MOLECULAR MECHANISM OF HUMAN MISMATCH REPAIR INITIATION

DNA mismatch repair (MMR) is a highly conserved pathway that maintains genomic stability primarily by correcting mismatches generated during DNA replication. MMR deficiency leads to microsatellite instability (MSI), which is a hallmark of HNPCC (Hereditary Nonpolyposis Colorectal Cancer). Human mismatch repair is initiated by MutSα, a heterodimer of MSH2 and MSH6 subunits. Mismatch binding by MutSα triggers a series of downstream MMR events including interacting and communicating with other MMR proteins. The ATPase domain of MutSα is situated in the C-termini of its both subunits, and ATP binding is required for dissociation of MutSα from a mismatch. In eukaryotic cells, a strand break, which resides either 3’ or 5’ to the mismatch up to several hundred base pair away, determines the strand specificity of MMR. However, in spite of extensive studies, the mechanism by which MutSα locates and senses a nick from the mismatch, and coordinates the subsequent steps of MMR remains poorly understood. Two controversial models have been proposed to explain how the mismatch and the strand break communicate each other. Sliding model proposes that MutSα slides along the DNA helix from the mismatch to the strand break in an ATP binding-dependent but not ATP hydrolysis-dependent manner. Stationary model postulates that MutSα remains bound at the mismatch, and a protein-mediated DNA loop forms, physically bringing the mismatch and the nick in contact. Here, we tested these models in vitro, using a circular plasmid DNA substrate with a single GT mismatch and two Lac repressor (Lac I) binding sites as conditional physical \u27roadblocks\u27, one on either side of the mismatch, which when present, prevent MutSα from sliding bi-directionally along the DNA. The results showed that DNA excision initiates under conditions that block MutSα sliding, suggesting that initiation of excision is independent of whether MutSα slides from the mismatch to the nick. This result implies that the communication between the mismatch and the nick is likely through interactions between the mismatch-bound MutSα and other MMR components at the strand break, supporting the stationary model. Therefore, these studies provide significant insight into the mechanisms of mismatch correction in human cells

Magnetic activity variability of nearby bright Sun-like stars by 4-year intensive Hα\alpha line monitoring

We report intensive monitoring of the activity variability in the H$\alpha$ line for 10 Sun-like stars using the 1.88-m reflector at Okayama Branch Office, Subaru Telescope, during the last four years 2019-2022. Our aim was to investigate features of the stellar magnetic activity behaviors. We correlated the H$\alpha$ line variability of each star with the stellar activity levels derived from the Ca II H&K line, suggesting its efficiency as a magnetic activity indicator. In analyzing the H$\alpha$ line variation, we observed that some stars exhibited linear or quadratic trends during the observation period. Among several G- and K-type stars expected to have co-existing activity cycles, we confirmed the 2.9-yr short cycle of $\epsilon$ Eri (K2V) from the H$\alpha$ observations. Additionally, we established upper limits on the H$\alpha$ variability of $\beta$ Com (G0V) and $\kappa$$^1$ Cet (G5V) concerning their expected shorter cycles. We also detected the possibility of short-term activity cycles in two F-type stars, $\beta$ Vir (F9V; $\sim$ 530 days) and $\alpha$ CMi (F5IV-V; $\sim$ 130 days). The cycle in $\alpha$ CMi was observed in only one season of our 4-yr observations, suggesting the temporal absence of the cycle period. However, for stars with planets, we did not observe significant magnetic activity variability likely associated with the planetary orbital period. It is speculated that the impact of H$\alpha$ variability on radial velocity (RV) measurements may vary with spectral type.Comment: 27 pages, 12 figures, Accepted by PAS

Magnetic activity variability from Hα\alpha line intensive monitoring for two F-type stars having a hot-Jupiter, τ\tau Bootis A and υ\upsilon Andromedae A

We report the results of intensive monitoring of the variability in the H$\alpha$ line for two F-type stars, $\tau$ Boo and $\upsilon$ And, during the last four years 2019-2022, in order to investigate their stellar magnetic activity. The 4-year H$\alpha$ line intensity data taken with the 1.88-m reflector at Okayama Branch Office, Subaru Telescope, shows the existence of a possible $\sim$ 123-day magnetic activity cycle of $\tau$ Boo. The result of the H$\alpha$ variability as another tracer of the magnetic activity on the chromosphere is consistent with previous studies of the Ca II H&K line and suggests that the magnetic activity cycle is persisted in $\tau$ Boo. For $\upsilon$ And, we suggest a quadratic long-term trend in the H$\alpha$ variability. Meanwhile, the short-term monitoring shows no significant period corresponding to specific variations likely induced by their hot-Jupiter in both cases ($\approx$ 3.31 and 4.62 days, respectively). In this H$\alpha$ observation, we could not find any signature of the Star-Planet Magnetic Interaction. It is speculated that the detected magnetic activity variability of the two F-type stars is related to the stellar intrinsic dynamo.Comment: 27 pages, 20 figures, 1 table, Accepted by Publications of the Astronomical Society of Japa

Detecting Depression of Cancer Patients with Daily Mental Health Logs from Mobile Applications

Mobile mental health trackers, the mobile applications that gather self-reported mental logs from users, have gained recent attention from clinicians as a tool for detecting patients’ depression. However, critics have raised questions about the validity of the data collected from mental health trackers, which ask only a few simple questions using the face emoticon scale. This is the first study to address this issue, and we provide theoretical discussion that leads to the following hypotheses: (1) simpler but larger datasets collected daily from mobile mental health trackers can serve as good indicators to detect patients’ depression, and (2) higher adherence to mobile mental health trackers enhances screening accuracy. We test our hypotheses using the dataset of 5,792 sets of daily mental health logs collected from 78 breast cancer patients. Our random logistic panel regression and ROC analysis results, as well as k-means clustering analysis, provide strong supports for both hypotheses

Dynamics of Social Influence on New Employees’ Use of Volitional IS: m-EHR Case in Hospital Setting

It is widely recognized that user resistance to Information Systems (IS) is particularly high in hospitals. In this regard, the future of mobile Electronic Health Record (m-EHR) systems is highly in question, mainly because their usage is not mandatory. Aiming to provide insights on how best to promote the use of m-EHR in hospitals, we investigate the effect of social influences on m-EHR usage by new doctors who recently began working at a hospital. Drawing upon the concept of organizational socialization and social influences, we hypothesize that coworkers’ m-EHR usage is positively associated with one by new doctors, and the strength of this association varies by the coworkers’ type of usage, by the hierarchical rankings of coworkers, and by the stage of socialization process in which the new doctors are situated. Our analyses using longitudinal m-EHR usage data (595,914 logs of 737 doctors) generally support our hypotheses

Motivations for self-archiving on an academic social networking site:A study on researchgate

© 2019 ASIS & T This study investigates motivations for self-archiving research items on academic social networking sites (ASNSs). A model of these motivations was developed based on two existing motivation models: motivation for self-archiving in academia and motivations for information sharing in social media. The proposed model is composed of 18 factors drawn from personal, social, professional, and external contexts, including enjoyment, personal/professional gain, reputation, learning, self-efficacy, altruism, reciprocity, trust, community interest, social engagement, publicity, accessibility, self-archiving culture, influence of external actors, credibility, system stability, copyright concerns, additional time, and effort. Two hundred and twenty-six ResearchGate users participated in the survey. Accessibility was the most highly rated factor, followed by altruism, reciprocity, trust, self-efficacy, reputation, publicity, and others. Personal, social, and professional factors were also highly rated, while external factors were rated relatively low. Motivations were correlated with one another, demonstrating that RG motivations for self-archiving could increase or decrease based on several factors in combination with motivations from the personal, social, professional, and external contexts. We believe the findings from this study can increase our understanding of users' motivations in sharing their research and provide useful implications for the development and improvement of ASNS services, thereby attracting more active users

Novel involvement of leukotriene B4 receptor 2 through ERK activation by PP2A down-regulation in leukotriene B4-induced keratin phosphorylation and reorganization of pancreatic cancer cells

AbstractPerinuclear reorganization via phosphorylation of specific serine residues in keratin is involved in the deformability of metastatic cancer cells. The level of leukotriene B4 is high in pancreatic cancers. However, the roles of LTB4 and its cognate receptors in keratin reorganization of pancreatic cancers are not known. LTB4 dose-dependently induced phosphorylation and reorganization of Keratin 8 (K8) and these processes were reversed by LY255283 (BLT2 antagonist). BLT2 agonists such as Comp A and 15(S)-HETE also induced phosphorylation of serine 431 in K8. Moreover, Comp A-induced K8 phosphorylation and reorganization were blocked by LY255283. Gene silencing of BLT2 suppressed Comp A-induced K8 phosphorylation and reorganization in PANC-1 cells. Over-expression of BLT2 promoted K8 phosphorylation. Comp A promoted the migration of PANC-1 cells in a dose-dependent manner, and LY255283 blocked Comp A-induced migration, respectively. PD98059 (ERK inhibitor) suppressed Comp A-induced phosphorylation of serine 431 and reorganization of K8. Gene silencing of BLT2 suppressed the expression of pERK, and over-expression of BLT2 increased the expression of pERK even without Comp A. Comp A induced the expression of active ERK (pERK) and BLT2. These inductions were blocked by PD98059. Comp A decreased PP2A expression and hindered the binding of PP2A to the K8, leading to the activation of ERK. PD98059 suppressed the Comp A-induced migration of PANC-1 cells and BLT2 over-expression-induced migration of PANC-1 cells. Overall, these results suggest that BLT2 is involved in LTB4‐induced phosphorylation and reorganization through ERK activation by PP2A downregulation, leading to increased migration of PANC‐1 cells