A genome-wide association study of copy-number variation identifies putative loci associated with osteoarthritis in Koreans

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background OA is a complex disease caused by environmental and genetic risk factors. The purpose of this study is to identify candidate copy number variations (CNVs) associated with OA. Methods We performed a genome-wide association study of CNV to identify potential loci that confer susceptibility to or protection from OA. CNV genotyping was conducted using NimbleGen HD2 3 × 720K comparative hybridization array and included samples from 371 OA patients and 467 healthy controls. The putative CNV regions identified were confirmed with a TaqMan assay. Results We identified six genomic regions associated with OA encompassing CNV loci. None of six loci had previously been reported in genome-wide association studies with OA, although a genetic analysis suggested that they have functional effects. The protein product of a candidate risk gene for obesity, TNKS, targets Wnt inhibition, and this gene was significantly associated with hand and knee OA. Copy number deletion on TNKS was associated with a 1.37-fold decreased risk for OA. In addition, CA10, which shows a strong association with osteoporosis, was also significant in our study. Copy number deletion on this gene was associated with a 1.69-fold decreased risk for OA. Conclusion We identified several CNV loci that may contribute to OA susceptibility in Koreans. Further functional investigations of these genes are warranted to fully characterize their putative association

Inhibition of Wnt/β-Catenin Signaling by a Soluble Collagen-Derived Frizzled Domain Interacting with Wnt3a and the Receptors Frizzled 1 and 8

The Wnt/β-catenin pathway controls cell proliferation, death and differentiation. Several families of extracellular proteins can antagonize Wnt/β-catenin signaling, including the decoy receptors known as secreted frizzled related proteins (SFRPs), which have a cysteine-rich domain (CRD) structurally similar to the extracellular Wnt-binding domain of the frizzled receptors. SFRPs inhibit Wnt signaling by sequestering Wnts through the CRD or by forming inactive complexes with the frizzled receptors. Other endogenous molecules carrying frizzled CRDs inhibit Wnt signaling, such as V3Nter, which is proteolytically derived from the cell surface component collagen XVIII and contains a biologically active frizzled domain (FZC18) inhibiting in vivo cell proliferation and tumor growth in mice. We recently showed that FZC18 expressing cells deliver short-range signals to neighboring cells, decreasing their proliferation in vitro and in vivo through the Wnt/β-catenin signaling pathway. Here, using low concentrations of soluble FZC18 and Wnt3a, we show that they physically interact in a cell-free system. In addition, soluble FZC18 binds the frizzled 1 and 8 receptors' CRDs, reducing cell sensitivity to Wnt3a. Conversely, inhibition of Wnt/β-catenin signaling was partially rescued by the expression of full-length frizzled 1 and 8 receptors, but enhanced by the expression of a chimeric cell-membrane-tethered frizzled 8 CRD. Moreover, soluble, partially purified recombinant FZC18_CRD inhibited Wnt3a-induced β-catenin activation. Taken together, the data indicate that collagen XVIII-derived frizzled CRD shifts Wnt sensitivity of normal cells to a lower pitch and controls their growth

Design of Highly Selective Gas Sensors via Physicochemical Modification of Oxide Nanowires: Overview

Strategies for the enhancement of gas sensing properties, and specifically the improvement of gas selectivity of metal oxide semiconductor nanowire (NW) networks grown by chemical vapor deposition and thermal evaporation, are reviewed. Highly crystalline NWs grown by vapor-phase routes have various advantages, and thus have been applied in the field of gas sensors over the years. In particular, n-type NWs such as SnO2, ZnO, and In2O3 are widely studied because of their simple synthetic preparation and high gas response. However, due to their usually high responses to C2H5OH and NO2, the selective detection of other harmful and toxic gases using oxide NWs remains a challenging issue. Various strategies—such as doping/loading of noble metals, decorating/doping of catalytic metal oxides, and the formation of core–shell structures—have been explored to enhance gas selectivity and sensitivity, and are discussed herein. Additional methods such as the transformation of n-type into p-type NWs and the formation of catalyst-doped hierarchical structures by branch growth have also proven to be promising for the enhancement of gas selectivity. Accordingly, the physicochemical modification of oxide NWs via various methods provides new strategies to achieve the selective detection of a specific gas, and after further investigations, this approach could pave a new way in the field of NW-based semiconductor-type gas sensors

Global mapping of the regulatory interactions of histone residues

AbstractHistone residues can serve as platforms for specific regulatory function. Here we constructed a map of regulatory associations between histone residues and a wide spectrum of chromatin regulation factors based on gene expression changes by histone point mutations in Saccharomyces cerevisiae. Detailed analyses of this map revealed novel associations. Regarding the modulation of H3K4 and K36 methylation by Set1, Set2, or Jhd2, we proposed a role for H4K91 acetylation in early Pol II elongation, and for H4K16 deacetylation in late elongation and crosstalk with H3K4 demethylation for gene silencing. The association of H3K56 with nucleosome positioning suggested that this lysine residue and its acetylation might contribute to nucleosome mobility for transcription activation. Further insights into chromatin regulation are expected from this approach

Co-Doped Branched ZnO Nanowires for Ultraselective and Sensitive Detection of Xylene

Co-doped branched ZnO nanowires were prepared by multistep vapor-phase reactions for the ultraselective and sensitive detection of <i>p</i>-xylene. Highly crystalline ZnO NWs were transformed into CoO NWs by thermal evaporation of CoCl₂ powder at 700 °C. The Co-doped ZnO branches were grown subsequently by thermal evaporation of Zn metal powder at 500 °C using CoO NWs as catalyst. The response (resistance ratio) of the Co-doped branched ZnO NW network sensor to 5 ppm <i>p</i>-xylene at 400 °C was 19.55, which was significantly higher than those to 5 ppm toluene, C₂H₅OH, and other interference gases. The sensitive and selective detection of <i>p</i>-xylene, particularly distinguishing among benzene, toluene, and xylene with lower cross-responses to C₂H₅OH, can be attributed to the tuned catalytic activity of Co components, which induces preferential dissociation of <i>p</i>-xylene into more active species, as well as the increase of chemiresistive variation due to the abundant formation of Schottky barriers between the branches

Ionic block copolymer doped reduced graphene oxide supports with ultra-fine Pd nanoparticles: strategic realization of ultra-accelerated nanocatalysis

We synthesized an ultra-fine Pd nanocatalyst supported by ionic block copolymer doped reduced graphene oxide (Pd-PIBrGO) for ultra-accelerated nanocatalysis. This hybrid catalyst exhibited exceptionally advanced catalytic performance for the reduction of methylene blue using miniscule quantities of Pd-PIBrGO due to facilitated diffusion of reagents, resulting in full reduction within a few seconds and showing a 280-fold increase of the rate constant over Pd-rGO without ionic block copolymers

Effect of Early Management on Pain and Depression in Patients with Pancreatobiliary Cancer: A Randomized Clinical Trial

Background: The present study assessed whether early palliative care (EPC) targeting pain and depression and automated symptom monitoring could improve symptoms in patients with advanced pancreatobiliary cancer. Methods: Patients diagnosed with pathologically confirmed locally advanced or metastatic pancreatic or biliary tract cancer who had cancer-related pain (brief pain inventory (BPI) worst pain score &gt;3) and/or depression (Center for Epidemiological Studies&mdash;Depression Scale (CES-D) &gt;16) were randomized within 8 weeks after diagnosis to receive EPC or on-demand palliative care (n = 144 each). EPC included (1) nursing assessment of pain and depression, (2) pain control based on National Comprehensive Cancer Network guidelines, (3) depression control by psychoeducation and/or consultation with a psychiatric specialist, and (4) patient education. The primary end points were &ge;50% reductions from baseline to week 4 in pain and depression scores. Results: The proportion of patients in the EPC and usual care groups with &ge;50% reductions in pain (29.5% vs. 25.2%; p = 0.4194) and depression (30.8% vs. 36.8%; p = 0.5732) scores from baseline to week 4 did not differ significantly. The proportion of patients with BPI worst pain score &le;3 was significantly higher (51.1% vs. 38.9%, p = 0.0404) and the reduction in pain intensity score significantly greater (1.5 vs. 1.0 points, p = 0.0318) in the EPC than in the usual care group. At 4 weeks, patients in the EPC group reported significant increases in global health status, role of functioning, nausea and vomiting, and pain scores on the European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) general questionnaire. Conclusions: Although the primary outcome was not met, this trial indicates that EPC may improve early pain relief in patients with advanced pancreatobiliary cancers

Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes.

Glycated hemoglobin (HbA1c) is an indicator of the average blood glucose concentration. Failing to control HbA1c levels can accelerate the development of complications in patients with diabetes. Although metabolite profiles associated with HbA1c level in diabetes patients have been characterized using different platforms, more studies using high-throughput technology will be helpful to identify additional metabolites related to diabetes. Type 2 diabetes (T2D) patients were divided into two groups based on the HbA1c level: normal (HbA1c ≤6%) and high (HbA1c ≥9%) in both discovery and replication sets. A targeted metabolomics approach was used to quantify serum metabolites and multivariate logistic regression was used to identify significant differences between groups. The concentrations of 22 metabolites differed significantly between the two groups in the discovery set. In the replication set, the levels of 21 metabolites, including 16 metabolites identified in the discovery set, differed between groups. Among these, concentrations of eleven amino acids and one phosphatidylcholine (PC), lysoPC a C16:1, were higher and four metabolites, including three PCs (PC ae C36:1, PC aa C26:0, PC aa C34:2) and hexose, were lower in the group with normal HbA1c group than in the group with high HbA1c. Metabolites with high concentrations in the normal HbA1c group, such as glycine, valine, and PCs, may contribute to reducing HbA1c levels in patients with T2D. The metabolite signatures identified in this study provide insight into the mechanisms underlying changes in HbA1c levels in T2D