Effect of Display Position During Treadmill Exercise

Department of Biomedical EngineeringTreadmill walking or running is a common daily exercise that can be easily carried out at public gyms as well as private home. In general, indoor treadmill walking and running are performed while watching video contents through a display, which is mounted around the control panel of the treadmill or on a stand at about eye height in front of the treadmill. It is assumed that the two different positions of the display would induce different head and neck postures when conducting treadmill exercises, and it may affect the muscular loads on the neck or back musculature. However, there is a lack of information on how the position of the display affects the user???s walking and running posture and the muscular load on the upper body. Therefore, this study was conducted to determine the effect of display position on postures and muscular loads during walking and running on a treadmill. This study quantitatively evaluated the effect of the display position on the cervical and lumbar spine musculoskeletal system. Seventeen participants performed walking and running in two display position conditions: a standing monitor located in front of the participant's gaze and a monitor located on the treadmill control panel. The kinematic variables of the lower extremities and spatiotemporal gait parameters were quantified using a three-dimensional motion capture system. Electromyography sensors for assessing muscular loads were attached to the neck, shoulder, and lower back muscles. The activation level of muscles, kinematics variables, and gait parameters were compared between two display position conditions by the one-way repeated measures ANOVA. The results of this study showed that the neck flexion angle and the activation level of neck extensor muscles under the panel display condition was significantly greater during both walking and running except for the 10th percentile level of muscle activation in running task (p<0.05). The head vertical acceleration value was significantly higher under the front display condition during running (p<0.05). There was no significant difference in trunk flexion, but the activation level of erector spinae muscles was higher under the panel display condition (p<0.05). During running, the trunk flexion was significantly higher under the panel display condition (p<0.05), the activation level of erector spinae muscles had no significant difference between the conditions. The findings of this study provide evidence that watching video on a display mounted on the treadmill while walking or running can pose larger biomechanical stress on the neck musculature compared to the eye-level display position in front of the treadmill. Considering the frequency and duration of daily treadmill exercises, such a display position should be avoided to reduce potential risks for neck musculoskeletal problems.ope

Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia

Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia.111Ysciescopu

Deficiency of Capicua disrupts bile acid homeostasis

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type 1 and cancer in mammals; however, the in vivo physiological functions of CIC remain largely unknown. Here we show that Cic hypomorphic (Cic-L-/-) mice have impaired bile acid (BA) homeostasis associated with induction of proinflammatory cytokines. We discovered that several drug metabolism and BA transporter genes were down-regulated in Cic-L-/- liver, and that BA was increased in the liver and serum whereas bile was decreased within the gallbladder of Cic-L-/- mice. We also found that levels of proinflammatory cytokine genes were up-regulated in Cic-L-/- liver. Consistent with this finding, levels of hepatic transcriptional regulators, such as hepatic nuclear factor 1 alpha (HNF1 alpha), CCAAT/enhancer-binding protein beta (C/EBP beta), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXR alpha), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (Tnf alpha) expression and decrease in the levels of FOXA2, C/EBP beta, and RXRa were found in Cic-L-/- liver before BA was accumulated, suggesting that inflammation might be the cause for the cholestasis in Cic-L-/- mice. Our findings indicate that CIC is a critical regulator of BA homeostasis, and that its dysfunction might be associated with chronic liver disease and metabolic disorders.1

다중오믹스 분석법 기반 아목시실린/클라불란산 유발 인체 간손상 생체지표 탐색

학위논문 (박사)-- 서울대학교 대학원 : 협동과정임상약리학전공, 2017. 2. 조주연.Introduction: Drug-induced liver injury (DILI) is a major challenge in the development and use of therapeutic drugs. The exploration for more sensitive biomarkers of DILI requires multidirectional approaches. However, a comprehensive clinical study has not been conducted in healthy volunteers. To explore potential biomarkers for and mechanisms of amoxicillin/clavulanate-induced liver injury (AC-DILI), we conducted a clinical trial based on multi-omics approaches. Methods: Thirty-two healthy Korean male volunteers were enrolled and grouped according to 4 GSTT1/M1 genotypes (8 subjects per group). Blood and urine samples were collected before and after 14 days of amoxicillin/clavulanic acid administration for liver function tests and quantification of biomarkers. The approaches used throughout this study included a liver function test, pharmacokinetic analysis, microRNA quantification, pharmacometabolomics analysis, human leukocyte antigen (HLA) typing, and lymphocyte transformation test (LTT). We evaluated the correlations between liver function parameters and multi-omics biomarkers. Results: Comparative analyses between Responder and Non-Responder groups classified by the alanine aminotransferase (ALT) elevation level revealed no statistically significant differences in primary pharmacokinetic (PK) parameters of amoxicillin or clavulanate. Liver-specific microRNA-122 (miR-122) was highly correlated with ALT. Urinary metabolites, including 7-methylxanthine, 7-methyluric acid, 3-methylxanthine, and azelaic acid, showed significantly different levels between the two groups (P<0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC-DILI, including metabolic changes, increased miR-122 level, increased liver enzyme activity and enhanced lymphocyte proliferation after drug administration. Conclusion: This is the first study to evaluate potential AC-DILI biomarkers in healthy volunteers. The results confirm miR-122 and four urinary metabolites as early and sensitive biomarkers for AC-DILI, suggesting hepatocellular injury, liver inflammation, and mitochondrial oxidative stress as mechanisms underlying AC-DILI. Proliferation of lymphocytes in response to the drug also suggests a role for the adaptive immune response in AC-DILI. The biomarkers evaluated in this study by integrating omics data could enable more sensitive and earlier prediction of liver injury in drug development and usage of therapeutics.1 INTRODUCTION 1 2 MATERIALS AND METHODS 6 2.1 Study Subjects 6 2.2 Study Design 7 2.3 Ethical Consideration 10 2.4 Quantification of the amoxicillin/clavulanate concentrations 13 2.5 PK Analyses 15 2.6 GSTT1/GSTM1 and HLA typing 16 2.7 Measurement of serum miRNAs 17 2.8 Pharmacometabolomic analyses 20 2.9 Lymphocyte transformation test (LTT) 21 2.10 Statistical analysis 22 3 RESULTS 23 3.1 Demographics 23 3.2 Group classification 25 3.3 Correlation of PK parameters with ALT elevations 32 3.4 Correlation between miR-122 and ALT elevation 36 3.5 Localization of miR-122 43 3.6 Pharmacometabolomic analyses 44 3.7 Lymphocyte proliferation against amoxicillin and clavulanate 53 3.8 HLA genotyping 54 4 DISCUSSION 57 5 CONCLUSION 63 6 References 64 7 국문초록 71Docto

Center of Pressure Trajectory and Spatiotemporal Gait Parameters When Walking with Limited Knee Flexion

Stiff-knee, which indicates reduced range of knee flexion, may decrease gait stability. Although it is closely related to an increase in fall risk, the effect of limited knee flexion on the balance capacity during walking has not been well studied. This study aimed at examining how walking with limited knee flexion would influence the center of pressure (COP) trajectory and spatiotemporal gait parameters. Sixteen healthy young participants conducted four different walking conditions: normal walking and walking with limited knee flexion of their left knee up to 40 and 20 degrees, respectively. Results show that the participants walked significantly (p&amp;lt;0.05) slower with shorter stride length, wider step width, less cadence, and decreased stance phase when walking with limited knee flexion, compared to normal walking. The increase in the asymmetry and variability of the COP was also observed. It indicates that limited knee flexion during walking might affect the dynamic balance

A biosensor for the detection of single base mismatches in microRNA

Graphene oxide quenches fluorescence corresponding to only a mismatched target due to selective denaturing of the thermo-unstable duplex composed of probe peptide nucleic acid and single base mismatched target RNA and thus, the fluorescence signal only from perfectly matched target RNA is measured. This journal is © The Royal Society of Chemistry 2015114141sciescopu