Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking.

promotes zygotic genome activation upon loss of .

Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, -knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here, we present multiple lines of evidence that the multicopy homeobox gene, , encodes a transcription factor that is highly expressed in mouse two-cell embryos and redundantly drives ZGA.

Relationship between Serum Concentrations and Muscular Expressions of Selenoproteins on Selenium-Supplemented Insulin Resistance Mouse Model.

Previously, insulin resistance and hepatic oxidative stress with increased expressions of glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were induced in NSY mice, a diabetic mouse model, by administrating a high fat diet (HFD) and seleno-L-methionine (SeMet) for 12 weeks. In this study we developed an analysis method for serum selenoproteins using LC-tandem mass spectrometry (LC-MS/MS) and investigated the effects of supplementary selenium on serum concentrations of selenoproteins as well as protein expression in skeletal muscle as a major insulin target tissue under the same experimental condition. The glucose area under the curves for oral glucose tolerance and insulin tolerance tests indicated that the HFD induced insulin resistance, whereas the treatment of SeMet + HFD showed insignificant promotion compared with the HFD-induced insulin resistance.

Establishment of Reference Reagents for Single-Radial-Immunodiffusion Assay on the 2022/23 Seasonal Influenza Vaccine in Japan and Their Quality Validation.

Potency tests for influenza vaccines are currently performed using a single-radial immunodiffusion (SRID) assay, which requires a reference antigen and anti-hemagglutinin (HA) serum as reference reagents. Reagents must be newly prepared each time a strain used for vaccine production is modified. Therefore, establishing reference reagents of consistent quality is crucial for conducting vaccine potency tests accurately and precisely.

Investigation of HO uptake mechanisms onto multiple-component ambient aerosols collected in summer and winter time in Yokohama, Japan.

The heterogeneous loss of HO radicals onto ambient aerosols plays an important role in tropospheric chemistry. However, sparse investigation of the dominating parameters controlling the HO uptake coefficients onto ambient aerosols (γHO) has largely hindered the application of the measured γHO to the global spatial prediction. Here we induced an offline method using LFP-LIF technique to measure the kinetics of HO uptake onto ambient aerosols collected in summertime and wintertime in Yokohama city, a regional urban site near Tokyo, Japan.

Transcription of MERVL retrotransposons is required for preimplantation embryo development.

Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive.

Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant.

Although the immunological memory produced by BNT162b2 vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been well studied and established, further information using different racial cohorts is necessary to understand the overall immunological response to vaccination. We evaluated memory B and T cell responses to the severe acute respiratory syndrome coronavirus 2 spike protein before and after the third booster using a Japanese cohort. Although the Ab titer against the spike receptor-binding domain (RBD) decreased significantly 8 mo after the second vaccination, the number of memory B cells continued to increase, whereas the number of memory T cells decreased slowly.

TDP-43 safeguards the embryo genome from L1 retrotransposition.

Transposable elements (TEs) are genomic parasites that propagate within the host genome and introduce mutations. Long interspersed nuclear element-1 (LINE-1 or L1) is the major TE class, which occupies nearly 20% of the mouse genome. L1 is highly active in mammalian preimplantation embryos, posing a major threat to genome integrity, but the mechanism of stage-specific protection against L1 retrotransposition is unknown.

Nationwide and long-term molecular epidemiologic studies of mumps viruses that circulated in Japan between 1986 and 2017.

In Japan, major mumps outbreaks still occur every 4-5 years because of low mumps vaccine coverage (30-40%) owing to the voluntary immunization program. Herein, to prepare for a regular immunization program, we aimed to reveal the nationwide and long-term molecular epidemiological trends of the mumps virus (MuV) in Japan. Additionally, we performed whole-genome sequencing (WGS) using next-generation sequencing to assess results from conventional genotyping using MuV sequences of the small-hydrophobic (SH) gene.

Potential Factors Contributing to Ozone Production in AQUAS-Kyoto Campaign in Summer 2020: Natural Source-Related Missing OH Reactivity and Heterogeneous HO/RO Loss.

This study presents total OH reactivity, ancillary trace species, HO reactivity, and complex isoprene-derived RO reactivity due to ambient aerosols measured during the air quality study (AQUAS)-Kyoto campaign in September, 2020. Observations were conducted during the coronavirus disease (COVID-19) pandemic (associated with reduced anthropogenic emissions). The spatial distribution of missing OH reactivity highlights that the origin of volatile organic compounds (VOCs) may be from natural-emission areas.

Personal Exposure to Fine Particles (PM) in Northwest Africa: Case of the Urban City of Bamako in Mali.

Personal exposure to particulate matter (PM) from anthropogenic activities is a major concern in African countries, including Mali. However, knowledge of particulates is scant. This study was undertaken to characterize personal exposure to PM microns or less in diameter (PM) in the city of Bamako in Mali.

Antiviral Activity of CD437 Against Mumps Virus.

Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral candidates. In this study, we evaluated a screening method using an green fluorescent protein-expressing MuV infectious molecular clone.

The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost their lives.

Naturally Oxidized Olive Oil Promotes Active Cutaneous Anaphylaxis and Th2 Cytokine Production.

The excessive ingestion of oxidized dietary oils may exacerbate some allergic diseases. We previously reported that oxidized olive oil exacerbates active cutaneous anaphylaxis (ACA), one of the immediate allergic reactions. This study was conducted to clarify the effects of oxidized olive oil on the T cell response during ACA.

Potent mouse monoclonal antibodies that block SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a global pandemic since its first outbreak in the winter of 2019. An extensive investigation of SARS-CoV-2 is critical for disease control. Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis.

Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells.

Piwi associates with PIWI-interacting RNAs (piRNAs) and represses transposons transcriptionally through heterochromatinization; however, this process is poorly understood. Here, we identify Brahma (Brm), the core adenosine triphosphatase of the SWI/SNF chromatin remodeling complex, as a new Piwi interactor, and show Brm involvement in activating transcription of Piwi-targeted transposons before silencing. Bioinformatic analyses indicated that Piwi, once bound to target RNAs, reduced the occupancies of SWI/SNF and RNA polymerase II (Pol II) on target loci, abrogating transcription.

Total hydroxyl radical reactivity measurements in a suburban area during AQUAS-Tsukuba campaign in summer 2017.

Missing hydroxyl radical (OH) reactivity from unknown/unmeasured trace species empirically accounts for 10%-30% of total OH reactivity and may cause significant uncertainty regarding estimation of photochemical ozone production. Thus, it is essential to unveil the missing OH reactivity for developing an effective ozone mitigation strategy. In this study, we conducted simultaneous observations of total OH reactivity and 54 reactive trace species in a suburban area as part of the Air QUAlity Study (AQUAS)-Tsukuba campaign for the summer of 2017 to gain in-depth insight into total OH reactivity in an area that experienced relatively high contributions of secondary pollutants.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

Objectives: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated.

Methods: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC.

Results: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells.

Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming.

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome.

Relative and Absolute Sensitivity Analysis on Ozone Production in Tsukuba, a City in Japan.

The change in the ozone production rate on reducing its precursors, namely, ozone production sensitivity, is important information for developing a strategy to reduce ozone. We expanded a conventional sensitivity analysis theory by including peroxy radical loss by uptake onto particle surfaces in the aim of examining their potential impact. We also propose a new concept of absolute sensitivity that enables us to evaluate the quantitative effectiveness of precursor reduction toward mitigating ozone production over a given period and area.

Essential roles of Windei and nuclear monoubiquitination of Eggless/SETDB1 in transposon silencing.

Eggless/SETDB1 (Egg), the only essential histone methyltransferase (HMT) in Drosophila, plays a role in gene repression, including piRNA-mediated transposon silencing in the ovaries. Previous studies suggested that Egg is post-translationally modified and showed that Windei (Wde) regulates Egg nuclear localization through protein-protein interaction. Monoubiquitination of mammalian SETDB1 is necessary for the HMT activity.

Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing.

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15.

Seroprevalence of mumps before the introduction of mumps-containing vaccine in Lao PDR: results from a nationwide cross-sectional population-based survey.

Objective: Mumps-containing vaccine is currently not a component of the national immunization schedule in Lao People's Democratic Republic (PDR). Mumps itself is not a notifiable disease in the country and the seroprevalence of anti-mumps immunoglobulin G (IgG) in the general population is unknown. In this study, anti-mumps IgG was measured in 2058 blood samples to evaluate population immunity in the country.

Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification.

The mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is enriched in the paraxial mesoderm and is implicated in somite formation, but its function in other mesoderms remains elusive. Here, using direct reprogramming-based screening, single-cell RNA-seq in mouse embryos, and directed cardiac differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6 induces nascent mesoderm from PSCs and determines cardiovascular and somite lineage specification via its temporal expression.