eunsang, Kim, Donghee, Song, Yo Han, Shin, Kyujin, Song, Sanggeun, Lee, Minho, Goh, Yeongchang, Lim, Mi Hee, Kim, Ji-Hyun, Sung, Jaeyoung, and Lee, Kang Taek

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurodegenerative, Dementia, Neurosciences, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Acquired Cognitive Impairment, Underpinning research, 1.1 Normal biological development and functioning, Neurological
Abstract

Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from those of VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM’s active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor protein multiplexes have both static and dynamic motility fluctuations. The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.

Published
2024

14. Role of Dual-Acquisition Noninvasive Cardiac CT Imaging for the Detection of Vasospastic Angina.

Author

Jin, Xuan, Kang, Eun-Ju, Jin, Cai-De, Lee, Kwang-Min, Lim, Kyung-Hee, Rha, Seung-Woon, Choi, Cheol-Ung, Yong, Hwan-Seok, Yun, Sung-Cheol, Budoff, Matthew J, Yu, Long-Hao, and Kim, Moo-Hyun

Subjects
computed tomography angiography, coronary vasospasm, positive predictive value, specificity, Atherosclerosis, Heart Disease - Coronary Heart Disease, Clinical Research, Cardiovascular, Heart Disease, Biomedical Imaging, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Clinical Sciences
Abstract

BackgroundVasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method.MethodsWe prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (

Published
2023

21. Long-term exposure to ambient air pollution and risk of lung cancer – A comparative analysis of incidence and mortality in four administrative cohorts in the ELAPSE study

Author

Chen, Jie, Atkinson, Richard W., Andersen, Zorana Jovanovic, Oftedal, Bente, Stafoggia, Massimo, Lim, Youn-Hee, Bekkevold, Terese, Krog, Norun Hjertager, Renzi, Matteo, Zhang, Jiawei, Bauwelinck, Mariska, Janssen, Nicole, Strak, Maciek, Forastiere, Francesco, de Hoogh, Kees, Rodopoulou, Sophia, Katsouyanni, Klea, Raaschou-Nielsen, Ole, Samoli, Evangelia, Brunekreef, Bert, Hoek, Gerard, and Vienneau, Danielle

Published
2024
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28. Residential exposure to transportation noise and risk of incident atrial fibrillation: a pooled study of 11 prospective Nordic cohorts

Author

Thacher, Jesse D., Roswall, Nina, Ögren, Mikael, Pyko, Andrei, Åkesson, Agneta, Oudin, Anna, Rosengren, Annika, Poulsen, Aslak H., Eriksson, Charlotta, Segersson, David, Rizzuto, Debora, Helte, Emilie, Andersson, Eva M., Aasvang, Gunn Marit, Engström, Gunnar, Gudjonsdottir, Hrafnhildur, Selander, Jenny, Christensen, Jesper H., Brandt, Jørgen, Leander, Karin, Overvad, Kim, Mattisson, Kristoffer, Eneroth, Kristina, Stucki, Lara, Barregard, Lars, Stockfelt, Leo, Albin, Maria, Simonsen, Mette K., Raaschou-Nielsen, Ole, Jousilahti, Pekka, Tiittanen, Pekka, Ljungman, Petter L.S., Jensen, Steen S., Gustafsson, Susanna, Yli-Tuomi, Tarja, Cole-Hunter, Thomas, Lanki, Timo, Lim, Youn-Hee, Andersen, Zorana J., Pershagen, Göran, and Sørensen, Mette

Published
2024
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39. Spatial and Temporal Variation of Façade-Level Particle Number Concentrations Using Portable Monitors in Copenhagen, Denmark

Author

Bergmann, Marie L, Taghavi Shahri, Seyed Mahmood, Tayebi, Shali, Kerckhoffs, Jules, Cole-Hunter, Thomas, Hoek, Gerard, Lim, Youn-Hee, Massling, Andreas, Vermeulen, Roel, Loft, Steffen, Andersen, Zorana J, Amini, Heresh, Bergmann, Marie L, Taghavi Shahri, Seyed Mahmood, Tayebi, Shali, Kerckhoffs, Jules, Cole-Hunter, Thomas, Hoek, Gerard, Lim, Youn-Hee, Massling, Andreas, Vermeulen, Roel, Loft, Steffen, Andersen, Zorana J, and Amini, Heresh

Abstract

Ultrafine particles (UFP), commonly expressed as particle number concentrations (PNC), have been associated with harm to human health yet are currently not regulated or routinely monitored in many places. This has limited the potential for studies of health effects of long-term exposure to UFP. The present study aims to understand the spatial and temporal variation in façade-level UFP exposures in Copenhagen, Denmark. We measured PNC at the façades of 27 residences across the city for approximately 72 h each in two campaigns and continuously at an urban background reference site for twelve consecutive months, using portable monitors (miniature diffusion size classifiers [DiSCminis]). We estimated annual means at the residential sites based on temporal adjustment using reference site data. Furthermore, we co-located the DiSCminis at a regulatory monitoring station on three occasions and compared daily means from our reference site to those from seven fixed-site monitoring stations throughout the city. Annual mean PNC at the reference site was 4,715 (SD of hourly mean: 3,001) pt/cm 3, while annual means at 27 residences were slightly higher with a mean of 5,201 pt/cm 3 (SD: 807), ranging between 3,735 and 6,588 pt/cm 3. The two individual adjusted campaign-specific means at 27 residential sites were weakly correlated (Spearman's correlation 0.11) and had an intra-class correlation coefficient of 0.06 (95%-confidence interval: -0.18, 0.28). Daily PNC at the reference site was highly correlated (R=0.64-0.84) with PNC monitored at seven fixed-site stations throughout the city. We observed a seasonal trend at the reference site with the highest PNC in spring. Our measurement campaign revealed that façade-level PNC at residences in Copenhagen in 2021-2022 were relatively low with small spatial variability. The large variability in time suggests possibly longer and more frequent measurement campaigns to obtain more stable annual averages. Our study illustrates the challe

Published
2025

40. Long-term exposure to green and blue space and incidence of cardiovascular disease:A Danish Nurse Cohort study

Author

Li, Yujing, Zhang, Jiawei, Schipperijn, Jasper, Tuffier, Stéphane, Hyman, Samuel, Bergmann, Marie, Ketzel, Matthias, Backalarz, Claus, Andersen, Zorana Jovanovic, Lim, Youn Hee, Cole-Hunter, Thomas, Li, Yujing, Zhang, Jiawei, Schipperijn, Jasper, Tuffier, Stéphane, Hyman, Samuel, Bergmann, Marie, Ketzel, Matthias, Backalarz, Claus, Andersen, Zorana Jovanovic, Lim, Youn Hee, and Cole-Hunter, Thomas

Abstract

Background: Few cohort studies have examined the associations of natural surroundings (green and blue space) with cardiovascular disease (CVD) and show mixed findings. We aimed to investigate the associations between long-term exposure to green and blue space and incidence of CVD in the Danish Nurse Cohort. Methods: We followed 19,070 female nurses living in Denmark from 1993/1999 to 2018. The shortest Euclidian distance from a residence to three types of green space (park, woodland, and heathland) and four types of blue space (lake, river, coast, and wetland), along with total count of all types of natural surroundings within a 500 meter (m), 1000 m, and 5000 m radius from a residence, were calculated using GeoDanmark data from 2005. Distance was log-transformed to correct for a right-skewed data distribution. Residential air pollution and road traffic noise data for 2005 were estimated by the Danish air pollution modeling system (‘DEHM/UBM/AirGIS’) and Nord2000 model, respectively. Cox proportional hazards models were used to estimate associations between green and blue space and the first-ever incidence of total CVD and certain CVD subtypes after adjusting for individual factors, air pollution, and noise. We examined effect modification by age, smoking status, occupational status, household income, and urbanicity level. Hazard ratio (HR) and 95% confidence interval (95% CI) were presented per e unit (equivalent to ∼2.72 fold) increase in distance. Results: 8179 new cases of CVD were observed over 344,084 person-years. Living further from woodland was associated with higher stroke incidence (HR: 1.153; 95% CI: 1.029–1.293), while living further from heathland was associated with reduced total CVD incidence (HR: 0.975; 95% CI: 0.955–0.996). No associations were found between distance to park, woodland, lake, river, coast, or wetland and total CVD incidence. Total count of all types of green and blue spaces within a 5000 m radius was linked to a reduced risk of C

Published
2025

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