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71.
Bruun-Rasmussen M Madsen CT Jessing S Albrechtsen M 《Molecular plant-microbe interactions : MPMI》2007,20(11):1323-1331
72.
Julie K Laustsen Tue K Rasmussen Kristian Stengaard-Pedersen Kim H?rslev-Petersen Merete L Hetland Mikkel ?stergaard Peter Junker Malene Hvid Bent Deleuran 《Arthritis research & therapy》2014,16(5)
Introduction
OX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA).Methods
Soluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37). Adalimumab was discontinued after the first year, and patients were followed for additional 12 months. For comparison, sOX40 and sOX40L were measured in patients with chronic RA (cRA, n = 15) and healthy volunteers (HV, n = 34). Membrane-bound OX40 and OX40L expression on T cells, B cells and monocytes were quantified.Results
Soluble OX40 plasma levels of eRA patients were not different at the time of treatment initiation, but were significantly higher after 12 months of treatment, compared with HV or cRA patients. Soluble OX40L was significantly elevated throughout the first 12 months of treatment compared with HVs and patients with cRA. Adalimumab treatment did not influence sOX40 or sOX40L plasma levels. At baseline, sOX40L levels were strongly associated with the presence of anti-citrullinated protein antibodies (ACPA) (P <0.001) and IgM-RF (P <0.0001). The sOX40/sOX40L ratio was decreased in eRA, and a low ratio at the time of adalimumab discontinuation was associated with increased DAS28CRP and risk of flare the following year. T cells in the synovial fluid had the highest expression of OX40, while monocytes and B cells were the main expressers of OX40L in the joint.Conclusions
Plasma levels of sOX40 and sOX40L were increased in eRA and sOX40L was correlated with ACPA and IgM-RF. Further, expression of membrane-bound OX40 and OX40L was increased in eRA and cRA. Combined, these findings could reflect that increased activity in the OX40 systems facilitate to drive disease activity and autoantibody production in RA.Trial registration
Clincaltrials.gov , 10 April 2008. NCT00660647Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0474-4) contains supplementary material, which is available to authorized users. 相似文献73.
Background
As a tool to investigate the experiences of six primary emotions, Davis, Panksepp, and Normansell [1] developed the Affective Neuroscience Personality Scales (ANPS). However, the psychometric properties of the ANPS have been questioned, and in particular the factor structure. This study replicates earlier psychometric studies on ANPS in a sample of (546) personality disordered patients, and also includes ANPS-S, a recent short version of ANPS by Pingault and colleagues [2], and a truncated version of BANPS by Barrett and colleagues [3].Methodology/Principal Findings
The study of the full ANPS revealed acceptable internal consistencies of the primary emotion subscales, ranging from 0.74–0.87. However, factor analyses revealed poor to mediocre fit for a six factor solution. Correlational analyses, in addition, revealed too high correlations between PLAY and SEEK, and between SADNESS and FEAR. The two short versions displayed better psychometric properties. The range of internal consistency was 0.61–0.80 for the BANPS scales and 0.65–84 for the ANPS-S. Backward Cronbach Alpha Curves indicated potentials for improvement on all three versions of the questionnaire. Items retained in the short versions did not systematically cover the full theoretical content of the long scales, in particular for CARE and SADNESS in the BANPS. The major problems seem to reside in the operationalization of the CARE and SADNESS subscales of ANPS.Conclusions/Significance
Further work needs to be done in order to realize a psychometrically sound instrument for the assessment of primary emotional experiences. 相似文献74.
Kim Andresen Kirsten Muri Boberg Hege Marie Vedeld Hilde Honne Merete Hektoen Chrisopher A. Wadsworth Ole Petter Clausen Tom Hemming Karlsen Aksel Foss ?ystein Mathisen Erik Schrumpf Ragnhild A. Lothe Guro E. Lind 《Epigenetics》2012,7(11):1249-1257
Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored. 相似文献
75.
C Charlier JS Agerholm W Coppieters P Karlskov-Mortensen W Li G de Jong C Fasquelle L Karim S Cirera N Cambisano N Ahariz E Mullaart M Georges M Fredholm 《PloS one》2012,7(8):e43085
Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that despite the very low incidence of BS (<1/100,000), carrier frequency is as high as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is likely due to the fact that a large proportion of homozygous mutant calves die during pregnancy. We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility, and propose a genotype-driven screening strategy to detect the corresponding deleterious mutations. 相似文献
76.
77.
M Rosenkilde P Auerbach MH Reichkendler T Ploug BM Stallknecht A Sjödin 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,303(6):R571-R579
The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ~30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation. 相似文献
78.
Razvan Anistoroaei Vivi Nielsen Marios Nektarios Markakis Peter Karlskov-Mortensen Claus B. Jørgensen Knud Christensen Merete Fredholm 《Gene》2012
Our previously published second generation genetic map for the American mink (Neovison vison) has been used and redesigned in its best for genome-wide studies with maximum of efficiency. A number of 114 selected markers, including 33 newly developed microsatellite markers from the CHORI-231 mink Bacterial Artificial Chromosome (BAC) library, have been genotyped in a two generation population composed of 1200 individuals. The outcome reassigns the position of some markers on the chromosomes and it produces a more reliable map with a convenient distance between markers. A total of 104 markers mapped to 14 linkage groups corresponding to the mink autosomes. Six markers are unlinked and four markers are allocated to the X chromosome by homology but no linkage was detected. The sex-average linkage map spans 1192 centiMorgans (cM) with an average intermarker distance of 11.4 cM and 1648 cM when the ends of the linkage groups and the autosomal unlinked markers are added. Sex-specific genetic linkage maps were also generated. The male sex-specific map had a total length of 1014.6 cM between the linked markers and an average inter-marker interval of 9.7 cM. The female map has a corresponding length of 1378.6 cM and an average inter-marker interval of 13.3 cM. The study is complemented with additional anchorage for most of the chromosomes of the map by BAC in situ hybridization with clones containing microsatellites strategically selected from the various parts of the genome. This map provides an improved tool for genetic mapping and comparative genomics in mink, also useful for the future assembly of the mink genome sequence when this will be taken forward. 相似文献
79.
A Podolska C Anthon M Bak N Tommerup K Skovgaard PM Heegaard J Gorodkin S Cirera M Fredholm 《BMC genomics》2012,13(1):459
ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus pleuropneumoniae (APP) causes serious lung infections in pigs. Severe damage to the lungs, in many cases deadly, is caused by toxins released by the bacterium and to some degree by host mediated tissue damage. However, understanding of the role of microRNAs in the course of this infectious disease in porcine is still very limited. RESULTS: In this study, the RNA extracted from visually unaffected and necrotic tissue from pigs infected with Actinobacillus pleuropneumoniae was subjected to small RNA deep sequencing. We identified 169 conserved and 11 candidate novel microRNAs in the pig. Of these, 17 were significantly up-regulated in the necrotic sample and 12 were down-regulated. The expression analysis of a number of candidates revealed microRNAs of potential importance in the innate immune response. MiR-155, a known key player in inflammation, was found expressed in both samples. Moreover, miR-664-5p, miR-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection. CONCLUSIONS: This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend annotation of microRNA in pig and provide insight into the role of a number of microRNAs in regulation of bacteria induced immune and inflammatory response in porcine lung. 相似文献
80.
Louarn S Nawrocki A Edelenbos M Jensen DF Jensen ON Collinge DB Jensen B 《Journal of Proteomics》2012,75(3):962-977
Many carrots are discarded during post harvest cold storage due to development of fungal infections, caused by, e.g., Mycocentrospora acerina (liquorice rot). We compared the susceptibility of carrots grown under conventional and organic agricultural practices. In one year, organically cultivated carrots showed 3 × to 7 × more symptoms than conventionally cultivated, when studying naturally occurring disease at 4 and 6 months, respectively. On the other hand, we have developed a bioassay for infection studies of M. acerina on carrots and observed that organic roots were more susceptible after one month of storage than conventional ones, but no differences were apparent after four or six months storage. Levels of polyacetylenes (falcarinol, falcarindiol and falcarindiol-3-acetate) did not change, whereas the isocoumarin phytoalexin (6-methoxymellein) accumulated in infected tissue as well as in healthy tissue opposite the infection. The proteomes of carrot and M. acerina were characterized, the intensity of 33 plant protein spots was significantly changed in infected roots including up regulation of defence and stress response proteins but also a decrease of proteins involved in energy metabolism. This combined metabolic and proteomic study indicates that roots respond to fungal infection through altered metabolism: simultaneous induction of 6-methoxymellein and synthesis of defence related proteins. 相似文献