Calmodulin: a highly conserved and ubiquitous Ca sensor.

Calcium ions (Ca) play critical roles in various biological phenomena. The free Ca concentration in the cytoplasm of a resting cell is at the 10 M level, whereas that outside the cell is 10 M, creating a 10,000-fold gradient of Ca concentrations across the cell membrane, separating the intracellular and extracellular solutions. When a cell is activated by external stimuli, the intracellular Ca concentration increases to levels of 10-10 M through Ca entry from the extracellular solution via plasma membrane Ca channels and/or Ca release from intracellular stores.

Association between vascular endothelial dysfunction and stroke incidence in the general Japanese population: Results from the tohoku medical megabank community-based cohort study.

Background: Flow-mediated dilation (FMD) measures vascular endothelial function by evaluating the vasodilatory response of blood vessels to increased blood flow. Nevertheless, the association between FMD and stroke incidence in a general population remains unclear. This study investigated the association between vascular endothelial function and stroke incidence in the general Japanese population.

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

Introduction: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction, and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population.

Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture.

Association between high-sensitivity cardiac troponin T levels and incident stroke in the elderly Japanese population: Results from the Tohoku Medical Megabank Community-based Cohort Study.

Elevated levels of circulating high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular disease. This study aimed to examine whether hs-cTnT levels are associated with incident stroke in the elderly population. The Iwate Tohoku Medical Megabank Organization pooled participant data for a community-based cohort study (n = 15,063, 69.

Association between total type I collagen N-terminal propeptide and coronary artery disease risk score in the general Japanese population.

Background: Bone metabolic dysregulation plays an important role in the pathogenesis of atherosclerosis; however, whether its markers contribute to coronary artery disease (CAD) risk in the general population remains unclear. Therefore, this study aimed to analyze the association between bone metabolic markers and CAD risk score in the general Japanese population.

Methods: The Iwate Medical Megabank Organization collected individual participant data during a community-based cohort study in the Iwate prefecture (n = 5,095, age = 58.

NLRP3 Inflammasome Inhibitor OLT1177 Suppresses Onset of Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis.

Background And Aims: NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects of OLT1177, a selective inhibitor of NLRP3 inflammasomes, in mice with dextran sulfate sodium (DSS)-induced colitis.

Methods: C57BL/6J mice were given drinking water containing 3% DSS for 5 days.

A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population.

Background: Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population.

Machine learning for effectively avoiding overfitting is a crucial strategy for the genetic prediction of polygenic psychiatric phenotypes.

The accuracy of previous genetic studies in predicting polygenic psychiatric phenotypes has been limited mainly due to the limited power in distinguishing truly susceptible variants from null variants and the resulting overfitting. A novel prediction algorithm, Smooth-Threshold Multivariate Genetic Prediction (STMGP), was applied to improve the genome-based prediction of psychiatric phenotypes by decreasing overfitting through selecting variants and building a penalized regression model. Prediction models were trained using a cohort of 3685 subjects in Miyagi prefecture and validated with an independently recruited cohort of 3048 subjects in Iwate prefecture in Japan.

Social Stress-Induced Postsynaptic Hyporesponsiveness in Glutamatergic Synapses Is Mediated by PSD-Zip70-Rap2 Pathway and Relates to Anxiety-Like Behaviors.

PSD-Zip70 is a postsynaptic protein that regulates glutamatergic synapse formation and maturation by modulation of Rap2 activity. PSD-Zip70 knockout (PSD-Zip70KO) mice exhibit defective glutamatergic synaptic transmission in the prefrontal cortex (PFC) with aberrant Rap2 activation. As prefrontal dysfunction is implicated in the pathophysiology of stress-induced psychiatric diseases, we examined PSD-Zip70KO mice in a social defeat (SD) stress-induced mouse model of depression to investigate stress-induced alterations in synaptic function.

Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study.

Background: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases.

Methods: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture.

The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project.

Background: Epidemiological studies have shown that high circulating cystatin C is associated with a risk of cardiovascular disease (CVD) independent of creatinine-based renal function measurements. The present study investigated the comparison between the cystatin C-based estimated glomerular filtration rate (GFRcys) and creatinine-based GFR (GFRcr) to determine whether these measurements are associated with CV biomarkers and elevated CVD risk in a general Japanese population.

Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 29,375).

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project.

Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population. The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture ( = 30,193, age = 60.

iMETHYL: an integrative database of human DNA methylation, gene expression, and genomic variation.

We launched an integrative multi-omics database, iMETHYL (http://imethyl.iwate-megabank.org).

Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies.

Epigenome-wide association studies, which searches for blood-based DNA methylation signatures associated with environmental exposures and/or disease susceptibilities, is a promising approach to a better understanding of the molecular aetiology of common diseases. To carry out large-scale epigenome-wide association studies while avoiding false negative detection, an efficient strategy to determine target CpG sites for microarray-based or sequencing-based DNA methylation profiling is essentially needed. Here, we propose and validate a hypothesis that a strategy focusing on CpG sites with high DNA methylation level variability may attain an improved efficacy.

Na/H exchange regulatory factor 1 is required for ROMK1 K channel expression in the surface membrane of cultured M-1 cortical collecting duct cells.

The ROMK1 K channel, a member of the ROMK channel family, is the major candidate for the K secretion pathway in the renal cortical collecting duct (CCD). ROMK1 possesses a PDZ domain-binding motif at its C-terminus that is considered a modulator of ROMK1 expression via interaction with Na/H exchange regulatory factor (NHERF) 1 and NHERF2 scaffold protein. Although NHERF1 is a potential binding partner of the ROMK1 K channel, the interaction between NHERF1 and K channel activity remains unclear.

Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score.

Background And Purpose: The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk.

Myocardin-related transcription factor A (MRTF-A) activity-dependent cell adhesion is correlated to focal adhesion kinase (FAK) activity.

The regulation of cell-substrate adhesion is tightly linked to the malignant phenotype of tumor cells and plays a role in their migration, invasion, and metastasis. Focal adhesions (FAs) are dynamic adhesion structures that anchor the cell to the extracellular matrix. Myocardin-related transcription factors (MRTFs), co-regulators of the serum response factor (SRF), regulate expression of a set of genes encoding actin cytoskeletal/FA-related proteins.

The Tohoku Medical Megabank Project: Design and Mission.

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members.

Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation.

Cytosine methylation at CpG dinucleotides is an epigenetic mechanism that affects the gene expression profiles responsible for the functional differences in various cells and tissues. Although gene expression patterns are dynamically altered in response to various stimuli, the intraindividual dynamics of DNA methylation in human cells are yet to be fully understood. Here, we investigated the extent to which DNA methylation contributes to the dynamics of gene expression by collecting 24 blood samples from two individuals over a period of 3 months.

Docosahexaenoic Acid Promotes Axon Outgrowth by Translational Regulation of Tau and Collapsin Response Mediator Protein 2 Expression.

n-3 PUFAs are essential for neuronal development and brain function. However, the molecular mechanisms underlying their biological effects remain unclear. Here we examined the mechanistic action of docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acids in the brain.

PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

Unlabelled: Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus.

Reduction of systematic bias in transcriptome data from human peripheral blood mononuclear cells for transportation and biobanking.

Transportation of samples is essential for large-scale biobank projects. However, RNA degradation during pre-analytical operations prior to transportation can cause systematic bias in transcriptome data, which may prevent subsequent biomarker identification. Therefore, to collect high-quality biobank samples for expression analysis, specimens must be transported under stable conditions.