BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis

Regulation of BubR1 is central to the control of APC/C activity. We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass spectrometry and acetylated BubR1-specific antibodies, we have confirmed that BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was required for checkpoint function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was noted that the pre-anaphase degradation was regulated by BubR1 acetylation. Degradation of an acetylation-mimetic form, BubR1–K250Q, was inhibited and chromosome segregation in cells expressing BubR1–K250Q was markedly delayed. By contrast, the acetylation-deficient mutant, BubR1–K250R, was unstable, and mitosis was accelerated in BubR1–K250R-expressing cells. Furthermore, we found that APC/C–Cdc20 was responsible for BubR1 degradation during mitosis. On the basis of our collective results, we propose that the acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing

Prevalence and Risk Factors of Early-Stage Age-Related Macular Degeneration in Patients Examined at a Health Promotion Center in Korea

We evaluated the prevalence and risk factors for early age-related macular degeneration (AMD) in Koreans 50 yr of age or older who were examined at a single health promotion center. We retrospectively reviewed the records of 10,449 subjects who visited the center over a 6-month period. Fundus photography was performed on all subjects, and systematic risk factor analysis was conducted using a structured questionnaire. All patients (n = 322) were initially diagnosed with drusen or early AMD using fundoscopy; the control group (n = 10,127) were those yielding normal fundoscopy findings. The age- and gender-adjusted prevalence of early AMD was 3.08%. Advanced age, male gender, smoking status, hyperlipidemia, working outdoors, and residence in rural areas were all significantly associated with an increased risk for development of early AMD. Higher-level ingestion of fruit or herbal medication and an increased amount of exercise were associated with a lower risk of early AMD development. In our Korean cohort, consisting principally of relatively healthy, middle-class urban adults, the prevalence of early AMD was 3.08% that is similar to that reported in earlier epidemiological studies. Several modifiable risk factors such as smoking and hyperlipidemia are associated with the prevalence of early AMD in our cohort

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity

Background/Aims To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. Methods This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. Results Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. Conclusions In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD

Change in the diagnosis of inflammatory bowel disease: a hospital-based cohort study from Korea

Background/AimsAccurately diagnosing inflammatory bowel disease (IBD) remains a challenge, but is crucial for providing proper management for affected patients. The aim of the present study was to evaluate the frequency of change in diagnosis in Korean patients who were referred to our institution with a diagnosis of IBD.MethodsWe enrolled 1,444 patients diagnosed with ulcerative colitis (UC) and 1,452 diagnosed with Crohn's disease (CD), who had been referred to the Asan Medical Center between January 2010 and December 2014. These patients were assessed and subsequently classified as having UC, CD, indeterminate colitis, possible IBD, or non-IBD.ResultsDuring a median follow-up of 15.9 months, 400 of the 2,896 patients (13.8%) analyzed in this study experienced a change in diagnosis. A change in diagnosis from UC to CD, or vice-versa, was made in 24 of 1,444 patients (1.7%) and 23 of 1,452 patients (1.6%), respectively. A change to a non-IBD diagnosis was the most common modification; 7.5% (108 of 1444) and 12.7% (184 of 1452) of the patients with a referral diagnosis of UC and CD, respectively, were reclassified as having non-IBD. Among the 292 patients who were ultimately determined not to have IBD, 135 (55 UC and 80 CD cases) had received IBD-related medication.ConclusionsThere are diagnostic uncertainties and difficulties in relation to IBD. Therefore, precise assessment and systematic follow-up are essential in the management of this condition

Digital Tourism and Wellbeing: Conceptual Framework to Examine Technology Effects of Online Travel Media

The current pandemic is accelerating the wide-spreading popularity of digital tourism. Given that technology innovation has broadened the horizon of tourist experiences to the realm of virtual environments, this study aims to (re)conceptualize travel experience and develop a theoretical framework to examine media technology effects on virtual travel experience, destination image, and tourists&rsquo; well-being. As a conceptual work, this study adopts technological perspectives on online travel media to decompose technology attributes and articulate distinctive effects of technology-centric variables. The proposed framework illustrates five propositions that specify and explain the relationships among technology-centric variables (modality, agency, interactivity, and navigability), three groups of moderators (user-centric, content-centric, and situation-centric variables), virtual travel experience, destination image, and psychological wellbeing. By adopting the variable-centered approach to decompose online travel media, this study provides a new theoretical lens to understand the psychological mechanism of media technology effects in digital tourism. The framework will serve as useful methodological guidelines to conduct experiments to investigate the distinctive effect of a particular affordance or a specific technical feature. The potential benefits of digital tourism to enhance tourists&rsquo; wellbeing are discussed by highlighting the environmentally friendly and inclusive aspects

Machine learning-based high-frequency neuronal spike reconstruction from low-frequency and low-sampling-rate recordings

&lt;p&gt;Supplementary Data for&lt;strong&gt; "Machine learning-based high-frequency neuronal spike reconstruction from low-frequency and low-sampling-rate recordings", Hong et al.&lt;/strong&gt;&lt;/p&gt

Plant-Expressed Receptor Binding Domain of the SARS-CoV-2 Spike Protein Elicits Humoral Immunity in Mice

The current 15-month coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has accounted for 3.77 million deaths and enormous worldwide social and economic losses. A high volume of vaccine production is urgently required to eliminate COVID-19. Inexpensive and robust production platforms will improve the distribution of vaccines to resource-limited countries. Plant species offer such platforms, particularly through the production of recombinant proteins to serve as immunogens. To achieve this goal, here we expressed the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein in the glycoengineered-tobacco plant Nicotiana benthamiana to provide a candidate subunit vaccine. This recombinant RBD elicited humoral immunity in mice via induction of highly neutralizing antibodies. These findings provide a strong foundation to further advance the development of plant-expressed RBD antigens for use as an effective, safe, and inexpensive SARS-CoV-2 vaccine. Moreover, our study further highlights the utility of plant species for vaccine development