Changes in work and life patterns associated with depressive symptoms during the COVID-19 pandemic: an observational study of health app (CALO mama) users

BACKGROUND: During the COVID-19 pandemic, many people refrained from going out, started working from home (WFH), and suspended work or lost their jobs. This study examines how such pandemic-related changes in work and life patterns were associated with depressive symptoms. METHODS: An online survey among participants who use a health app called CALO mama was conducted from 30 April to 8 May 2020 in Japan. Participants consisted of 2846 users (1150 men (mean age=50.3) and 1696 women (mean age=43.0)) who were working prior to the government declaration of a state of emergency (7 April 2020). Their daily steps from 1 January to 13 May 2020 recorded by an accelerometer in their mobile devices were linked to their responses. Depressive symptoms were assessed using the Two-Question Screen. RESULTS: On average, participants took 1143.8 (95% CI -1557.3 to -730.2) fewer weekday steps during the declaration period (from 7 April to 13 May). Depressive symptoms were positively associated with female gender (OR=1.58, 95% CI 1.34 to 1.87), decreased weekday steps (OR=1.22, 95% CI 1.03 to 1.45) and increased working hours (OR=1.73, 95% CI 1.32 to 2.26). Conversely, starting WFH was negatively associated with depressive symptoms (OR=0.83, 95% CI 0.69 to 0.99). CONCLUSIONS: Decreased weekday steps during the declaration period were associated with increased odds of depressive symptoms, but WFH may mitigate the risk in the short term. Further studies on the longitudinal effects of WFH on health are needed

Working from home and dietary changes during the COVID-19 pandemic: A longitudinal study of health app (CALO mama) users

It is plausible that the coronavirus disease pandemic and related changes in work and life patterns affected dietary patterns, but existing studies have limitations owing to a cross-sectional design. Using longitudinal data, we examined dietary changes in people due to the pandemic and work and life patterns. We conducted an online survey on changes in work and life patterns during the pandemic from April 30, 2020, to May 8, 2020, among users of a health app called CALO mama provided in Japan. We retrieved and linked the dietary data for 5929 participants from January 1, 2020, to May 13, 2020. Generalized linear mixed models were used to estimate the frequencies of food intake associated with the pandemic and work and life patterns. During the state of emergency, the frequency of intake of vegetables, beans, seaweeds, fish, meats, dairy products, and snacks increased, whereas alcohol intake decreased. Working from home was associated with increased intake of vegetables, fruits, dairy products, and snacks but decreased intake of seaweeds, meats, and alcohol. Time spent on childcare was associated with decreased intake of vegetables and fruits but increased intake of meats. Probable depressive symptoms were negatively associated with the frequency of food intake other than snacks and alcohol. We conclude that diet quality improved during the pandemic in general, but attention must be paid to overconsumption of snacks and negative factors such as increased burden of childcare and depression for healthy eating

Ethanol-induced Stress Leads to Apoptosls Via Endoplasmic Reticulum Stress in SK-Hepl Cells

Alcoholic liver disease causes oxidative stress and induces apoptosis during alcohol metabolism. Ethanol causes endoplasmic reticulum (ER) stress in hepatocytes, stimulating the unfolded protein response (UPR) pathway and/or Ca2+-dependent calpain and caspase-4 activities. However, it is poorly understood whether ethanol-induced oxidative stress directly leads to apoptosis promoted by ER stress-associated pathways. This study investigated this question in human liver adenocarcinoma (SK-Hep1) cells, which were treated with 200 mM ethanol for 5 hours in the presence or absence of the antioxidant N-acetyl-cysteine (NAC). We found that treatment with ethanol significantly increased ROS production and cellular apoptosis in the SK-Hep1 cells, and that this response was significantly suppressed by pretreatment with NAC. Furthermore, pretreatment with NAC significantly reduced the observed increases in the mRNA expressions of Bip, Chop, and sXbp-1, and the activity of caspase-3 in ethanol-induced apoptotic cells. However, pretreatment with NAC did not attenuate the transient rise in cytosolic Ca2+ nor the activities of caspase-4 and calpain induced by ethanol. Together, these results revealed that ethanol-induced stress promotes apoptosis not only through mitochondria-mediated pathways, but also via ER stress. The findings further suggested that ethanol-induced oxidative stress and non-oxidative stress both stimulate the pathway regulating ER stress-mediated apoptosis

The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis

Protein ubiquitination is a post-translational protein modification that regulates many biological conditions [1], [2], [3], [4]. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1 [5], [6]. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12mt/mt) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16 [7], [8], [9], [10]. In contrast, Trip12mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

Apoptosis-induced Proliferation in UV-Irradiated Human Conjunctival Epithelial Cells

A pterygium is a benign growth that develops on the conjunctiva and, in some cases, extends to the cornea and interferes with vision. Excessive exposure to ultraviolet (UV) light is one of the causes of pterygium development. We previously reported that UV-induced apoptosis is led by production of reactive oxygen species (ROS) that activate p38 mitogen-activated protein kinase (MAPK) in human conjunctival epithelial (HCE) cells. Also, ROS-dependent induction of interleukin-11 (IL-11) has been reported to upregulate MAPK pathways, which results in compensatory proliferation. In this study, we examined the effect of UV exposure on HCE cells, in terms of change in apoptosis, ROS generation, phosphorylation of c-Jun N-terminal kinase (JNK), levels of IL-11 (a key cytokine in tissue repair and compensatory proliferation), production of activator protein 1 (AP-1), and expression of c-myc, c-fos and c-jun (which provides evidence of healthy cell proliferation). Apoptosis in HCE cells was induced by UV light irradiation (312nm, 4.94mW/cm2). Apoptosis was measured using the Muse Annexin V and Dead Cell Assay Kit. ROS generation was measured by using 5-(and 6-) chloromethyl-2\u277\u27-dichlorodihydrofluorescein diacetate, acetyl ester. JNK phosphorylation, IL-11 levels and AP-1 production were measured by enzyme-linked immunosorbent assays (ELISAs). Imnunocytochemical staining was used to measure c-myc, c-fos and c-jun expression. UV irradiation increased ROS generation, phosphorylation of JNK, and apoptotic cell count. IL-11 levels and AP-1 production were significantly increased by UV irradiation. The irradiated cells had increased expression of c-myc, c-fos and c-jun, and treatment of the cells with IL-11 significantly increased expression of c-myc, c-fos and c-jun. These results suggest that the release of IL-11 from UV-induced apoptotic HCE cells and surrounding healthy cells could promote proliferation to maintain homeostasis

Abdominal subcutaneous adipose tissue accumulation is positively correlated with hepatic steatosis in Sprague-Dawley rats

The precise roles of visceral (VAT) or subcutaneous adipose tissue (SAT) on hepatic fat accumulation have not been fully elucidated. In this report, we examined the correlation between VAT or SAT volume and severity of hepatic fat accumulation. In the present study, Sprague-Dawley (SD) rats were fed a standard diet containing 10% fat or a high-fat diet containing 45% or 60% fat for 16 weeks. Abdominal VAT and SAT volume, as well as fat percentage of the liver were measured by computed tomography (CT). Hepatic triglyceride (TG) content and histopathological findings of hepatic steatosis were also examined. Abdominal SAT weight/body weight ratio was positively and strongly correlated with abdominal VAT weight/body weight ratio. Fat percentage of the liver by CT evaluation, hepatic TG content, and hepatic steatosis score by histopathological evaluation showed positive correlations with one another. Fat percentage of the liver by CT evaluation and hepatic TG content was positively correlated with both the abdominal VAT weight/body weight ratio and SAT weight/body weight ratio, respectively. Furthermore, hepatic TG content was negatively correlated with the abdominal VAT weight/SAT weight ratio. Our data suggest that abdominal SAT accumulation is positively correlated with hepatic steatosis in SD rats, rather than abdominal VAT accumulation. Further investigations are needed in order to clarify the precise mechanisms of SAT and VAT effects on the development of hepatic fat accumulation

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead