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dna microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?

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EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 2016年第8期35卷 1285-1295页

作者： Blomfeldt, A. Aamot, H. V. Eskesen, A. N. Monecke, S. White, R. A. Leegaard, T. M. Bjornholt, J. V. Akershus Univ Hosp Dept Microbiol & Infect Control Lorenskog Norway Akershus Univ Hosp Dept Clin Mol Biol EpiGen Lorenskog Norway Univ Oslo Lorenskog Norway Akershus Univ Hosp Dept Infect Dis Lorenskog Norway Alere Technol GmbH Jena Germany Tech Univ Dresden Inst Med Microbiol & Hyg Dresden Germany Norwegian Inst Publ Hlth Dept Infect Dis Epidemiol Oslo Norway Univ Oslo Inst Clin Med Oslo Norway

Providing evidence for microbial genetic determinants' impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe-host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by dna microarray analysis and spa typing. Fisher's exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by dna microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing.

关键词： Sulfur Staphylococcus aureus alachlor dna microarray analysis Mortality Infection of bloodstream Isolates bacterial gene PLK4 gene

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Estimating the number of equal components for two high-dimensional mean vectors

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COMMUNICATIONS IN STATISTICS-THEORY AND METHODS 2021年第19期50卷 4617-4638页

作者： Yu, Wei Xu, Wangli Zhu, Lixing Anhui Univ Sch Math Sci Hefei Peoples R China Renmin Univ China Sch Stat Ctr Appl Stat Beijing Peoples R China Beijing Normal Univ Sch Stat Beijing 100875 Peoples R China Hong Kong Baptist Univ Dept Math Hong Kong Peoples R China North West Univ Unit Business Math & Informat Potchefstroom South Africa

In this article, we propose a new method for estimating the number of equal components m(0) of two m-dimensional population means when m is large. The proposed method can be used to estimate the number of equally expressed or differentially expressed genes in dna microarray studies. It can also be applied in the step of estimating m(0) in adaptive false discovery rate controlling procedures. Simulation results show that the bias of the moment estimator is very small for both normal and non normal data. It has higher precision than existing methods in most cases. It has more evident advantage under non normal data.

关键词： Multiple hypothesis testing high-dimensional data dna microarray analysis false discovery rate

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Transcriptomic analysis of HepG2 cells exposed to fractionated wastewater effluents suggested humic substances as potential inducer of whole effluent toxicity

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CHEMOSPHERE 2020年 240卷 124894-000页

作者： Hara-Yamamura, Hiroe Fukushima, Toshikazu Tan, Lea Chua Okabe, Satoshi Hokkaido Univ Fac Engn Div Environm Engn Kita Ku Kita 13Nishi 8 Sapporo Hokkaido 0608628 Japan Kanazawa Univ Inst Sci & Engn Fac Geosci & Civil Engn Kakumamachi Kanazawa Ishikawa 9201192 Japan Nippon Steel Corp Ltd Adv Technol Res Labs Environm Res Lab 20-1 Shintomi Futtsu Chiba 2938511 Japan Natl Univ Ireland Dept Microbiol Galway Room122 Orbsen BldgUniv Rd Galway H91 TK33 Ireland

We performed a transcriptome-based bioassay (TSB assay) using human hepatoma HepG2 cells to evaluate the potential toxicity of whole wastewater effluents from two membrane bioreactors (MBRs) and a conventional activated sludge process (AS). The biologically active agent(s) in the wastewater effluents were characterized based on expression of the marker genes (i.e., CYP1A1, AKR1B10, GCLM and GPX2) selected by dna microarray analysis, after the wastewater effluent samples were concentrated by a reverse osmosis (RO) membrane and further fractionated by various manipulations. The qPCR assay of marker genes demonstrated that the induction of CYP1A1 and GPX2 was mitigated after passing through 08 and chelate columns. In addition, clear induction of CYP1A1 was observed in the smallest size fraction with 1 k Da or smaller organic molecules in all the tested effluents. These results together with the water quality data of the fractionated samples suggested that responsible constituents for potentially adverse and abnormal transcriptomic responses in HepG2 could have hydrophobic nature and act with metal-dissolved organic matter (DOM) complexes in 1 k Da or smaller size fraction. Although DOM is known to play two contradictory roles as a protector and an inducer of toxicants, our present study indicated the DOM in wastewater effluent, particularly humic substances with acidic nature, functioned as a toxicity inducer of residual chemicals in the effluents. This study provided a new insight into the nature of "toxic unknowns" in the wastewater effluents, which should be monitored whole through the reclamation process and prioritized for removal. (C) 2019 Elsevier Ltd. All rights reserved.

关键词： Transcriptome-based bioassay dna microarray analysis Marker genes Whole effluent toxicity Reverse osmosis Water treatment

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Survey of Staphylococcus aureus carriage by free-living red deer (Cervus elaphus): Evidence of human and domestic animal lineages

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TRANSBOUNDARY AND EMERGING DISEASES 2022年第5期69卷 E1659-E1669页

作者： Luzzago, Camilla Lauzi, Stefania Ehricht, Ralf Monecke, Stefan Corlatti, Luca Pedrotti, Luca Piccinini, Renata Univ Milan Dept Vet Med Milan Italy Univ Milan Coordinated Res CenterEpiSOMI Milan Italy Leibniz Inst Photon Technol IPHT Jena Germany InfectoGnost Res Campus Jena Germany Friedrich Schiller Univ Inst Phys Chem Jena Germany Dresden Univ Hosp Inst Med Microbiol & Virol Dresden Germany Parco Nazl Stelvio Bormio Italy Univ Freiburg Chair Wildlife Ecol & Management Freiburg Germany

Staphylococcus aureus is a pathogen that can affect multiple host species. Evidence of transmission between humans and animals and among different animal species has been reported in recent years. In this study, we investigated 284 free-living red deer (Cervus elaphus) in the Central Italian Alps to assess the prevalence and molecular characteristics of S. aureus in nasal and intestinal samples in relation to host features and environmental factors. A prevalence of 90%, 26.2% and 10.7% of S. aureus was detected in nasal rectal swabs and faeces, respectively. Calves had a higher probability of being S. aureus intestinal carriers than adults, especially in females when considering faecal samples. Clonal complex (CC) 425 was the most prevalent lineage (61.5%). This is a lineage known to be widespread in both domestic and free-living animals. It was followed by CC2671 (15.4%) and CC350 (6.4%). A high rate of the phage-borne virulence factor lukM/lukF-P83 was detected in CC425 and CC350. Further lineages, which are known to occur in both humans and animals, were detected sporadically in red deer faeces only, that is, CC7, CC9, CC121 and CC707, harbouring the genes of the penicillinase operon and a gene for macrolide resistance (CC9 and CC121). Methicillin resistance genes mecA and mecC were not found. Our results suggest that free-living red deer may be reservoir for S. aureus in Alpine habitats.

关键词： cervidae dna microarray analysis multi-host pathogen red deer Staphylococcus aureus wildlife

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Multiple protein and mRNA expression correlations in the rat cerebral cortex after ischemic injury and repair due to buchang naoxintong jiaonang (BNJ) intervention

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BIOMEDICINE & PHARMACOTHERAPY 2020年第0期125卷 109917-000页

作者： Liu, Xin Wang, Qing Cui, Yiran Hussain, Muhammad Yang, Hongjun Li, Xianyu Beijing Univ Chinese Med Sch Chinese Mat Med Beijing 100029 Peoples R China Beijing Univ Chinese Med Sch Life Sci Beijing 100029 Peoples R China Capital Med Univ Beijing Hosp Tradit Chinese Med Beijing 100010 Peoples R China Univ Sci & Technol Beijing Sch Chem & Biol Engn Beijing 100083 Peoples R China China Acad Chinese Med Sci Inst Chinese Mat Med Beijing 100700 Peoples R China China Acad Chinese Med Sci Beijing Key Lab Tradit Chinese Med Basic Res Prev Expt Res Ctr Beijing 100700 Peoples R China

Stroke is the one of the most common causes of death worldwide. Systematic description and characterization of the types of stroke and the effects induced in the cerebral cortex have not been performed so far. Here, we analyzed the protein and mRNA expression in the cerebral cortex12 h after ischemic injury and repair. Drug intervention using Buchang Naoxintong Jiaonang (BNJ), which has been reported to have good clinical therapeutic effects, was selected for our study of cerebral ischemic repair in rat models. Two powerful techniques can be merged in a single study to examine and yield new perspectives in physiology and pathophysiology. Combining LC-MS/MS and dna microarray analyses of the rat cerebral cortex confidently identified two large datasets in more than three biological replicates. Quantitative approaches were then used to quantify the differences among the four experimental groups the naive, sham, middle cerebral artery occlusion MCAO and MCAO + BNJ groups by a label-free proteomics approach and a Cy5-labeled microarray approach. In brief, 3217 unique proteins and 24,300 unique gene symbols were confidently identified. Bioinformatics analysis revealed that of these unique proteins and gene symbols, 269 proteins and 632 gene symbols were identified to be differentially expressed. The results of subcellular localization, hierarchical clustering, and pathway enrichment analyses were combined with the results of the injury and repair phase analyses, and twelve proteins and twenty-seven gene symbols were significantly differentially expressed and were identified as potential candidates for cerebral ischemic injury involvement;all the candidates were verified by western blot and quantitative real-time PCR analysis. The primary enriched MAPK signaling pathway may play a key role in the molecular mechanisms related to cerebral ischemic injury. The observations of the present study help to illuminate the regulatory mechanism of cerebral ischemic injury and repair

关键词： Cerebral cortex Ischemic injury Proteomic analysis dna microarray analysis Buchang naoxintong jiaonang (BNJ)

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Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD

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MODERN RHEUMATOLOGY 2020年第3期30卷 551-557页

作者： Nakamura, Takuji Satoh-Nakamura, Tomomi Nakajima, Akio Kawanami, Takafumi Sakai, Tomoyuki Fujita, Yoshimasa Iwao, Haruka Miki, Miyuki Masaki, Yasufumi Okazaki, Toshiro Ishigaki, Yasuhito Kawano, Mitsuhiro Yamada, Kazunori Matsui, Shoko Saeki, Takako Kamisawa, Terumi Yamamoto, Motohisa Hamano, Hideaki Origuchi, Tomoki Hirata, Shintaro Tanaka, Yoshiya Tsuboi, Hiroto Sumida, Takayuki Okazaki, Kazuichi Tanaka, Masao Chiba, Tsutomu Mimori, Tsuneyo Umehara, Hisanori Nagahama City Hosp Dept Rheumatol & Immunol Shiga Japan Kanazawa Med Univ Hematol & Immunol Uchinada Ishikawa Japan Kudo Gen Hosp Div Rheumatol Kaga Ishikawa Japan Kanazawa Med Univ Med Res Inst Uchinada Ishikawa Japan Kanazawa Univ Hosp Dept Internal Med Div Rheumatol Kanazawa Ishikawa Japan Univ Toyama Hlth Adm Ctr Toyama Japan Nagaoka Red Cross Hosp Dept Internal Med Niigata Japan Tokyo Metropolitan Komagome Hosp Dept Internal Med Tokyo Japan Sapporo Med Univ Sch Med Dept Rheumatol Sapporo Hokkaido Japan Shinshu Univ Sch Hosp Med Informat Div Nagano Japan Shinshu Univ Sch Hosp Dept Internal Med Gastroenterol Nagano Japan Nagasaki Grad Sch Hlth Sci Dept Immunol & Rheumatol Dept Internal Med 1 Nagasaki Japan Univ Occupat & Environm Hlth Sch Med Dept Internal Med 1 Fukuoka Fukuoka Japan Hiroshima Univ Hosp Dept Clin Immunol & Rheumatol Hiroshima Japan Univ Tsukuba Fac Med Dept Internal Med Ibaraki Japan Kansai Med Univ Div Gastroenterol & Hepatol Dept Internal Med 3 Osaka Japan Kyoto Univ Grad Sch Med Dept Clin Immunol Kyoto Japan Kyoto Univ Fac Med Kyoto Japan Kyoto Univ Grad Sch Med Dept Gastroenterol & Hepatol Kyoto Japan

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD. Method: dna microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals. Result: dna microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment. Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.

关键词： IgG4-related disease dna microarray analysis innate immunity related gene innate immunity acquired immunity

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Linderapyrone: A Wnt signal inhibitor isolated from Lindera umbellata

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2021年 45卷 128161-128161页

作者： Matsumoto, Takahiro Kitagawa, Takahiro Imahori, Daisuke Matsuzaki, Atsushi Saito, Youhei Ohta, Tomoe Yoshida, Tatsusada Nakayama, Yuji Ashihara, Eishi Watanabe, Tetsushi Kyoto Pharmaceut Univ Yamashinaku Kyoto 6078414 Japan Nagasaki Int Univ Nagasaki 8593298 Japan

Linderapyrone, a Wnt signal inhibitor was isolated from the methanolic extract of the stems and twigs of Lindera umbellata together with epi-(-)-linderol A. Linderapyrone inhibited TCF/beta-catenin transcriptional activity that was evaluated using cell-based TOPFlash luciferase assay system. To evaluate the structure-activity relationship and mechanism, we synthesized linderapyrone and its derivatives from piperitone. As the results of further bioassay for synthesized compounds, we found both of pyrone and monoterpene moieties were necessary for inhibitory effect. cdna microarray analysis in a linderapyrone derivative treated human colorectal cancer cells showed that this compound downregulates Wnt signaling pathway. Moreover, we successes to synthesize the derivative of linderapyrone that has stronger inhibitory effect than linderapyrone and ICG-001 (positive control).

关键词： Linderapyrone Lindera umbellata Wnt signal TCF/beta-catenin transcriptional activity dna microarray analysis

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Classification of a dna microarray for Diagnosing Cancer Using a Complex Network Based Method

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IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2019年第3期16卷 801-808页

作者： Wu, Peng Wang, Dong Univ Jinan Sch Informat Sci & Engn Jinan 250022 Shandong Peoples R China Qinghai Normal Univ Key Lab Med Plant & Anim Resources Qinghai Tibet Xining 810008 Qinghai Peoples R China

Applications that classify dna microarray expression data are helpful for diagnosing cancer. Many attempts have been made to analyze these data;however, new methods are needed to obtain better results. In this study, a Complex Network (CN) classifier was exploited to implement the classification task. An algorithm was used to initialize the structure, which allowed input variables to be selected over layered connections and different activation functions for different nodes. Then, a hybrid method integrated the Genetic Programming and the Particle Swarm Optimization algorithms was used to identify an optimal structure with the parameters encoded in the classifier. The single CN classifier and an ensemble of CN classifiers were tested on four bench data sets. To ensure diversity of the ensemble classifiers, we constructed a base classifier using different feature sets, i.e., Pearson's correlation, Spearman's correlation, euclidean distance, Cosine coefficient, and the Fisher-ratio. The experimental results suggest that a single classifier can be used to obtain state-of-the-art results and the ensemble yielded better results.

关键词： Cancer diagnosis classification complex networks dna microarray analysis ensemble classifier gene selection

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Exostosin 1 is expressed in human odontoblasts

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ARCHIVES OF ORAL BIOLOGY 2017年 80卷 175-179页

作者： Paakkonen, Virve Saraniemi, Stina Bleicher, Francoise Nevo, Zvi Tjaderhane, Leo Univ Oulu Res Unit Oral Hlth Sci POB 5281 FIN-90014 Oulu Finland Inst Genom Fonct F-69007 Lyon France Univ Lyon F-69000 Lyon France Tel Aviv Univ Dept Human Mol Genet & Biochem Sackler Sch Med Tel Aviv Israel Oulu Univ Hosp Med Res Ctr Oulu MRC Oulu Oulu Finland Univ Helsinki Dept Oral & Maxillofacial Dis Helsinki Finland Helsinki Univ Hosp Helsinki Finland

Objective: Dental pulp is soft connective tissue maintaining the vitality of the tooth, while odontoblasts form the dentin. Our earlier dna microarray analysis revealed expression of putative tumour suppressor exostosin 1 (EXT-1) in odontoblasts. EXT-1 is essential for heparan sulphate synthesis, which may play a role in the dentin mineralization. Since the absence of the functional EXT-1 causes bone tumours, expression in odontoblasts is interesting. Our aim was to analyse further the EXT-1 expression in human tooth. Designs: dna microarray and PCR techniques were used to study the EXT-1 expression in mature native human odontoblasts and pulp tissue as well as in newly-differentiated cultured odontoblast-like cells. Immunohistochemistry was performed to study EXT-1 protein in mature human teeth, teeth with incomplete root and developing teeth. Results: Markedly higher EXT-1 was observed in mature odontoblasts than in pulp at mRNA level with dna microarray and PCR techniques. Immunohistochemistry of mature tooth revealed EXT-1 both in odontoblasts and the predentin but not in the dentin. EXT-1 was also observed in the odontoblasts of incomplete root, but the localization of the staining was different. In developing foetal tooth, staining was detected in ameloblasts and the basal lamina. Conclusions: The detection of EXT-1 in both mature and newly-differentiated cells indicates a role in the odontoblast function, and EXT-1 staining in the predentin indicates a function in the dentin formation. Detection of EXT-1 in developing teeth indicates a role in tooth development.

关键词： Odontoblasts dna microarray analysis Viability Dentin HUMAN TOOTH Tooth

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CD26/DPPIV inhibition alters the expression of immune response-related genes in the thymi of NOD mice

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MOLECULAR AND CELLULAR ENDOCRINOLOGY 2016年第C期426卷 101-112页

作者： Teresa Julian, Maria Alonso, Nuria Colobran, Roger Sanchez, Alex Minarro, Antoni Pujol-Autonell, Irma Carrascal, Jorge Rodriguez-Fernandez, Silvia Maria Ampudia, Rosa Vives-Pi, Marta Puig-Domingo, Manel Germans Trias & Pujol Hlth Sci Res Inst & Hosp Dept Endocrinol & Nutr Badalona 08916 Spain Autonomous Univ Barcelona E-08193 Barcelona Spain Vall dHebron Univ Hosp VHIR Div Immunol Barcelona 08035 Spain Autonomous Univ Barcelona Germans Trias & Pujol Hlth Sci Res Inst & Hosp Dept Immunol Badalona 08916 Spain Univ Barcelona Fac Biol Dept Stat E-08028 Barcelona Spain VHIR Stat & Bioinformat Unit Barcelona 08035 Spain Inst Salud Carlos III CIBER Diabet & Associated Metab Dis CIBERDEM Madrid 28029 Spain Inst Salud Carlos III CIBER Rare Dis CIBERER Madrid 28029 Spain

The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new-onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the specific mechanisms involved in these effects remain unknown. The aim of the present study was to investigate how DPPIV inhibition modifies the expression of genes in the thymus of NOD mice by microarray analysis. Changes in the gene expression of beta-cell autoantigens and Aire in thymic epithelial cells (TECs) were also evaluated by using qRT-PCR. A DPPIV inhibitor, MK626, was orally administered in the diet for 4 and 6 weeks starting at 6-8 weeks of age. Thymic glands from treated and control mice were obtained for each study checkpoint. Thymus transcriptome analysis revealed that 58 genes were significantly over-expressed in MK626-treated mice after 6 weeks of treatment. Changes in gene expression in the thymus were confined mainly to the immune system, including innate immunity, chemotaxis, antigen presentation and immunoregulation. Most of the genes are implicated in central tolerance mechanisms through several pathways. No differences were observed in the expression of Aire and beta-cell autoantigens in TECs. In the current study, we demonstrate that treatment with the DPPIV inhibitor MK626 in NOD mice alters the expression of the immune response-related genes in the thymus, especially those related to immunological central tolerance, and may contribute to the prevention of T1D. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

关键词： Type 1 diabetes prevention DPPIV/CD26 inhibition dna microarray analysis beta-cell autoantigens expression NOD mice Gene expression

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