Validity of the copper/zinc ratio as a diagnostic marker for taste disorders associated with zinc deficiency.

Although zinc (Zn) deficiency is often suspected in patients with taste disorders, it may be difficult to diagnose Zn deficiency, especially in patients without any clear risk factors. Accordingly, the aim of the present study was to detect possible markers for taste disorders or zinc deficiency. To achieve this aim, we analyzed data obtained from 122 Japanese men who were not using medicines and had no diseases requiring treatment.

Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.

The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality.

Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy.

Amiodarone hydrochloride (AMD), an anti-arrhythmic agent, has been shown to cause peripheral neuropathy; however, its pathogenesis remains unknown. We examined the toxic effects of AMD on an immortalized adult rat Schwann cell line, IFRS1, and cocultures of IFRS1 cells and adult rat dorsal root ganglion neurons or nerve growth factor-primed PC12 cells. Treatment with AMD (1, 5, and 10 μm) induced time- and dose-dependent cell death, accumulation of phospholipids and neutral lipids, upregulation of the expression of gangliosides, and oxidative stress (increased nuclear factor E2-related factor in nuclear extracts and reduced GSH/GSSG ratios) in IFRS1 cells.

Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition.

Combined DECS Analysis and Next-Generation Sequencing Enable Efficient Detection of Novel Plant RNA Viruses.

The presence of high molecular weight double-stranded RNA (dsRNA) within plant cells is an indicator of infection with RNA viruses as these possess genomic or replicative dsRNA. DECS (dsRNA isolation, exhaustive amplification, cloning, and sequencing) analysis has been shown to be capable of detecting unknown viruses. We postulated that a combination of DECS analysis and next-generation sequencing (NGS) would improve detection efficiency and usability of the technique.

Reduced Biaxial Contractility in the Descending Thoracic Aorta of Fibulin-5 Deficient Mice.

The precise role of smooth muscle cell contractility in elastic arteries remains unclear, but accumulating evidence suggests that smooth muscle dysfunction plays an important role in the development of thoracic aortic aneurysms and dissections (TAADs). Given the increasing availability of mouse models of these conditions, there is a special opportunity to study roles of contractility ex vivo in intact vessels subjected to different mechanical loads. In parallel, of course, there is a similar need to study smooth muscle contractility in models that do not predispose to TAADs, particularly in cases where disease might be expected.

Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro.

The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods.

Structure and function of outer dynein arm intermediate and light chain complex.

The outer dynein arm (ODA) is a molecular complex that drives the beating motion of cilia/flagella. Chlamydomonas ODA is composed of three heavy chains (HCs), two ICs, and 11 light chains (LCs). Although the three-dimensional (3D) structure of the whole ODA complex has been investigated, the 3D configurations of the ICs and LCs are largely unknown.

Au Nanoparticle-Embedded Carbon Films for Electrochemical As(3+) Detection with High Sensitivity and Stability.

Au nanoparticle (AuNP)-embedded carbon films were formed with a one-step reproducible process by using unbalanced magnetron (UBM) cosputtering to make it possible to detect As(3+) in water. The sputtered Au components formed NPs (typically 5 nm in diameter) spontaneously in the carbon films, owing to the poor intermiscibility of Au with carbon. The surface contents of embedded AuNPs in the carbon film were widely controllable (Au = 13-21 at %) by regulating the target powers of Au and carbon individually.

The combined effect of visit-to-visit variability in HbA1c and systolic blood pressure on the incidence of cardiovascular events in patients with type 2 diabetes.

Objective: To investigate the association between long-term visit-to-visit variability in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) and the incidence of cardiovascular disease (CVD) in patients with type 2 diabetes.

Methods: We retrospectively enrolled 632 patients with type 2 diabetes and no history of CVD who first visited our hospital between 1995 and 1996, were followed-up for ≥1 year, attended at least 4 clinic visits and had at least 1 visit per year. Patients were followed until June 2012 at the latest, and mailed questionnaires.

Fibulin-5 Blocks Microenvironmental ROS in Pancreatic Cancer.

Elevated oxidative stress is an aberration seen in many solid tumors, and exploiting this biochemical difference has the potential to enhance the efficacy of anticancer agents. Homeostasis of reactive oxygen species (ROS) is important for normal cell function, but excessive production of ROS can result in cellular toxicity, and therefore ROS levels must be balanced finely. Here, we highlight the relationship between the extracellular matrix and ROS production by reporting a novel function of the matricellular protein Fibulin-5 (Fbln5).

Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice.

Smooth muscle cells (SMCs) and the extracellular matrix (ECM) are intimately associated in the aortic wall. Fbln4(SMKO) mice with an SMC-specific deletion of the Fbln4 gene, which encodes the vascular ECM component fibulin-4, develop ascending aortic aneurysms that have increased abundance of angiotensin-converting enzyme (ACE); inhibiting angiotensin II signaling within the first month of life prevents aneurysm development. We used comparative proteomics analysis of Fbln4(SMKO) aortas from postnatal day (P) 1 to P30 mice to identify key molecules involved in aneurysm initiation and expansion.

On-Chip Sequence-Specific Immunochemical Epigenomic Analysis Utilizing Outward-Turned Cytosine in a DNA Bulge with Handheld Surface Plasmon Resonance Equipment.

This paper reports a sequence-specific immunoassay chip for DNA methylation assessment by microfluidic-based surface plasmon resonance (SPR) detection. This was achieved by utilizing an affinity measurement involving the target, (methyl)cytosine, in a single-base bulge region and an anti-methylcytosine antibody in a microchannel, following hybridization with a biotinylated bulge-inducing DNA probe. The probe alters the target cytosine in a looped-out state because of the π-π stacking between flanking bases of the target.

Prospective intervention study with a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene system) for the rapid diagnosis of bloodstream infections, and its impact on the clinical outcomes.

The Verigene Gram-positive blood culture test (BC-GP) and the Verigene Gram-negative blood culture test (BC-GN) identify representative Gram-positive bacteria, Gram-negative bacteria and their antimicrobial resistance by detecting resistance genes within 3 h. Significant benefits are anticipated due to their rapidity and accuracy, however, their clinical utility is unproven in clinical studies. We performed a clinical trial between July 2014 and December 2014 for hospitalized bacteremia patients.

Axonemal dynein light chain-1 locates at the microtubule-binding domain of the γ heavy chain.

The outer arm dynein (OAD) complex is the main propulsive force generator for ciliary/flagellar beating. In Chlamydomonas and Tetrahymena, the OAD complex comprises three heavy chains (α, β, and γ HCs) and >10 smaller subunits. Dynein light chain-1 (LC1) is an essential component of OAD.

Multicenter evaluation of the Verigene Gram-negative blood culture nucleic acid test for rapid detection of bacteria and resistance determinants in positive blood cultures.

The Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) is a microarray-based assay that enables rapid detection of 9 common Gram-negative bacteria and 6 resistance determinants directly from positive blood cultures. We compared the performance of BC-GN with currently used automated systems, testing 141 clinical blood cultures and 205 spiked blood cultures. For identification of BC-GN target organisms in clinical and spiked blood cultures, the BC-GN assay showed 98.

Molecular basis of cleft palates in mice.

Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo.

Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.

Homozygous recessive mutations in either EFEMP2 (encoding fibulin-4) or FBLN5 (encoding fibulin-5), critical genes for elastogenesis, lead to autosomal recessive cutis laxa types 1B and 1A, respectively. Previously, fibulin-4 was shown to bind lysyl oxidase (LOX), an elastin/collagen cross-linking enzyme, in vitro. Consistently, reported defects in humans with EFEMP2 mutations are more severe and broad in range than those due to FBLN5 mutations and encompass both elastin-rich and collagen-rich tissues.

Effect of the sp(2)/sp(3) Ratio in a Hybrid Nanocarbon Thin Film Electrode for Anodic Stripping Voltammetry Fabricated by Unbalanced Magnetron Sputtering Equipment.

The effect of the sp(2)/sp(3) ratio in an unbalanced magnetron sputtered nanocarbon film electrode was studied for determining Cd(2+) and Pb(2+) by anodic stripping voltammetry (ASV). The signal-to-noise ratio in the ASV measurement improved as the sp(3) concentration in the carbon film increased because the noise current decreased with the increasing sp(3) concentration. The detection limits with a carbon film containing 50% sp(3) were 0.

Physical and physiological effectiveness of an overall health care program for middle-aged Japanese women with mild obesity: A pilot study.

This study aimed to verify the effectiveness of an overall health care program (OHCP) for middle-aged Japanese women through assessing physical and physiological changes. The OHCP consisted of diet modification with natural alternative foods, walking and stretching exercises, and body massage and cupping treatments. Sixty-seven participants were assigned to one of three groups during a 3-year study period (2011-2013).

TGF-β-Dependent Dendritic Cell Chemokinesis in Murine Models of Airway Disease.

Small airway chronic inflammation is a major pathologic feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Dendritic cells (DCs) accumulate around small airways in COPD. DCs are critical mediators of Ag surveillance and Ag presentation and amplify adaptive immune responses.

ECHO-liveFISH: in vivo RNA labeling reveals dynamic regulation of nuclear RNA foci in living tissues.

Elucidating the dynamic organization of nuclear RNA foci is important for understanding and manipulating these functional sites of gene expression in both physiological and pathological states. However, such studies have been difficult to establish in vivo as a result of the absence of suitable RNA imaging methods. Here, we describe a high-resolution fluorescence RNA imaging method, ECHO-liveFISH, to label endogenous nuclear RNA in living mice and chicks.

Palliative surgical treatment for cutaneous metastatic tumor is a valid option for improvement of quality of life.

A cutaneous metastatic tumor is relatively rare, and patients with such a tumor usually have a poor prognosis. Even if the metastases can be treated, the treatment cannot improve the prognosis. However, neglecting metastatic lesions sometimes results in a great deterioration of quality of life.