56016 research outputs found
Sort by
Explainable Deep Supervised Leaning-based Biological Age Estimation with Risk Score
Get PDFDepartment of Industrial EngineeringThe pursuit of immortality and longevity without illness has been a longstanding aspiration of humanity. Since the accurate assessment and management of individuals' current health status is a fundamental step in achieving human wellness, the advancements of health indices remain ongoing endeavors. Recently, several machine learning or deep learning methods have been proposed to estimate biological age (BA) by predicting chronological age or extracting latent representations of health data. However, most previous studies cannot reflect disease information, one of the most important health risk factors, and have also been deficient in clarifying the variable???s importance for BA estimation. Therefore, in this study, we propose a deep supervised learning-based BA estimation method with an explainable autoencoder by reflecting both individuals??? health risk status and disease prevalence to extract latent embeddings. To be specific, we present a self-one-to-one correspondence layer with a Lasso loss function adopted for autoencoder architecture to enhance the model???s interpretability. In addition, we use a supervised loss to predict disease incidence as well as reconstruction loss of the autoencoder to comprehensively represent both a person???s health data and its transformed information with respect to risk. We believe that the proposed method offers a useful solution for improving the explainability and accuracy of BA estimation and contributes to leading personalized health management.clos
Dynamics of nuclear proteostasis network upon cellular stress
No full textDepartment of Biological Sciencesclos
Deciphering the Molecular Mechanisms of Orai1-dependent Entosis in Cancer Development and SEPTINs Cleavage-mediated Ciliary Defects in Coronavirus Infection
Get PDFDepartment of Biological SciencesThe cytoskeleton is a complex network of protein filaments that plays a crucial role in maintaining cell shape, organizing cellular components, and coordinating various cellular processes. This study aimed to explore the regulation of the cytoskeleton in the context of cancer development and investigate the mechanism underlying cytoskeletal defects during virus infection. It provides insights into the pathogenesis of various disease and identify potential therapeutic targets.
In the first part, I described the regulation mechanism of cytoskeleton during cancer development, specifically in the context of Entosis. Entosis is a non-apoptotic cell death process that forms characteristic cell-in-cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca2+ and Ca2+ channels participating in entosis are unclear. Here, I showed that intracellular Ca2+ signaling regulates entosis via SEPTIN-Orai1-Ca2+/CaM-MLCK-actomyosin axis. Intracellular Ca2+ oscillations in entotic cells showed spatiotemporal variations during engulfment, mediated by Orai1 Ca2+ channels in plasma membranes. SEPTIN controlled polarized distribution of Orai1 for local MLCK activation, resulting in MLC phosphorylation and actomyosin contraction, leading to internalization of invasive cells. Ca2+ chelators and SEPTIN, Orai1, and MLCK inhibitors suppressed entosis. This study identified potential targets for treating entosis-associated tumors, showed that Orai1 is an entotic Ca2+ channel that provides essential Ca2+ signaling, and shed light on the molecular mechanism underlying entosis that involves SEPTIN filaments, Orai1, and MLCK.
In the second part, I explored the mechanism underlying cytoskeletal defects during virus infection, focusing on their implications in ciliopathy. Coronaviruses target ciliate cells causing the loss of cilia, acute rhinorrheas, and other ciliopathies. The loss of ciliary function may help the virus infect, replicate, and spread. However, the molecular mechanisms by which coronaviruses cause ciliary defects are still unclear. Herein I demonstrate how coronavirus infection and SARS-CoV-2 3CL protease induce cilia dysfunction by targeting a host protein septin that is required for the structure and function of cilia. Further, I demonstrate that coronaviruses and 3CL protease lead to the cleavage of several septin proteins (SEPT2, 6, and 9), producing cleaved obstructive fragments. Furthermore, ectopic expression of cleaved SEPT2 fragments shows defective ciliogenesis, disoriented septin filaments, and ablated Sonic Hedgehog (SHH) signaling in a protease activity-dependent manner. I present that the 3CLpro inhibitors are potent and prevent abnormal ciliary structures and SHH signaling. These results provide useful insights into the general mechanisms underlying ciliary defects caused by coronaviruses, which in turn facilitate virus spread and prove that preclinical and clinical 3CL protease inhibitors may prove useful as therapeutics for treating ciliary defects of coronaviruses.clos
Mechanistic Insights for Mitoguardin-2 Mediated Lipid Transport at ER-Mitochondria Contact Site Based on Crystal Structure
No full textDepartment of Biological SciencesEukaryotic cells have various types of subcellular compartments called organelles. For cell survival and maintenance of their function, organelles communicate with each other. In the past, the only known method of organelle communication was through vesicle trafficking. Recently, with the development of electron microscopy techniques, it has been discovered that cellular organelles also make contact sites known as membrane contact sites (MCS). MCSs are maintained stably by tethering structures mainly composed of proteins. MCSs are important sites for cellular processes such as molecule trafficking, inheritance, intracellular signaling, and organelle dynamics. The endoplasmic reticulum (ER) ???mitochondrial contact sites (ERMCS) have multiple functional processes, such as exchanging biomolecules like Ca2+ and lipids, signaling ions and lipids, regulating membrane dynamics, and apoptosis. In particular, phospholipid trafficking between the ER and mitochondria is crucial for phospholipid metabolism. Mitoguardin-2 (MIGA2) forms ERMCS with VAPB, an ER membrane protein, in higher eukaryotic cells. Therefore, MIGA2 regulates de novo lipogenesis with VAPB in adipocytes. Here, we show two crystal structures of the MIGA2 and the MIGA2-VAPB complex. We determined the MIGA2 lipid droplet (LD)-targeting domain and the MIGA2 phospho-FFAT motifVAPB complex structure at resolutions of 2.85 ?? and 1.68 ??, respectively. The LD-targeting domain comprises 11 ?? helices and has a large hydrophobic cavity containing phospholipids. A positively charged concave surface, composed of ??7 and ??8 helices of the LD-targeting domain, mediates docking on the organelle membrane surface. MIGA2 has lipid transport activity via its large hydrophobic cavity, and it preferentially transfers phosphatidylserine (PS). The MIGA2 FFAT motif has serine residues substituted for glutamate or aspartate residues. Phosphorylation of these two serine residues allows for complex formation with VAPB, leading to the formation of ERMCS. After ERMCS formation, MIGA2 transfers phospholipids between the ER and mitochondria.
Next, Vacuolar protein 8 (Vac8), a vacuolar protein of Saccharomyces cerevisiae, is known to mediate various cellular processes through interactions with binding partners. Vac8 forms a complex with Nvj1 to create the nuclear-vacuole junction (NVJ), and with Atg13 to mediate the cytoplasm-to-vacuole targeting (Cvt) pathway. Additionally, Vac8 associates with Myo2 through its interaction with Vacuolar protein 17 (Vac17) for vacuolar inheritance. Here, we solve the crystal structure of the Vac8-Vac17 complex at a 2.1 ?? resolution. Vac8 binds to Vac17 in an antiparallel manner. The extended loop of Vac17 binds to the conserved inner groove of Vac8 armadillo repeats. In the structure, the Vac17 HN2 helix interacts with the Vac8 H1 helix, which differs from the binding mode seen in other Vac8 complex structures. Due to the capture of Vac8 H1 helix by Vac17 HN helix, Vac8 does not form homodimers when binding to Vac17.clos
Control of Proton Tunneling in Interfacial Water Network with Cooperative Motion
No full textDepartment of Materials Science and Engineeringclos
MOCVD??? ???????????? ?????? (111)?????? ????????? ????????? ?????? ????????? ???????????? ??????????????????????????? ??????
No full textDepartment of Materials Science and Engineeringclos
Autonomous electrolyte formulation using robotics and Bayesian optimization
No full textSchool of Energy and Chemical Engineering (Energy Engineering (Battery Science and Technology))clos
Enhanced Deep Anomaly Detection In Contaminated Datasets Using Semi-Supervised Learning
No full textGraduate School of Artificial Intelligenceclos
?????? ?????? ??????????????? ??????-??????????????? ????????? ?????? ????????? ?????? ?????? ?????? ??????
No full textDepartment of Chemistryclos
Constructing High-Performance Ternary Device Using Analogous Polymer Donors
No full textBoth ternary copolymerization and ternary blending are effective methods to fine-tune polymer structure and manipulate thin-film morphology to improve device performance. In this work, three D-A-A-A (D: donor, A: acceptor) terpolymer donors (FY1, FY2, and FY3) are synthesized by introducing BDD (1,3-bis(2-ethylhexyl)-5,7-di(thiophen-2-yl)benzo[1,2-c:4,5-c']dithiophene-4,8-dione) units into the D-A alternating copolymer PM6 backbone. Owing to the promoted conjugated planarity and excellent absorption of BDD, the obtained terpolymers display an extended absorption range and enhanced (p-p) stacking orientation, which is a promising third component in ternary device. As a result, the optimal FY1:PM6:BTP-eC9-based ternary device afforded an impressive power conversion efficiency (PCE) as high as 18.52%, owing to the efficient charge transport, negligible energy loss, and suitable domain size. The result provides an efficient method to obtain high-performance polymer solar cells by using analogous polymer donors in ternary device