Centromeric histone H3, CENP-A^Cse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-A^Cse4restricts its localization to centromeres. Mislocalization of CENP-A^Cse4is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro. Ubiquitination of Cse4 by the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal physiological conditions. Accumulation of sumoylated Cse4 species and increased stability of Cse4 in slx5∆ strains suggest that sumoylation precedes ubiquitin-mediated proteolysis of Cse4. Slx5-mediated Cse4 proteolysis is independent of Psh1, since slx5∆ psh1∆ strains exhibit higher levels of Cse4 stability and mislocalization than either slx5∆ or psh1∆ strains. Our results demonstrate a role for Slx5 in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain genome stability.

The individual prevalence of sleep-disordered breathing (SDB), short sleep duration, and obesity is high and increasing. The study aimed to investigate potential associations between SDB, objective sleep duration, obesity, diabetes and hypertension across genders, and the effect of pre- or post-menopausal status. A cross-sectional study evaluated 7051 community participants with wrist actigraphy for a week, and nocturnal oximetry ≥ 2 nights. SDB was assessed by 3 per cent oxygen desaturation index (ODI) corrected for sleep duration obtained from wrist actigraphy. Moderate-to-severe SDB was defined as ODI3% levels ≥ 15 per hour. Both logODI3% and body mass index showed independent negative associations with sleep duration (β = −0.16, p < 0.001 and β = −0.07, p < 0.001, respectively). Moderate-to-severe SDB (men/premenopausal women/postmenopausal women; 23.7/1.5/9.5%, respectively) was associated with a higher risk of diabetes in premenopausal women (OR 28.1; 95%CI 6.35–124.6; p < 0.001) and postmenopausal women (OR 3.25; 95%CI 1.94–5.46; p < 0.001), but not in men (OR 1.47; 95%CI 0.90–2.40; p = 0.119). Moderate-to-severe SDB was associated with a higher risk of hypertension in men (OR 3.11; 95%CI 2.23–4.33; p < 0.001), premenopausal women (OR 3.88; 95%CI 1.42–10.6; p = 0.008), and postmenopausal women (OR 1.96; 95%CI 1.46–2.63; p < 0.001). Short sleep duration was not associated with diabetes or hypertension. The associations of obesity with diabetes or hypertension were indirectly mediated by SDB (24.0% and 21.5%, respectively), with possible sex differences emerging (men/women; 15.3/27.8% and 27.0/16.9%, respectively). Notwithstanding the cross-sectional design, SDB and obesity, but not short sleep duration, were independently associated with diabetes and hypertension, with gender and menopausal status–related differences in risk emerging.

Background: In an aging society, worsening chronic diseases increase the burden on patients and the health care system. Using online health information including health information via social networking sites (SNSs), such as Facebook and YouTube, may play an important role in the self-management of chronic diseases and health promotion for internet users. Objective: This study aims to improve strategies for promoting access to reliable information for the self-management of chronic diseases via the internet, and to identify populations facing barriers to using the internet for health, we examined chronic diseases and characteristics associated with online health information seeking and the use of SNSs. Methods: This study used data from the INFORM Study 2020, which was a nationally representative cross-sectional postal mail survey conducted using a self-administered questionnaire in 2020. The dependent variables were online health information seeking and SNS use. Online health information seeking was assessed using 1 question about whether respondents used the internet to find health or medical information. SNS use was assessed by inquiring about the following 4 aspects: visiting SNSs, sharing health information on SNSs, writing in an online diary or blog, and watching a health-related video on YouTube. The independent variables were 8 chronic diseases. Other independent variables were sex, age, education status, work, marital status, household income, health literacy, and self-reported health status. We conducted a multivariable logistic regression model adjusted for all independent variables to examine the associations of chronic diseases and other variables with online health information seeking and SNS use. Results: The final sample for analysis comprised 2481 internet users. Hypertension or high blood pressure, chronic lung diseases, depression or anxiety disorder, and cancer were reported by 24.5%, 10.1%, 7.7%, and 7.2% of respondents, respectively. The odds ratio of online health information seeking among respondents with cancer was 2.19 (95% CI 1.47-3.27) compared with that among those without cancer, and the odds ratio among those with depression or anxiety disorder was 2.27 (95% CI 1.46-3.53) compared with that among those without. Further, the odds ratio for watching a health-related YouTube video among those with chronic lung diseases was 1.42 (95% CI 1.05-1.93) compared with that among those without these diseases. Women, younger age, higher level of education, and high health literacy were positively associated with online health information seeking and SNS use. Conclusions: For patients with cancer, strategies for promoting access to websites with reliable cancer-related information as well as access among patients with chronic lung diseases to YouTube videos providing reliable information may be beneficial for the management of these diseases. Moreover, it is important to improve the online environment to encourage men, older adults, internet users with lower education levels, and those with low health literacy to access online health information.

Background: During the COVID-19 pandemic, much misinformation and disinformation emerged and spread rapidly via the internet, posing a severe public health challenge. While the need for eHealth literacy (eHL) has been emphasized, few studies have compared the difficulties involved in seeking and using COVID-19 information between adult internet users with low or high eHL. Objective: This study examines the association between eHL and web-based health information–seeking behaviors among adult Japanese internet users. Moreover, this study qualitatively shed light on the difficulties encountered in seeking and using this information and examined its relationship with eHL. Methods: This cross-sectional internet-based survey (October 2021) collected data from 6000 adult internet users who were equally divided into sample groups by gender, age, and income. We used the Japanese version of the eHL Scale (eHEALS). We also used a Digital Health Literacy Instrument (DHLI) adapted to the COVID-19 pandemic to assess eHL after we translated it to Japanese. Web-based health information–seeking behaviors were assessed by using a 10-item list of web sources and evaluating 10 topics participants searched for regarding COVID-19. Sociodemographic and other factors (eg, health-related behavior) were selected as covariates. Furthermore, we qualitatively explored the difficulties in information seeking and using. The descriptive contents of the responses regarding difficulties in seeking and using COVID-19 information were analyzed using an inductive qualitative content analysis approach. Results: Participants with high eHEALS and DHLI scores on information searching, adding self-generated information, evaluating reliability, determining relevance, and operational skills were more likely to use all web sources of information about COVID-19 than those with low scores. However, there were negative associations between navigation skills and privacy protection scores when using several information sources, such as YouTube (Google LLC), to search for COVID-19 information. While half of the participants reported no difficulty seeking and using COVID-19 information, participants who reported any difficulties, including information discernment, incomprehensible information, information overload, and disinformation, had lower DHLI score. Participants expressed significant concerns regarding “information quality and credibility,” “abundance and shortage of relevant information,” “public trust and skepticism,” and “credibility of COVID-19–related information.” Additionally, they disclosed more specific concerns, including “privacy and security concerns,” “information retrieval challenges,” “anxieties and panic,” and “movement restriction.” Conclusions: Although Japanese internet users with higher eHEALS and total DHLI scores were more actively using various web sources for COVID-19 information, those with high navigation skills and privacy protection used web-based information about COVID-19 cautiously compared with those with lower proficiency. The study also highlighted an increased need for information discernment when using social networking sites in the “Health 2.0” era. The identified categories and themes from the qualitative content analysis, such as “information quality and credibility,” suggest a framework for addressing the myriad challenges anticipated in future infodemics.