Obscurin Rho GEF domains are phosphorylated by MST-family kinases but do not exhibit nucleotide exchange factor activity towards Rho GTPases in vitro.

Obscurin is a giant muscle protein (>800 kDa) featuring multiple signalling domains, including an SH3-DH-PH domain triplet from the Trio-subfamily of guanosine nucleotide exchange factors (GEFs). While previous research suggests that these domains can activate the small GTPases RhoA and RhoQ in cells, in vitro characterization of these interactions using biophysical techniques has been hampered by the intrinsic instability of obscurin GEF domains. To study substrate specificity, mechanism and regulation of obscurin GEF function by individual domains, we successfully optimized recombinant production of obscurin GEF domains and found that MST-family kinases phosphorylate the obscurin DH domain at Thr5798.

Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cortex.

The cell cortex is a dynamic assembly that ensures cell integrity during passive deformation or active response by adapting cytoskeleton topologies with poorly understood mechanisms. The spectrin meshwork ensures such adaptation in erythrocytes and neurons. Erythrocytes rely on triangular-like lattices of spectrin tetramers, which in neurons are organized in periodic arrays.

Improvement in arterial enhancement using diluted injection of contrast medium in CT angiography.

Background: Arterial enhancement after contrast injection affects the quality of computed tomography angiography (CTA) images.

Purpose: To evaluate whether the dilution of contrast medium (CM) for CTA increases arterial enhancement after the adjustment of iodine concentration as per the patient's body weight (BW).

Material And Methods: We retrospectively studied 700 patients who underwent coronary CTA.

Making sense of missense variants in TTN-related congenital myopathies.

Mutations in the sarcomeric protein titin, encoded by TTN, are emerging as a common cause of myopathies. The diagnosis of a TTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence of TTN variants in control populations. Here, we present a combined clinico-pathological, genetic and biophysical approach to the diagnosis of TTN-related myopathies and the pathogenicity ascertainment of TTN missense variants.

When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.

Obscurin is a giant muscle protein that connects the sarcomere with the sarcoplasmic reticulum, and has poorly understood structural and signalling functions. Increasingly, obscurin variants are implicated in the pathophysiology of cardiovascular diseases. The Arg4344Gln variant (R4344Q) in obscurin domain Ig58, initially discovered in a patient with hypertrophic cardiomyopathy, has been reported to reduce binding to titin domains Z8-Z9, impairing obscurin's Z-disc localization.

Three-year effects of neighborhood social network intervention on mental and physical health of older adults.

Objectives: Although neighborhood is considered to be a crucial source of social network to promote health among older adults, current findings are mostly derived from observational study designs. This study examined whether participations in event-based community programs could increase neighborhood social network and whether such increase could lead to desirable changes in mental and physical health among older adults.

Method: This study employed quasi-experimental design.

Social Interaction in Walking Groups and Affective Responses Among Japanese Older Adults.

This study examined whether satisfaction with social interactions and the number of people interacted with during walking groups is associated with affective responses among older adults. Twenty-six older adults were asked to participate in five walking group sessions. The participants walked together for 40-50 min.

[Effect of Tube Voltage on Contrast Enhancement and Contrast Medium Dose in Abdominal Contrast-enhanced Computed Tomography].

The purpose of this study was to investigate the effect of tube voltage on relationship between a patient's body weight and contrast enhancement in abdominal contrast-enhanced computed tomography (CT). Five phantoms with diameters ranging from 19.2 to 30.

Frequency of going outdoors and health-related quality of life among older adults: Examining the moderating role of living alone and employment status.

Aim: Going outdoors more frequently is beneficial for maintaining and improving health-related quality of life (HRQOL) among older adults. However, individual differences can alter the effects of going outdoors. The present study aimed to examine whether relationships between going outdoors and HRQOL were moderated by living alone and employment status.

Community intervention to increase neighborhood social network among Japanese older adults.

Aim: Strengthening neighborhood social networks is important for promoting health among older adults. However, effective intervention strategies aimed at increasing older adults' social networks have not yet been established. The present study examined whether a university-led community intervention that provided communication opportunities could increase older Japanese adults' neighborhood social networks.

Binding of Myomesin to Obscurin-Like-1 at the Muscle M-Band Provides a Strategy for Isoform-Specific Mechanical Protection.

The sarcomeric cytoskeleton is a network of modular proteins that integrate mechanical and signaling roles. Obscurin, or its homolog obscurin-like-1, bridges the giant ruler titin and the myosin crosslinker myomesin at the M-band. Yet, the molecular mechanisms underlying the physical obscurin(-like-1):myomesin connection, important for mechanical integrity of the M-band, remained elusive.

Binding partners of the kinase domains in Drosophila obscurin and their effect on the structure of the flight muscle.

Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains.

The crystal structure of the human titin:obscurin complex reveals a conserved yet specific muscle M-band zipper module.

M10 is the most C-terminal immunoglobulin (Ig) domain of the giant protein titin and a frequent target of disease-linked mutations. Currently, it is the only known muscle Ig domain able to interact with two alternative ligands-obscurin and obscurin-like-1 (Obsl1)-in different sarcomeric subregions. Obscurin and Obsl1 use their homologous N-terminal Ig domain (O1 in obscurin and OL1 in Obsl1) to bind M10 in a mutually exclusive manner.

[Survey regarding mental health conditions of high school students and attitudes of students and their teachers toward students' mental health issues].

We administered a self-reporting questionnaire survey regarding the mental health conditions of high school students and attitudes of students and their teachers toward students' mental health issues. In addition, we discussed the requirements for high school students' mental health support system. The subjects were 3,312 students and 208 teachers in four Shizuoka prefectural public high schools in 2009.

[Assessment of the effects of administering a saline solution flush after contrast medium injection using different injection durations and flush methods].

The purpose of administering a saline solution flush after contrast medium injection is to more effectively utilize the contrast medium remaining in the vessels from the subclavian vein to the superior vena cava. In order to investigate the effects of administering a saline solution flush after a contrast medium injection, we evaluated the effects of various contrast medium injection durations and injection methods on the time-density curve (TDC) using a custom-made TDC measurement phantom. The TDC was found to have a biphasic appearance, showing a rapid increase after the arrival of contrast medium in the target region followed by a slower increase from an inflection point at 25 s after the start of contrast medium injection, reflecting the differences in circulatory dynamics for each duration.

The positivity scale.

Five studies document the validity of a new 8-item scale designed to measure positivity, defined as the tendency to view life and experiences with a positive outlook. In the first study (N = 372), the psychometric properties of Positivity Scale (P Scale) were examined in accordance with classical test theory using a large number of college participants. In Study 2, the unidimensionality of the P Scale was corroborated with confirmatory factor analysis in 2 independent samples (N₁ = 322; N₂ = 457).

Physicochemical characteristics of rapidly dried onion powder and its anti-atherogenic effect on rats fed high-fat diet.

Rapidly dried onion (Allium cepa L. cv. Momiji No.

Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.

In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin form a ternary complex that is crucial for the function of the M-band as a mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10, which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to hereditary muscle diseases. The M10 domain is unusual not only in that it is a frequent target of disease-linked mutations, but also in that it is the only currently known muscle Ig-domain that interacts with two ligands--obscurin and obsl1--in different sarcomeric subregions.

Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band: implications for hereditary myopathies.

Obscurin, a giant modular muscle protein implicated in G-protein and protein-kinase signalling, can localize to both sarcomeric Z-disks and M-bands. Interaction of obscurin with the Z-disk is mediated by Z-disk titin. Here, we unravel the molecular basis for the unusual localization of obscurin, a Z-disk-associated protein, to the M-band, where its invertebrate analogue UNC-89 is also localized.

Cellular and molecular characterization of an embryonic cell line (BME26) from the tick Rhipicephalus (Boophilus) microplus.

The cellular and molecular characteristics of a cell line (BME26) derived from embryos of the cattle tick Rhipicephalus (Boophilus) microplus were studied. The cells contained glycogen inclusions, numerous mitochondria, and vesicles with heterogeneous electron densities dispersed throughout the cytoplasm. Vesicles contained lipids and sequestered palladium meso-porphyrin (Pd-mP) and rhodamine-hemoglobin, suggesting their involvement in the autophagic and endocytic pathways.

The role of hemocytes in the immunity of the spider Acanthoscurria gomesiana.

Invertebrates protect themselves against microbial infection through cellular and humoral immune defenses. Since the available information on the immune system of spiders is scarce, the main goal of the present study was to investigate the role of hemocytes and antimicrobial peptides (AMPs) in defense against microbes of spider Acanthoscurria gomesiana. We previously described the purification and characterization of two AMPs from the hemocytes of naïve spider A.

Complete human gene structure of obscurin: implications for isoform generation by differential splicing.

The complete gene giant muscle protein obscurin, a modular protein composed largely of tandem Ig-domains, GDP/GTP exchange factor domains (GEF) for small G-proteins, and differentially spliced kinase domains, was analysed. The splice donor and acceptor sites of the 117 exons give important clues for potential splice pathways. The fusion of the conventional obscurin A, containing only the GEF domain, and obscurin B, fusing into the 3' kinase exons, was experimentally confirmed and analysed.

Partial sequence of connectin-like 1200K-protein in obliquely striated muscle of a polychaete (Annelida): evidence for structural diversity from vertebrate and invertebrate connectins.

Vertebrate striated muscle contains the giant elastic protein connectin that maintains the position of the A-band at the center of the sarcomere during repeated muscular contraction and relaxation. Connectin-like molecules may perform conserved functions in vertebrate and invertebrate striated and oblique muscles, although less is known about the structure of invertebrate connectins at present. The protein that maintains such a structure is present not only in vertebrate striated muscle, but also in invertebrate striated and oblique muscle.

The entire cDNA sequences of projectin isoforms of crayfish claw closer and flexor muscles and their localization.

Projectin is a giant protein related to twitchin and titin/connectin, that is found in arthropod striated muscle. The complete sequence of a 1 MDa projectin from Drosophila muscle was recently deduced from a thorough analysis of the genomic DNA (Southgate and Ayme-Southgate, 2001). Here we report the complete sequence for projectin from crayfish claw closer muscle (8625 residues; 962,634 Da).

Molecular cloning, expression analysis and cellular localization of gomesin, an anti-microbial peptide from hemocytes of the spider Acanthoscurria gomesiana.

Gomesin is a cationic anti-microbial peptide of 18 amino acid residues isolated from the hemocytes of unchallenged tarantula spider Acanthoscurria gomesiana. This paper reports the first study of the processing and cellular location of an anti-microbial peptide (AMP) in spiders. Gomesin cDNA sequence analysis indicated that it is processed from a precursor containing a signal peptide (23 amino acid residues) and a negative C-terminal region (43 amino acid residues).