Prevalence and associated factors of locomotive syndrome in young Japanese adults: a cross-sectional study.

Background: The onset of locomotive syndrome (LS) precedes that of frailty. Therefore, the first step in extending healthy life expectancy is to implement measures against LS in young adults. The aim of this study was to investigate the prevalence of LS and its associated factors in young adults for early detection and prevention of LS.

Identification of a novel enhancer essential for expression in T2 cells and activated ILC2s.

The genome organizer, special AT-rich binding protein-1 (SATB1), functions to globally regulate gene networks during primary T cell development and plays a pivotal role in lineage specification in CD4 helper-, CD8 cytotoxic-, and FOXP3 regulatory-T cell subsets. However, it remains unclear how gene expression is controlled, particularly in effector T cell function. Here, by using a novel reporter mouse strain expressing SATB1-Venus and genome editing, we have identified a -regulatory enhancer, essential for maintaining expression specifically in T2 cells.

The Majority of the Serine/Threonine Phosphorylation Sites in Bcl11b Protein Are Dispensable for the Differentiation of T Cells.

Posttranslational modification, such as phosphorylation, is an important biological event that modulates and diversifies protein function. Bcl11b protein is a zinc-finger transcription factor that plays a crucial role in early T cell development and the segregation of T cell subsets. Bcl11b possesses at least 25 serine/threonine (S/T) residues that can be phosphorylated upon TCR stimulation.

Increased angiotensin II coupled with decreased Adra1a expression enhances cardiac hypertrophy in pregnancy-associated hypertensive mice.

Cardiac hypertrophy is a crucial risk factor for hypertensive disorders during pregnancy, but its progression during pregnancy remains unclear. We previously showed cardiac hypertrophy in a pregnancy-associated hypertensive (PAH) mouse model, in which an increase in angiotensin II (Ang II) levels was induced by human renin and human angiotensinogen, depending on pregnancy conditions. Here, to elucidate the factors involved in the progression of cardiac hypertrophy, we performed a comprehensive analysis of changes in gene expression in the hearts of PAH mice and compared them with those in control mice.

Ezrin Regulates Ca Ionophore-Induced Plasma Membrane Translocation of Aquaporin-5.

Aquaporin-5 (AQP5) is selectively expressed in the apical membrane of exocrine glands, such as salivary, sweat, and submucosal airway glands, and plays important roles in maintaining their secretory functions. Because AQP5 is not regulated by gating, localization on the plasma membrane is important for its water-permeable function. Ezrin is an ezrin-radixin-moesin family protein that serves as a crosslinker between the plasma membrane and actin cytoskeleton network.

C-Terminal Domain of Aquaporin-5 Is Required to Pass Its Protein Quality Control and Ensure Its Trafficking to Plasma Membrane.

Aquaporin-5 (AQP5) is selectively expressed in the apical membrane of exocrine glands, such as salivary, lacrimal, and submucosal glands. It is important for the secretory function of exocrine glands because mice with the knockout of AQP5 exhibit a significant reduction in secretion from these glands. Previous reports indicated that the AQP5 C-terminal domain is crucial for the localization of AQP5 at the plasma membrane, but it remains unclear which motif or amino acid residues in the C-terminal domain are essential for this.

Constitutive CD8 expression drives innate CD8 T-cell differentiation via induction of iNKT2 cells.

Temporal down-regulation of the CD8 co-receptor after receiving positive-selection signals has been proposed to serve as an important determinant to segregate helper versus cytotoxic lineages by generating differences in the duration of TCR signaling between MHC-I and MHC-II selected thymocytes. By contrast, little is known about whether CD8 also modulates TCR signaling engaged by the non-classical MHC-I-like molecule, CD1d, during development of invariant natural killer T (iNKT) cells. Here, we show that constitutive transgenic CD8 expression resulted in enhanced differentiation of innate memory-like CD8 thymocytes in both a cell-intrinsic and cell-extrinsic manner, the latter being accomplished by an increase in the IL-4-producing iNKT2 subset.

Differential Requirement of Enhancers E8 and E8 in Cytotoxic Lineage T Cells and in Intestinal Intraepithelial Lymphocytes.

CD8 expression in T lymphocytes is tightly regulated by the activity of at least six enhancers (E8-E8), however their complex developmental stage-, subset-, and lineage-specific interplays are incompletely understood. Here we analyzed ATAC-seq data on the Immunological Genome Project database and identified a similar developmental regulation of chromatin accessibility of a subregion of E8, designated E8-core, and of E8. Loss of E8-core led to a similar reduction in CD8 expression in naïve CD8 T cells and in IELs as observed in mice, demonstrating that we identified the core enhancer region of E8.

Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene.

An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; S4 requires Runx complex binding to exert its silencer function against the enhancer-mediated Cd4 activation by modulating the epigenetic state of the Cd4 gene. Here we identify a late-acting maturation enhancer. Bcl11b plays essential roles for activation of both the early-acting proximal enhancer and maturation enhancer of Cd4.

Data on the TGFβ response of CD4 T cells in the absence of .

The data presented here are related to the research article entitled "Loss of Eed leads to lineage instability and increased CD8 expression of mouse CD4 T cells upon TGFβ signaling" [1]. The cited research article investigates the molecular mechanism of CD8α upregulation observed in -deficient () CD4 T cells upon activation in the presence of TGFβ. This data report describes the effect of retinoic acid (RA) and/or anti-interferon-gamma (IFNγ) antibody supplementation on up-regulation of CD8α and Foxp3 in CD4 T cells, the effect of dose or timing of TGFβ treatment on CD4 T cell identity of , adding further information regarding the conditions that induces CD8α, and mRNA expression changes of genes encoding polycomb repressive complex 2 (PRC2) subunits by TGFβ treatment.

Requirement for intron structures in activating the locus.

During differentiation of CD4CD8 double-positive (DP) thymocytes into the CD4CD8 single-positive (CD8SP) thymocytes committed to the cytotoxic T cell lineage, transcription is temporally terminated after positive selection and is subsequently reinitiated, a process known as coreceptor reversal. Despite the identification of a transcriptional enhancer in the gene that directs reporter transgene expression specifically in CD8SP thymocytes, the molecular mechanisms controlling reactivation of the gene are not fully understood. Here, we show that, after positive selection, hCD2 reporter expression from the locus, which was generated by insertion of hCD2 cDNA into the first exon of the gene, requires the incorporation of intron sequences into the transcript.

Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors.

Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of the gene, is essential for extrathymic differentiation of T cell progenitors.

Loss of Eed leads to lineage instability and increased CD8 expression of mouse CD4 T cells upon TGFβ signaling.

Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a repressive epigenetic modification catalyzed by polycomb repressive complex 2 (PRC2) that is required for proper cell fate determination as well as cellular function. Numerous studies have been performed to elucidate the role of PRC2 in T-cell differentiation and function; however, its role in the regulation of T-helper (Th) subset differentiation and identity has not been fully explored. Here, we report that Eed, an essential subunit of PRC2, is crucial to maintain the identity of CD4 T cells under TGFβ-induced regulatory T cell (Treg)-polarizing conditions.

Unique N-terminal sequences in two Runx1 isoforms are dispensable for Runx1 function.

Background: The Runt-related transcription factors (Runx) are a family of evolutionarily conserved transcriptional regulators that play multiple roles in the developmental control of various cell types. Among the three mammalian Runx proteins, Runx1 is essential for definitive hematopoiesis and its dysfunction leads to human leukemogenesis. There are two promoters, distal (P1) and proximal (P2), in the Runx1 gene, which produce two Runx1 isoforms with distinct N-terminal amino acid sequences, P1-Runx1 and P2-Runx1.

Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.

T-lineage committed precursor thymocytes are screened by a fate-determination process mediated via T cell receptor (TCR) signals for differentiation into distinct lineages. However, it remains unclear whether any antecedent event is required to couple TCR signals with the transcriptional program governing lineage decisions. Here we show that Bcl11b, known as a T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3, central regulators for the CD4-helper/CD8-cytotoxic lineage choice.

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling.

The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfβ2, one of two RNA splice variants of the gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM stage.

Osteochondritis Dissecans of the Humeral Capitellum in Young Athletes: Comparison Between Baseball Players and Gymnasts.

Background: Osteochondritis dissecans (OCD) lesions are often observed in the humeral capitellum both in young baseball players and gymnasts. It is generally believed that capitellar OCD in baseball players can be seen on an anteroposterior (AP) radiograph with the elbow in 45° of flexion. However, the mechanism of injury seems to be different in baseball players and gymnasts.

Distinct requirement of Runx complexes for TCRβ enhancer activation at distinct developmental stages.

A TCRβ enhancer, known as the Eβ enhancer, plays a critical role in V(D)J recombination and transcription of the Tcrb gene. However, the coordinated action of trans-acting factors in the activation of Eβ during T cell development remains uncharacterized. Here, we characterized the roles of Runx complexes in the regulation of the Eβ function.

Epigenetic Thpok silencing limits the time window to choose CD4(+) helper-lineage fate in the thymus.

CD4(+) helper and CD8(+) cytotoxic T cells differentiate from common precursors in the thymus after T-cell receptor (TCR)-mediated selection. Commitment to the helper lineage depends on persistent TCR signals and expression of the ThPOK transcription factor, whereas a ThPOK cis-regulatory element, ThPOK silencer, represses Thpok gene expression during commitment to the cytotoxic lineage. Here, we show that silencer-mediated alterations of chromatin structures in cytotoxic-lineage thymocytes establish a repressive state that is epigenetically inherited in peripheral CD8(+) T cells even after removal of the silencer.

Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes.

TCRαβ thymocytes differentiate into either CD8αβ(+) cytotoxic T lymphocytes or CD4(+) helper T cells. This functional dichotomy is controlled by key transcription factors, including the helper T cell master regulator ThPOK, which suppresses the cytolytic program in major histocompatibility complex (MHC) class II-restricted CD4(+) thymocytes. ThPOK continues to repress genes of the CD8 lineage in mature CD4(+) T cells, even as they differentiate into effector helper T cell subsets.

Cutting edge: fine-tuning of Thpok gene activation by an enhancer in close proximity to its own silencer.

Differentiation of MHC class II-selected thymocytes toward the CD4(+) helper lineage depends on function of the transcription factor ThPOK, whose expression is repressed in CD8(+) cytotoxic lineage cells by a transcriptional silencer activity within the distal regulatory element (DRE) in the Thpok gene. Interestingly, the DRE also functions as a transcriptional enhancer. However, how the DRE exerts such dual functionality remains obscure.

Identification and analysis of an early diagnostic marker for malignant melanoma: ZAR1 intra-genic differential methylation.

Background: Epigenetic changes such as aberrant DNA methylation and histone modification have been shown to play an important role in the tumorigenesis of malignant melanoma.

Objective: To identify novel tumor-specific differentially methylated regions (DMRs) in human malignant melanoma.

Methods: The aberrant methylation at 14 candidate human genomic regions identified through a mouse model study with quantitative DNA methylation analysis using the Sequenom MassARRAY system was performed.