dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes

dREAM complexes represent the predominant form of E2F/RBF repressor complexes in Drosophila. dREAM associates with thousands of sites in the fly genome but its mechanism of action is unknown. To understand the genomic context in which dREAM acts we examined the distribution and localization of Drosophila E2F and dREAM proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM sites and binding sites for the insulator-binding proteins CP190 and Beaf-32. Genetic assays show that these components functionally co-operate and chromatin immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is important for association of CP190 with chromatin. dE2F2/dREAM binding sites are enriched at divergently transcribed genes, and the majority of genes upregulated by dE2F2 depletion represent the repressed half of a differentially expressed, divergently transcribed pair of genes. Analysis of mutant animals confirms that dREAM and CP190 are similarly required for transcriptional integrity at these gene pairs and suggest that dREAM functions in concert with CP190 to establish boundaries between repressed/activated genes. Consistent with the idea that dREAM co-operates with insulator-binding proteins, genomic regions bound by dREAM possess enhancer-blocking activity that depends on multiple dREAM components. These findings suggest that dREAM functions in the organization of transcriptional domains

Risk factors for deaths associated with COVID-19 according to the cause of death classification in Republic of Korea

Objectives This study aimed to classify coronavirus disease 2019 (COVID-19)-related deaths according to whether COVID-19 was listed as the cause of death, and to investigate the differences in demographic characteristics and risk factors for COVID-19 death classifications. Methods A total of 5,625 deaths in South Korea among patients with confirmed COVID-19 from January 20, 2020 to December 31, 2021 were selected. Excluding false reports and unnatural deaths, 5,597 deaths were analyzed. Based on death report data, deaths were classified according to whether the cause of death was listed as COVID-19 (CD) or not (NCD). The epidemiological characteristics and causes of deaths were investigated using descriptive, univariate, and multivariate statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to analyze the risk factors. Results The case fatality ratio was 0.89% and increased with age. Additionally, 96.4% of the subjects had an underlying disease, and 53.4% died in winter. The proportion of NCDs was 9.3%, of whom 19.1% died at home and 39.0% were confirmed to have COVID-19 after death. Malignant neoplasms (102/416 vs. 637/4,442; OR, 1.71; 95% CI, 1.36−2.16; p<0.001) were significantly associated with NCD. Conclusion This is the first study to analyze risk factors by cause of death using COVID-19 death report data in South Korea. These results are expected to be used as evidence for establishing a death monitoring system that can collect timely information in a new infectious disease pandemic

Changes in the intrinsic severity of severe acute respiratory syndrome coronavirus 2 according to the emerging variant: a nationwide study from February 2020 to June 2022, including comparison with vaccinated populations

Background As the population acquires immunity through vaccination and natural infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the intrinsic severity of coronavirus disease (COVID-19) is becoming challenging. We aimed to evaluate the intrinsic severity regarding circulating variants of SARS-CoV-2 and to compare this between vaccinated and unvaccinated individuals. Methods With unvaccinated and initially infected confirmed cases of COVID-19, we estimated the case severity rate (CSR); case fatality rate (CFR); and mortality rate (MR), including severe/critical cases and deaths, stratified by age and compared by vaccination status according to the period regarding the variants of COVID-19 and vaccination. The overall rate was directly standardized with age. Results The age-standardized CSRs (aCSRs) of the unvaccinated group were 2.12%, 5.51%, and 0.94% in the pre-delta, delta, and omicron period, respectively, and the age-standardized CFRs (aCFRs) were 0.60%, 2.49%, and 0.63% in each period, respectively. The complete vaccination group had lower severity than the unvaccinated group over the entire period showing under 1% for the aCSR and 0.5% for the aCFR. The age-standardized MR of the unvaccinated group was 448 per million people per month people in the omicron period, which was 11 times higher than that of the vaccinated group. In terms of age groups, the CSR and CFR sharply increased with age from the 60 s and showed lower risk reduction in the 80 s when the period changed to the omicron period. Conclusions The intrinsic severity of COVID-19 was the highest in the delta period, with over 5% for the aCSR, whereas the completely vaccinated group maintained below 1%. This implies that when the population is vaccinated, the impact of COVID-19 will be limited, even if a new mutation appears. Moreover, considering the decreasing intrinsic severity, the response to COVID-19 should prioritize older individuals at a higher risk of severe disease

Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53

The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE)

Abstract Backgrounds Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887

Examining the role of integration experiences in shaping immigrants’ post-migration food choices and eating practices in Ontario, Canada

Despite the extensive literature on immigrants’ post-migration dietary transitions and their implications for long-term health and well-being, little research has been conducted to link these processes to their integration experiences. This dissertation contributes to the current literature by examining the interrelationship between immigrants’ integration experiences – especially their economic integration – and their post-migration food choices and eating practices. The first integrated article (Chapter 2) draws on qualitative interviews with 38 recent immigrants in two Ontario cities (Toronto and London) in Canada. First, this chapter focuses on illustrating recent immigrants’ general experiences in managing their post-migration food choices and eating practices in Canada. Second, this chapter further explores what structural aspects related to immigrants’ integration experiences play a role in shaping their opportunities and barriers to healthy eating. The next integrated article (Chapter 3) draws on qualitative interviews with 23 immigrant men and immigrant women that are heterosexually married. This chapter takes an intersectional life course approach to explore who takes on the responsibility of “feeding the family” and identifies forces and pressures that encourage taking on such a role. Further, I also examine what specific challenges these immigrant families experience and what strategies they adopt as they endeavour to produce healthy, home-cooked meals. The last integrated article (Chapter 4) is a case study using a mixed-method approach. By analyzing quantitative data from the 2015 Canadian Community Health Survey, this study first examines the awareness and usage of Canada’s Food Guide among Canadian adults in Ontario, comparing how immigrants differ from native-born Canadians. Second, I draw on qualitative data from 45 in-depth interviews with recent immigrants and international students to further explore their general experiences in accessing and using Canada’s Food Guide. The overarching goal of this dissertation is to contribute to the current literature on immigrant integration, lifestyle, health, and well-being – and also to suggest future directions for policies surrounding immigration and their health and well-being

Factors Influencing Intention to Use Mobility as a Service: Case Study of Gyeonggi Province, Korea

Mobility as a service (MaaS) integrates various transportation modalities and connects these modalities to enable users to travel from departure points to destination points. The objectives of this study were to analyze the factors influencing the intention to use MaaS and determine a direction for the implementation of this service. Hence, this study utilized an ordered probit model and marginal effect analysis. Specifically, a survey was conducted based on citizens living in Gyeonggi-do, South Korea, to prepare logical MaaS operation measures customized in this province. Subsequently, variables related to MaaS were classified, and statistical analysis was performed based on these variables. The need for integrated transportation service, intention to use shared mobility, gender, household income, and region are found to have significant effects. Moreover, demographic groups with high levels of intention to use MaaS were identified. Finally, the intention to use MaaS was found to be mainly affected by whether public transportation was the primary means of transportation or whether the subjects spent a comparatively long time commuting. It is expected that these findings will serve as the basis for MaaS implementation in the future and will also be used as fundamental data for transportation service planning

A case of gemcitabine-induced thrombotic microangiopathy in a urothelial tumor patient with a single kidney

Thrombotic microangiopathy (TMA) is a rare complication of gemcitabine treatment. A 55-year-old man with a history of urothelial cancer underwent right ureteronephrectomy and palliative chemotherapy. The patient presented with dyspnea, generalized edema with foamy urine, and new-onset hypertension with acute kidney injury (AKI). Although AKI with oliguria was evident, thrombocytopenia and hemolytic anemia were not overt. To determine the cause of rapidly progressive azotemia, kidney biopsy was performed despite a single kidney and revealed chronic TMA. Microangiopathic hemolytic anemia and thrombocytopenia developed after renal biopsy. Diagnosed as gemcitabine-induced TMA, gemcitabine cessation and active treatment including steroids, plasmapheresis, and rituximab were carried out, but the patient׳s condition progressed to a dialysis-dependent state. Gemcitabine-induced TMA is often difficult to diagnose because of its variable clinical course. Therefore, heightened awareness of this potentially lethal complication of gemcitabine is essential; renal biopsy may be helpful

Profiling the polyadenylated transcriptome of extracellular vesicles with long-read nanopore sequencing

Abstract Background While numerous studies have described the transcriptomes of extracellular vesicles (EVs) in different cellular contexts, these efforts have typically relied on sequencing methods requiring RNA fragmentation, which limits interpretations on the integrity and isoform diversity of EV-targeted RNA populations. It has been assumed that mRNA signatures in EVs are likely to be fragmentation products of the cellular mRNA material, and the extent to which full-length mRNAs are present within EVs remains to be clarified. Results Using long-read nanopore RNA sequencing, we sought to characterize the full-length polyadenylated (poly-A) transcriptome of EVs released by human chronic myelogenous leukemia K562 cells. We detected 443 and 280 RNAs that were respectively enriched or depleted in EVs. EV-enriched poly-A transcripts consist of a variety of biotypes, including mRNAs, long non-coding RNAs, and pseudogenes. Our analysis revealed that 10.58% of all EV reads, and 18.67% of all cellular (WC) reads, corresponded to known full-length transcripts, with mRNAs representing the largest biotype for each group (EV = 58.13%, WC = 43.93%). We also observed that for many well-represented coding and non-coding genes, diverse full-length transcript isoforms were present in EV specimens, and these isoforms were reflective-of but often in different ratio compared to cellular samples. Conclusion This work provides novel insights into the compositional diversity of poly-A transcript isoforms enriched within EVs, while also underscoring the potential usefulness of nanopore sequencing to interrogate secreted RNA transcriptomes

Histone modification in Saccharomyces cerevisiae: A review of the current status

The budding yeast Saccharomyces cerevisiae is a well-characterized and popular model system for investigating histone modifications and the inheritance of chromatin states. The data obtained from this model organism have provided essential and critical information for understanding the complexity of epigenetic interactions and regulation in eukaryotes. Recent advances in biotechnology have facilitated the detection and quantitation of protein post-translational modification (PTM), including acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, and acylation, and led to the identification of several novel modification sites in histones. Determining the cellular function of these new histone markers is essential for understanding epigenetic mechanisms and their impact on various biological processes. In this review, we describe recent advances and current views on histone modifications and their effects on chromatin dynamics in S. cerevisiae