bluuebunny/crossref_metadata_2025_split huggingface dataset:
MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer
Authors: Helwa Reham , Gansmo Liv B. , Romundstad Pål , Hveem Kristian , Vatten Lars , Ryan Bríd M. , Harris Curtis C. , Lønning Per E. , Knappskog Stian 
Published: September 2016

AbstractTwo functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01–1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00–1.45) and among females (OR = 1.32; 95% CI = 1.01–1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00–1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009).
Panel-Based Population Next-Generation Sequencing for Inherited Retinal Degenerations
Authors: Carrigan Matthew , Duignan Emma , Malone Conor P. G. , Stephenson Kirk , Saad Tahira , McDermott Ciara , Green Andrew , Keegan David , Humphries Peter , Kenna Paul F. , Farrar G. Jane 
Published: September 2016

AbstractInherited retinopathies affect approximately two and a half million people globally, yet the majority of affected patients lack clear genetic diagnoses given the diverse range of genes and mutations implicated in these conditions. We present results from a next-generation sequencing study of a large inherited retinal disease patient population, with the goal of providing clear and actionable genetic diagnoses. Targeted sequencing was performed on 539 individuals from 309 inherited retinal disease pedigrees. Causative mutations were identified in the majority (57%, 176/309) of pedigrees. We report the association of many previously unreported variants with retinal disease, as well as new disease phenotypes associated with known genes, including the first association of the SLC24A1 gene with retinitis pigmentosa. Population statistics reporting the genes most commonly implicated in retinal disease in the cohort are presented, as are some diagnostic conundrums that can arise during such studies. Inherited retinal diseases represent an exemplar group of disorders for the application of panel-based next-generation sequencing as an effective tool for detection of causative mutations.
Double-layered cell transfer technology for bone regeneration
Authors: Akazawa Keiko , Iwasaki Kengo , Nagata Mizuki , Yokoyama Naoki , Ayame Hirohito , Yamaki Kazumasa , Tanaka Yuichi , Honda Izumi , Morioka Chikako , Kimura Tsuyoshi , Komaki Motohiro , Kishida Akio , Izumi Yuichi , Morita Ikuo 
Published: September 2016

AbstractFor cell-based medicine, to mimic in vivo cellular localization, various tissue engineering approaches have been studied to obtain a desirable arrangement of cells on scaffold materials. We have developed a novel method of cell manipulation called “cell transfer technology”, enabling the transfer of cultured cells onto scaffold materials, and controlling cell topology. Here we show that using this technique, two different cell types can be transferred onto a scaffold surface as stable double layers or in patterned arrangements. Various combinations of adherent cells were transferred to a scaffold, amniotic membrane, in overlapping bilayers (double-layered cell transfer), and transferred cells showed stability upon deformations of the material including folding and trimming. Transplantation of mesenchymal stem cells from periodontal ligaments (PDLSC) and osteoblasts, using double-layered cell transfer significantly enhanced bone formation, when compared to single cell type transplantation. Our findings suggest that this double-layer cell transfer is useful to produce a cell transplantation material that can bear two cell layers. Moreover, the transplantation of an amniotic membrane with PDLSCs/osteoblasts by cell transfer technology has therapeutic potential for bone defects. We conclude that cell transfer technology provides a novel and unique cell transplantation method for bone regeneration.
Species characteristics of lead in sea foods collected from coastal water of Fujian, Southeastern of China
Authors: He Ye , Chen Zhiqiang , Mo Fan , Huang Limei , Xu LiangJun , Wu Yongning , Xue Zhimin , Fu FengFu 
Published: September 2016

AbstractVarious sea foods including fish, shellfish and shrimp were collected from different coastal areas of Fujian in China, and their Pb species characteristics were investigated in detail. The results indicated that there are two different species characteristics of Pb existing in sea food samples. About half of samples were detected to have only Pb2+, and another half of samples were detected to have both Pb2+ and trimethyl lead (TML). The results also revealed that Pb species characteristics in the sea foods rather depend on the species of sea food than the sampling area. In comparison with shellfish/shrimp samples, fish samples have higher concentrations of TML and Pb2+. Especially, the average concentration of TML in the TML-detected fish samples is about 3 times of that in the TML-detected shellfish/shrimp samples, indicating that fish has stronger ability to uptake and accumulate TML. The concentrations of total lead in all samples are lower than the maximum allowable limit of national standard, suggesting that the sea foods collected from Fujian are safe for consumption. By considering that TAL has more toxicity than Pb2+, the effect of TML in sea foods on the human health should be paid more attention in the future.
Contamination-controlled high-throughput whole genome sequencing for influenza A viruses using the MiSeq sequencer
Authors: Lee Hong Kai , Lee Chun Kiat , Tang Julian Wei-Tze , Loh Tze Ping , Koay Evelyn Siew-Chuan 
Published: September 2016

AbstractAccurate full-length genomic sequences are important for viral phylogenetic studies. We developed a targeted high-throughput whole genome sequencing (HT-WGS) method for influenza A viruses, which utilized an enzymatic cleavage-based approach, the Nextera XT DNA library preparation kit, for library preparation. The entire library preparation workflow was adapted for the Sentosa SX101, a liquid handling platform, to automate this labor-intensive step. As the enzymatic cleavage-based approach generates low coverage reads at both ends of the cleaved products, we corrected this loss of sequencing coverage at the termini by introducing modified primers during the targeted amplification step to generate full-length influenza A sequences with even coverage across the whole genome. Another challenge of targeted HTS is the risk of specimen-to-specimen cross-contamination during the library preparation step that results in the calling of false-positive minority variants. We included an in-run, negative system control to capture contamination reads that may be generated during the liquid handling procedures. The upper limits of 99.99% prediction intervals of the contamination rate were adopted as cut-off values of contamination reads. Here, 148 influenza A/H3N2 samples were sequenced using the HTS protocol and were compared against a Sanger-based sequencing method. Our data showed that the rate of specimen-to-specimen cross-contamination was highly significant in HTS.
A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy
Authors: Oka Tetsuo , Kurozumi Kazuhiko , Shimazu Yosuke , Ichikawa Tomotsugu , Ishida Joji , Otani Yoshihiro , Shimizu Toshihiko , Tomita Yusuke , Sakaguchi Masakiyo , Watanabe Masami , Nasu Yasutomo , Kumon Hiromi , Date Isao 
Published: September 2016

AbstractReduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87ΔEGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10. Cytotoxicity assays showed that Ad-SGE-REIC resulted in a time-dependent and significant reduction in the number of malignant glioma cells attaching to the bottom of culture wells. Xenograft and syngeneic mouse intracranial glioma models treated with Ad-SGE-REIC had significantly longer survival than those treated with the control vector Ad-LacZ or with Ad-CAG-REIC. This study demonstrated the anti-glioma effect of Ad-SGE-REIC, which may represent a promising strategy for the treatment of malignant glioma.
Thiol dependent intramolecular locking of Orai1 channels
Authors: Alansary Dalia , Schmidt Barbara , Dörr Kathrin , Bogeski Ivan , Rieger Heiko , Kless Achim , Niemeyer Barbara A. 
Published: September 2016

AbstractStore-operated Ca2+ entry mediated by STIM1-gated Orai1 channels is essential to activate immune cells and its inhibition or gain-of-function can lead to immune dysfunction and other pathologies. Reactive oxygen species interacting with cysteine residues can alter protein function. Pretreatment of the Ca2+ selective Orai1 with the oxidant H2O2 reduces ICRAC with C195, distant to the pore, being its major redox sensor. However, the mechanism of inhibition remained elusive. Here we combine experimental and theoretical approaches and show that oxidation of Orai1 leads to reduced subunit interaction, slows diffusion and that either oxidized C195 or its oxidomimetic mutation C195D located at the exit of transmembrane helix 3 virtually eliminates channel activation by intramolecular interaction with S239 of transmembrane helix 4, thereby locking the channel in a closed conformation. Our results demonstrate a novel mechanistic model for ROS-mediated inhibition of Orai1 and identify a candidate residue for pharmaceutical intervention.
An Intronless β-amyrin Synthase Gene is More Efficient in Oleanolic Acid Accumulation than its Paralog in Gentiana straminea
Authors: Liu Yanling , Zhao Zhongjuan , Xue Zheyong , Wang Long , Cai Yunfei , Wang Peng , Wei Tiandi , Gong Jing , Liu Zhenhua , Li Juan , Li Shuo , Xiang Fengning 
Published: September 2016

AbstractParalogous members of the oxidosqualene cyclase (OSC) family encode a diversity of enzymes that are important in triterpenoid biosynthesis. This report describes the isolation of the Gentiana straminea gene GsAS2 that encodes a β-amyrin synthase (βAS) enzyme. Unlike its previously isolated paralog GsAS1, GsAS2 lacks introns. Its predicted protein product was is a 759 residue polypeptide that shares high homology with other known β-amyrin synthases (βASs). Heterologously expressed GsAS2 generates more β-amyrin in yeast than does GsAS1. Constitutive over-expression of GsAS2 resulted in a 5.7 fold increase in oleanolic acid accumulation, while over-expression of GsAS1 led to a 3 fold increase. Additionally, RNAi-directed suppression of GsAS2 and GsAS1 in G. straminea decreased oleonolic acid levels by 65.9% and 21% respectively, indicating that GsAS2 plays a more important role than GsAS1 in oleanolic acid biosynthesis in G. straminea. We uses a docking model to explore the catalytic mechanism of GsAS1/2 and predicted that GsAS2, with its Y560, have higher efficiency than GsAS1 and mutated versions of GsAS2 in β-amyrin produce. When the key residue in GsAS2 was mutagenized, it produced about 41.29% and 71.15% less β-amyrin than native, while the key residue in GsAS1 was mutagenized to that in GsAS2, the mutant produced 38.02% more β-amyrin than native GsAS1.
ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons
Authors: Liu Zhiying , Zang Yunjin , Qiao Luxin , Liu Kai , Ouyang Yabo , Zhang Yulin , Chen Dexi 
Published: September 2016

AbstractThe mechanisms behind HIV-1-associated neurocognitive disorders are still unclear. Apoptosis-stimulating protein 2 of p53 (ASPP2) is a damage-inducible p53-binding protein that stimulates p53-mediated apoptosis and transactivates proapoptotic and cell cycle regulatory genes. It has been reported that ASPP2 has a specific regulatory function in the death of retinal ganglion cells and the development of Alzheimer’s disease. In this study, we used p53 and ASPP2 knockout mice and primary cerebrocortical neuron culture to analyze the role of the interaction between ASPP2 with p53 in HIV-1 envelope glycoprotein gp120-induced neurotoxicity. The results showed that 10 ng/mL gp120 protein might stimulate p53 overexpression and translocation to the nucleus, and 30 ng/mL gp120 protein could stimulate both p53 and ASPP2 translocation to the nucleus, but only with p53 overexpression. The primary cultured neurons of p53−/−ASPP2+/− mice had a higher survival rate than p53−/− mice under gp120 protein stress. The interaction of ASPP2 with p53 induced by a high dose of gp120 stimulated Bax transcription and contributed to caspase-3 cleavage, and ASPP2-siRNA attenuated gp120 induced neuron death through inhibition of Bax expression. These results suggest that ASPP2 plays an important role in p53-mediated neuronal apoptosis under gp120 stress.
The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus
Authors: Hillmann Falk , Bagramyan Karine , Straßburger Maria , Heinekamp Thorsten , Hong Teresa B. , Bzymek Krzysztof P. , Williams John C. , Brakhage Axel A. , Kalkum Markus 
Published: September 2016

AbstractInvasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3’s peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.
Robust entanglement between a movable mirror and atomic ensemble and entanglement transfer in coupled optomechanical system
Authors: Bai Cheng-Hua , Wang Dong-Yang , Wang Hong-Fu , Zhu Ai-Dong , Zhang Shou 
Published: September 2016

AbstractWe propose a scheme for the creation of robust entanglement between a movable mirror and atomic ensemble at the macroscopic level in coupled optomechanical system. We numerically simulate the degree of entanglement of the bipartite macroscopic entanglement and show that it depends on the coupling strength between the cavities and is robust with respect to the certain environment temperature. Inspiringly and surprisingly, according to the reported relation between the mechanical damping rate and the mechanical frequency of the movable mirror, the numerical simulation result shows that such bipartite macroscopic entanglement persists for environment temperature up to 170 K, which breaks the liquid nitrogen cooling and liquid helium cooling and largely lowers down the experiment cost. We also investigate the entanglement transfer based on this coupled system. The scheme can be used for the realization of quantum memories for continuous variable quantum information processing and quantum-limited displacement measurements.
Visible-absorption spectroscopy as a biomarker to predict treatment response and prognosis of surgically resected esophageal cancer
Authors: Yang Pei-Wen , Hsu I-Jen , Chang Chun-Wei , Wang Yu-Chia , Hsieh Ching-Yueh , Shih Kuan-Hui , Wong Li-Fan , Shih Nai-Yu , Hsieh Min-Shu , Hou Max Ti-Kuang , Lee Jang-Ming 
Published: September 2016

AbstractThe application of optical absorption spectra in prognostic prediction has hardly been investigated. We developed and evaluated a novel two dimensional absorption spectrum measurement system (TDAS) for use in early diagnosis, evaluating response to chemoradiation, and making prognostic prediction. The absorption spectra of 120 sets of normal and tumor tissues from esophageal cancer patients were analyzed with TDAS ex-vivo. We demonstrated the cancerous tissue, the tissue from patients with a poor concurrent chemoradiotherapy (CCRT) response, and the tissue from patients with an early disease progression each had a readily identifiable common spectral signature. Principal component analysis (PCA) classified tissue spectra into distinct groups, demonstrating the feasibility of using absorption spectra in differentiating normal and tumor tissues, and in predicting CCRT response, poor survival and tumor recurrence (efficiencies of 75%, 100% and 85.7% respectively). Multivariate analysis revealed that patients identified as having poor-response, poor-survival and recurrence spectral signatures were correlated with increased risk of poor response to CCRT (P = 0.012), increased risk of death (P = 0.111) and increased risk of recurrence (P = 0.030) respectively. Our findings suggest that optical absorption microscopy has great potential to be a useful tool for pre-operative diagnosis and prognostic prediction of esophageal cancer.
High-throughput sequencing-based analysis of endogenetic fungal communities inhabiting the Chinese Cordyceps reveals unexpectedly high fungal diversity
Authors: Xia Fei , Chen Xin , Guo Meng-Yuan , Bai Xiao-Hui , Liu Yan , Shen Guang-Rong , Li Yu-Ling , Lin Juan , Zhou Xuan-Wei 
Published: September 2016

AbstractChinese Cordyceps, known in Chinese as “DongChong XiaCao”, is a parasitic complex of a fungus (Ophiocordyceps sinensis) and a caterpillar. The current study explored the endogenetic fungal communities inhabiting Chinese Cordyceps. Samples were collected from five different geographical regions of Qinghai and Tibet, and the nuclear ribosomal internal transcribed spacer-1 sequences from each sample were obtained using Illumina high-throughput sequencing. The results showed that Ascomycota was the dominant fungal phylum in Chinese Cordyceps and its soil microhabitat from different sampling regions. Among the Ascomycota, 65 genera were identified, and the abundant operational taxonomic units showed the strongest sequence similarity toOphiocordyceps, Verticillium, Pseudallescheria, CandidaandIlyonectriaNot surprisingly, the genusOphiocordycepswas the largest among the fungal communities identified in the fruiting bodies and external mycelial cortices of Chinese Cordyceps. In addition, fungal communities in the soil microhabitats were clustered separately from the external mycelial cortices and fruiting bodies of Chinese Cordyceps from different sampling regions. There was no significant structural difference in the fungal communities between the fruiting bodies and external mycelial cortices of Chinese Cordyceps. This study revealed an unexpectedly high diversity of fungal communities inhabiting the Chinese Cordyceps and its microhabitats.
GLITTER: a web-based application for gene link inspection through tissue-specific coexpression
Authors: Liu Xiangtao , Yu Pengfei , Cheng Chao , Potash James B. , Han Shizhong 
Published: September 2016

AbstractAccumulating evidence supports the polygenic nature of most complex diseases, suggesting the involvement of many susceptibility genes with small effect sizes. Although hundreds of genes may underlie the genetic architecture of complex diseases, those involved in a given disease are probably not randomly distributed, but likely to be functionally related. Protein-protein interaction networks have been used to evaluate the functional relatedness of susceptibility genes. However, these networks do not account for tissue specificity, are limited to protein-coding genes, and are typically biased by incomplete biological knowledge. Here, we present Gene Link Inspector Through Tissue-specific coExpRession (GLITTER), a web-based application for assessing the functional relatedness of susceptibility genes, either coding or noncoding, according to tissue-specific gene expression profiles. GLITTER can also shed light on the specific tissues in which susceptibility genes might exert their functions. We further demonstrate examples of how GLITTER can evaluate the functional relatedness of susceptibility genes underlying schizophrenia and breast cancer, and provide clues about etiology.
Psychische Krankheit und subjektive Gesundheit bei Wohnungslosen in Zürich
Authors: Briner David , Jäger Matthias , Kawohl Wolfram , Baumgartner-Nietlisbach Gabriela 
Published: September 2016

Zusammenfassung
Anliegen Untersuchung der psychiatrischen Morbidität und der subjektiven Gesundheit (self-rated health, SRH) bei Wohnungslosen in der Stadt Zürich.
Methode Querschnittsstudie bei Wohnungslosen (n = 338) in Zürich und Vergleich der SRH mit jener der Allgemeinbevölkerung (n = 21 597).
Ergebnisse Bei 96 % der Wohnungslosen lag mindestens eine psychiatrische Diagnose vor, am häufigsten Drogen- oder Alkoholabhängigkeit. Wohnungslose bewerteten ihre Gesundheit signifikant schlechter als die Allgemeinbevölkerung.
Schlussfolgerungen Auch in Zürich sind Wohnungslose weit häufiger von psychischer Krankheit betroffen als die Allgemeinbevölkerung. Die SRH ist ein Indikator für die effektive Gesundheit und ist mit der Inanspruchnahme medizinischer Leistungen assoziiert.
Alternative divertor target concepts for next step fusion devices
Authors: Mazul I.V. 
Published: September 2016

Abstract
The operational conditions of a divertor target in the next steps of fusion devices are more severe in comparison with ITER. The current divertor designs and technologies have a limited application concerning these conditions, and so new design concepts/technologies are required. The main reasons which practically prevent the use of the traditional motionless solid divertor target are analyzed. We describe several alternative divertor target concepts in this paper. The comparative analysis of these concepts (including the advantages and the drawbacks) is made and the prospects for their practical implementation are prioritized. The concept of the swept divertor target with a liquid metal interlayer between the moving armour and motionless heat-sink is presented in more detail. The critical issues of this design are listed and outlined, and the possible experiments are presented.