1/ f Fluctuations of amino acids regulate water transportation in aquaporin 1.

Aquaporins (AQPs), which transport water molecules across cell membranes, are involved in many physiological processes. Recently, it is reported that the water-water interactions within the channel are broken at the aromatic/arginine selectivity filter (ar/R region), which prevents proton transportation [U. K.

Association between endometriosis and the interleukin 1A (IL1A) locus.

Study Question: Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk?

Summary Answer: We found evidence for strong association between IL1A SNPs and endometriosis risk.

What Is Known Already: Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci.

Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.

Through genome-wide association analysis and an independent replication study using a total of 1131 bladder cancer cases and 12 558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P-value of 4.

Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate.

Background: Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1-20.

Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation.

DNA methylation is a central epigenetic modification in mammals, with essential roles in development and disease. De novo DNA methyltransferases establish DNA methylation patterns in specific regions within the genome by mechanisms that remain poorly understood. Here we show that protein citrullination by peptidylarginine deiminase 4 (PADI4) affects the function of the DNA methyltransferase DNMT3A.

Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism.

Treatment success of chronic hepatitis C virus genotype 1 infection has improved with the advent of telaprevir plus peg-interferon/ribavirin triple combination therapy. However, the effect of inosine triphosphatase (ITPA) polymorphism on dose reduction during triple therapy, especially during the postmarketing phase, has not been sufficiently evaluated. We analysed 273 patients with genotype 1 infection who were treated with triple therapy and assessed the effect of the ITPA polymorphism on dose reduction.

A rare polymorphic variant of NBS1 reduces DNA repair activity and elevates chromosomal instability.

Failure to expeditiously repair DNA at sites of double-strand breaks (DSB) ultimately is an important etiologic factor in cancer development. NBS1 plays an important role in the cellular response to DSB damage. A rare polymorphic variant of NBS1 that resulted in an isoleucine to valine substitution at amino acid position 171 (I171V) was first identified in childhood acute lymphoblastic leukemia.

Genome-wide association studies of atopic dermatitis.

Atopic dermatitis is a common inflammatory disease caused by a combination of genetic and environmental factors. Genome-wide association study (GWAS) is a comprehensive and unbiased approach to identify the genetic components of human diseases and to discover the cellular pathways underlying them. GWAS and recent immunochip analysis of atopic dermatitis have identified a total of 19 associated loci with a genome-wide level of significance (P < 5 × 10(-8) ).

One-dimensional α condensation of α-linear-chain states in ¹²C and ¹⁶O.

We present a new picture that the α-linear-chain structure for 12C and 16O has one-dimensional α condensate character. The wave functions of linear-chain states that are described by superposing a large number of Brink wave functions have extremely large overlaps of nearly 100% with single Tohsaki-Horiuchi-Schuck-Röpke wave functions, which were proposed to describe the α condensed "gaslike" states. Although this new picture is different from the conventional idea of the spatial localization of α clusters, the density distributions are shown to have localized α clusters due to the inter-α Pauli repulsion.

A 1.7 nm resolution chemical analysis of carbon nanotubes by tip-enhanced Raman imaging in the ambient.

Surface morphology of materials is routinely analysed by an atomic force microscope and scanning tunneling microscope (STM) down to subnanometer precision. However, it is still challenging to investigate the surface chemistry simultaneously, which requires specific capability of force or tunneling spectroscopy in ultrahigh vacuum environment and liquid Helium temperature. Here we demonstrate the simultaneous chemical and structural analysis of individual carbon nanotubes (CNTs) by STM-based tip-enhanced Raman spectroscopy (STM-TERS) with 1.

Lung functions of Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery.

Background: Chronic rhinosinusitis (CRS), which is clinically classified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), shows considerable geographic differences and heterogeneity. Eosinophilic (E) CRS with nasal polyps (ECRSwNP) has a higher degree of disease severity and higher frequency of comorbid asthma. Epidemiologic studies in different ethnic populations have improved understanding of the pathophysiology of the disease.

Direct electrochemistry and intramolecular electron transfer of ascorbate oxidase confined on L-cysteine self-assembled gold electrode.

A direct electrochemistry and intramolecular electron transfer of multicopper oxidases are of a great importance for the fabrication of these enzyme-based bioelectrochemical-devices. Ascorbate oxidase from Acremonium sp. (ASOM) has been successfully immobilized via a chemisorptive interaction on the l-cysteine self-assembled monolayer modified gold electrode (cys-SAM/AuE).

Genome-wide association study of breast cancer in the Japanese population.

Breast cancer is the most common malignancy among women in worldwide including Japan. Several studies have identified common genetic variants to be associated with the risk of breast cancer. Due to the complex linkage disequilibrium structure and various environmental exposures in different populations, it is essential to identify variants associated with breast cancer in each population, which subsequently facilitate the better understanding of mammary carcinogenesis.

Immunotherapy with artificial adjuvant vector cells: Harnessing both arms of the immune response.

Both innate and adaptive immunity underpin cancer immunosurveillance. To stimulate both these arms of the immune system, we used allogeneic cells loaded with natural killer T (NKT) cell ligands and expressing tumor-associated antigens, resulting in NKT cell activation, dendritic-cell maturation and ultimately in the elicitation of adaptive T-cell responses. This approach holds great promise for the development of novel anticancer immunotherapies.

Improving quantum gate fidelities by using a qubit to measure microwave pulse distortions.

We present a new method for determining pulse imperfections and improving the single-gate fidelity in a superconducting qubit. By applying consecutive positive and negative π pulses, we amplify the qubit evolution due to microwave pulse distortions, which causes the qubit state to rotate around an axis perpendicular to the intended rotation axis. Measuring these rotations as a function of pulse period allows us to reconstruct the shape of the microwave pulse arriving at the sample.

A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.

Background & Aims: Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect the risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population.

Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells.

Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, α-galactosylceramide (α-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand α-GalCer and then transfected with antigen-encoding mRNA.

The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells.

Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous administration of the cytokine RANKL can synchronously activate M-cell differentiation in mice.

Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clusters requires further genome-wide analyses based on a dense SNP set and comparison of haplotype frequencies. In the present study, we determined haplotypes for the Hondo cluster of the Japanese population by detecting SNP homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the haplotype frequencies.

Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD.

Strong coupling between 4f valence instability and 3d ferromagnetism in Yb(x)Fe4Sb12 studied by resonant x-ray emission spectroscopy.

We have investigated the temperature and pressure dependency of the electronic structure of Yb-filled skutterudites, YbFe(4)Sb(12) and Yb(0.88)Fe(4)Sb(12), using x-ray absorption and emission spectroscopies. An anomalous increase of the Yb valence, which is beyond the conventional Anderson model picture, is found to coincide with the onset of the ferromagnetic order in the x=0.

Analysis of aquaporin-mediated diffusional water permeability by coherent anti-stokes Raman scattering microscopy.

Water can pass through biological membranes via two pathways: simple diffusion through the lipid bilayer, or water-selective facilitated diffusion through aquaporins (AQPs). Although AQPs play an important role in osmotic water permeability (P(f)), the role of AQPs in diffusional water permeability remains unclear because of the difficulty of measuring diffusional water permeability (P(d)). Here, we report an accurate and instantaneous method for measuring the P(d) of a single HeLa S3 cell using coherent anti-Stokes Raman scattering (CARS) microscopy with a quick perfusion device for H(2)O/D(2)O exchange.

Insight from genome-wide association studies in rheumatoid arthritis and multiple sclerosis.

Autoimmune diseases are caused by multiple genes and environmental effects. In addition, genetic contributions and the number of associated genes differ among different diseases and ethnic populations. Genome-wide association studies (GWAS) on rheumatoid arthritis (RA) and multiple sclerosis (MS) show that these diseases share many genetic factors.

Prolonged antitumor NK cell reactivity elicited by CXCL10-expressing dendritic cells licensed by CD40L+ CD4+ memory T cells.

Immunotherapy using dendritic cells (DCs) has the potential to activate both T cells and NK cells. We previously demonstrated the long-lasting antitumor responses by NK cells following immunization with bone marrow-derived DCs. In the current study, we demonstrate that long-term antitumor NK responses require endogenous DCs and a subset of effector memory CD4(+) T (CD4(+) T(EM)) cells.