The α-arrestin SUP-13/ARRD-15 promotes isoform turnover of actin-interacting protein 1 in striated muscle.

Precise arrangement of actin, myosin, and other regulatory components in a sarcomeric pattern is critical for producing contractile forces in striated muscles. Actin-interacting protein 1 (AIP1), also known as WD-repeat protein 1 (WDR1), is one of essential factors that regulate sarcomeric assembly of actin filaments. In the nematode , mutation in , encoding one of the two AIP1 isoforms, causes severe disorganization of sarcomeric actin filaments and near paralysis, but mutation in suppresses the mutant phenotypes to restore nearly normal sarcomeric actin organization and worm motility.

Alternative splicing of a single exon causes a major impact on the affinity of tropomyosin isoforms for actin filaments.

Tropomyosin is generally known as an actin-binding protein that regulates actomyosin interaction and actin filament stability. In metazoans, multiple tropomyosin isoforms are expressed, and some of them are involved in generating subpopulations of actin cytoskeleton in an isoform-specific manner. However, functions of many tropomyosin isoforms remain unknown.

Epigenetic profile of Japanese supercentenarians: a cross-sectional study.

Background: Centenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive research regarding the maintenance and reduction of epigenetic age has provided insights into increasing healthy longevity. To this end, we explored the epigenetic signatures reflecting hallmarks of exceptional healthy longevity, including avoidance of age-related diseases and cognitive functional decline.

Transition-Metal-Free Intermolecular Hydrocarbonation of Styrenes Mediated by NaH/1,10-Phenanthroline.

A transition-metal-free intermolecular coupling reaction of halocompounds with styrenes in the presence of NaH and 1,10-phenanthroline was developed. This reaction afforded hydrocarbonated products with complete anti-Markovnikov selectivity. The method allows the use of a wide range of halocompounds, including aryl and alkyl halides, and good functional group tolerance.

Epigenome-Wide Association Study Identified VTI1A DNA Methylation Associated With Accelerometer-Assessed Physical Activity.

Introduction: Health benefits of physical activity (PA) may be mediated by DNA methylation alterations. The purpose of the current study was to comprehensively identify CpG sites whose methylation levels were associated with accelerometer-assessed total PA in a general Japanese population.

Methods: The study participants were from the baseline survey of Saga Japan Multi-institutional Collaborative Cohort.

Evaluation of short-term epigenetic age fluctuation.

Considerable effort has been spent on lowering and maintaining the epigenetic age. However, the extent to which epigenetic age fluctuates under normal conditions is poorly understood. Therefore, we analyzed methylation data from monocytes and peripheral blood mononuclear cells collected from two Japanese men.

Mutual dependence between tropomodulin and tropomyosin in the regulation of sarcomeric actin assembly in Caenorhabditis elegans striated muscle.

Tropomodulin and tropomyosin are important components of sarcomeric thin filaments in striated muscles. Tropomyosin decorates the side of actin filaments and enhances tropomodulin capping at the pointed ends of the filaments. Their functional relationship has been extensively characterized in vitro, but in vivo and cellular studies in mammals are often complicated by the presence of functionally redundant isoforms.

Copper-catalyzed aerobic benzylic C(sp)-H lactonization of 2-alkylbenzamides N-centered radicals.

Herein, we describe the copper-catalyzed aerobic C(sp)-H functionalization of 2-alkylbenzamides for the synthesis of benzolactones. This reaction proceeds 1,5-hydrogen atom transfer of N-centered radicals directly generated by N-H bond cleavage and does not require the synthesis of pre-functionalized N-centered radical precursors or the use of strong stoichiometric oxidants.

Longitudinal DNA methylation dynamics as a practical indicator in clinical epigenetics.

Background: One of the fundamental assumptions of DNA methylation in clinical epigenetics is that DNA methylation status can change over time with or without interplay with environmental and clinical conditions. However, little is known about how DNA methylation status changes over time under ordinary environmental and clinical conditions. In this study, we revisited the high frequency longitudinal DNA methylation data of two Japanese males (24 time-points within three months) and characterized the longitudinal dynamics.

DNA Methylation Abnormalities and Altered Whole Transcriptome Profiles after Switching from Combustible Tobacco Smoking to Heated Tobacco Products.

Background: The use of heated tobacco products (HTP) has increased exponentially in Japan since 2016; however, their effects on health remain a major concern.

Methods: Tsuruoka Metabolome Cohort Study participants ( = 11,002) were grouped on the basis of their smoking habits as never smokers (NS), past smokers (PS), combustible tobacco smokers (CS), and HTP users for <2 years. Peripheral blood mononuclear cells were collected from 52 participants per group matched to HTP users using propensity scores, and DNA and RNA were purified from the samples.

Copper-catalyzed aerobic double functionalization of benzylic C(sp)-H bonds for the synthesis of 3-hydroxyisoindolinones.

A copper-catalyzed aerobic 3-hydroxyisoindolinone synthesis was developed via the benzylic double C(sp)-H functionalization of 2-alkylbenzamides. In this reaction, molecular oxygen was used as both an oxidant for C(sp)-H functionalization and an oxygen source. Our method can be extended to diverse benzylic C(sp)-H bonds and shows excellent functional group tolerance.

Evaluation of clinical formalin-fixed paraffin-embedded tissue quality for targeted-bisulfite sequencing.

Formalin-fixed paraffin-embedded (FFPE) tissues are promising biological resources for genetic research. Recent improvements in DNA extraction from FFPE samples allowed the use of these tissues for multiple sequencing methods. However, fundamental research addressing the application of FFPE-derived DNA for targeted-bisulfite sequencing (TB-seq) is lacking.

Two calponin-related proteins have overlapping functions that maintain cytoskeletal integrity and are essential for reproduction.

Multicellular organisms have multiple genes encoding calponins and calponin-related proteins, some of which are known to regulate actin cytoskeletal dynamics and contractility. However, the functional similarities and differences among these proteins are largely unknown. In the nematode , UNC-87 is a calponin-related protein with seven calponin-like (CLIK) motifs and is required for maintenance of contractile apparatuses in muscle cells.

Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5).

Lamotrigine (LTG) is an important antiepileptic drug for the treatment of seizures in pregnant women with epilepsy. However, it is not known if the transport of LTG into placental cells occurs via a carrier-mediated pathway. The aim of this study was to investigate the uptake properties of LTG into placental cell lines (BeWo and JEG-3), and to determine the involvement of organic cation transporters (OCTs, SLC22A1-3) and organic cation/carnitine transporter (OCTNs, SLC22A4-5) in the uptake process.

Solventless-mixing tablet coating technique using a V-shaped blender; investigation using methyl methacrylate and diethylaminoethyl methacrylate copolymer powder.

Our aim was to investigate the feasibility of a tablet coating mixing technique using a V-shaped blender to produce coated tablets by mixing only tablets and polymer powder. Tablet coating was achieved as follows. First, polymethacrylate latex was freeze-dried to prepare a coating powder.

Kettin, the large actin-binding protein with multiple immunoglobulin domains, is essential for sarcomeric actin assembly and larval development in Caenorhabditis elegans.

Among many essential genes in the nematode Caenorhabditis elegans, let-330 is located on the left arm of chromosome V and was identified as the largest target of a mutagen in this region. However, let-330 gene has not been characterized at the molecular level. Here, we report that two sequenced let-330 alleles are nonsense mutations of ketn-1, a previously characterized gene encoding kettin.

Mutations in actin, which are equivalent to human cardiomyopathy mutations, cause abnormal actin aggregation in nematode striated muscle.

Actin is a central component of muscle contractile apparatuses, and a number of actin mutations cause diseases in skeletal, cardiac, and smooth muscles. However, many pathogenic actin mutations have not been characterized at cell biological and physiological levels. In this study, we tested whether the nematode could be used to characterize properties of actin mutants in muscle cells .

Analysis of the effects of polyunsaturated fatty acids on transporter expressions using a PCR array: Induction of xCT/SLC7A11 in human placental BeWo cells.

Objective: Polyunsaturated fatty acids (PUFAs), including arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are essential for adequate fetal growth. The aim of the present study was to elucidate the effects of PUFAs on the expression and function of placental transporters, which play important roles in placental functions including the supply of nutrients to the fetus, excretion of metabolites, and protection of the fetus from xenobiotics.

Methods: Human placental choriocarcinoma BeWo cells were used as a trophoblast model.

Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematode Caenorhabditis elegans.

Tropomyosin, one of the major actin filament-binding proteins, regulates actin-myosin interaction and actin-filament stability. Multicellular organisms express a number of tropomyosin isoforms, but understanding of isoform-specific tropomyosin functions is incomplete. The nematode Caenorhabditis elegans has a single tropomyosin gene, lev-11, which has been reported to express four isoforms by using two separate promoters and alternative splicing.

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.

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.

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.