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11.
12.
Jean-Louis Spadoni Pierre Rucart Sigrid Le Clerc Dani?lle van Manen Cédric Coulonges Damien Ulveling Vincent Laville Taoufik Labib Lieng Taing Olivier Delaneau Matthieu Montes Hanneke Schuitemaker Josselin Noirel Jean-Fran?ois Zagury 《PloS one》2015,10(9)
Background
Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS.Methods
We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate.Results
Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV. 相似文献13.
Hanneke Jansen Alet H. Wijga Salome Scholtens Gerard H. Koppelman Dirkje S. Postma Bert Brunekreef Johan C. de Jongste Henri?tte A. Smit Ronald P. Stolk 《PloS one》2015,10(4)
Objective
HbA1c is associated with cardiovascular risk in persons without diabetes and cardiovascular risk accumulates over the life course. Therefore, insight in factors determining HbA1c from childhood onwards is important. We investigated (lifestyle) determinants of HbA1c at age 12 years and the effects of growth on change in HbA1c and the tracking of HbA1c between the age of 8 and 12 years.Study Design and Methods
Anthropometric measurements were taken and HbA1c levels were assessed in 955 children without diabetes aged around 12 years participating in the PIAMA birth cohort study. In 363 of these children HbA1c was also measured at age 8 years. Data on parents and children were collected prospectively by questionnaires.Results
We found no significant association between known risk factors for diabetes and HbA1c at age 12 years. Mean(SD) change in HbA1c between ages 8 and 12 years was 0.6(0.7) mmol/mol per year (or 0.1(0.1) %/yr). Anthropometric measures at age 8 and their change between age 8 and 12 years were not associated with the change in HbA1c. 68.9% of the children remained in the same quintile or had an HbA1c one quintile higher or lower at age 8 years compared to age 12 years.Conclusion
The lack of association between known risk factors for diabetes and HbA1c suggest that HbA1c in children without diabetes is relatively unaffected by factors associated with glycaemia. HbA1c at age 8 years is by far the most important predictor of HbA1c at age 12. Therefore, the ranking of HbA1c levels appear to be fairly stable over time. 相似文献14.
Jafar A. Mammadov Wei Chen Ruihua Ren Reetal Pai Wesley Marchione Feyruz Yalçin Hanneke Witsenboer Thomas W. Greene Steven A. Thompson Siva P. Kumpatla 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(3):577-588
The duplicated and the highly repetitive nature of the maize genome has historically impeded the development of true single
nucleotide polymorphism (SNP) markers in this crop. Recent advances in genome complexity reduction methods coupled with sequencing-by-synthesis
technologies permit the implementation of efficient genome-wide SNP discovery in maize. In this study, we have applied Complexity
Reduction of Polymorphic Sequences technology (Keygene N.V., Wageningen, The Netherlands) for the identification of informative
SNPs between two genetically distinct maize inbred lines of North and South American origins. This approach resulted in the
discovery of 1,123 putative SNPs representing low and single copy loci. In silico and experimental (Illumina GoldenGate (GG)
assay) validation of putative SNPs resulted in mapping of 604 markers, out of which 188 SNPs represented 43 haplotype blocks
distributed across all ten chromosomes. We have determined and clearly stated a specific combination of stringent criteria
(>0.3 minor allele frequency, >0.8 GenTrainScore and >0.5 Chi_test100 score) necessary for the identification of highly polymorphic
and genetically stable SNP markers. Due to these criteria, we identified a subset of 120 high-quality SNP markers to leverage
in GG assay-based marker-assisted selection projects. A total of 32 high-quality SNPs represented 21 haplotypes out of 43
identified in this study. The information on the selection criteria of highly polymorphic SNPs in a complex genome such as
maize and the public availability of these SNP assays will be of great value for the maize molecular genetics and breeding
community. 相似文献
15.
Stellingwerff T Boon H Jonkers RA Senden JM Spriet LL Koopman R van Loon LJ 《American journal of physiology. Endocrinology and metabolism》2007,292(6):E1715-E1723
Intramyocellular triacylglycerol (IMTG) has been suggested to represent an important substrate source during exercise. In the present study, IMTG utilization during exercise is assessed through the use of various methodologies. In addition, we identified differences in the use of intramyocellular lipids deposited in the immediate subsarcolemmal (SS) area and those stored in the more central region of the fiber. Contemporary stable isotope technology was applied in combination with muscle tissue sampling before and immediately after 3 h of moderate-intensity cycling exercise (62 +/- 2% Vo(2 max)) in eight well-trained male cyclists. Continuous infusions with [U-13C]palmitate and [6,6-(2)H2]glucose were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate whole body IMTG and glycogen use. Both immunohistochemical analyses of oil red O (ORO)-stained muscle cross sections and biochemical triacylglycerol (TG) extraction were performed to assess muscle lipid content. During exercise, plasma FFA, muscle (and/or lipoprotein)-derived TG, plasma glucose, and muscle glycogen oxidation contributed 24 +/- 2, 22 +/- 3, 11 +/- 1, and 43 +/- 3% to total energy expenditure, respectively. In accordance, a significant net decline in muscle lipid content was observed following exercise as assessed by ORO staining (67 +/- 8%) and biochemical TG extraction (49 +/- 8%), and a positive correlation was observed between methods (r = 0.56; P < 0.05). Lipid depots located in the SS area were utilized to a greater extent than the more centrally located depots. This is the first study to show significant use of IMTG as a substrate source during exercise in healthy males via the concurrent implementation of three major methodologies. In addition, this study shows differences in resting subcellular intramyocellular lipid deposit distribution and in the subsequent net use of these deposits during exercise. 相似文献
16.
Increased neutralization sensitivity of recently emerged CXCR4-using human immunodeficiency virus type 1 strains compared to coexisting CCR5-using variants from the same patient 下载免费PDF全文
Bunnik EM Quakkelaar ED van Nuenen AC Boeser-Nunnink B Schuitemaker H 《Journal of virology》2007,81(2):525-531
CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-using (R5) variants relatively late in the natural course of infection in 50% of HIV-1 subtype B-infected individuals and subsequently coexist with R5 HIV-1 variants. This relatively late appearance of X4 HIV-1 variants is poorly understood. Here we tested the neutralization sensitivity for soluble CD4 (sCD4) and the broadly neutralizing antibodies IgG1b12, 2F5, 4E10, and 2G12 of multiple coexisting clonal R5 and (R5)X4 (combined term for monotropic X4 and dualtropic R5X4 viruses) HIV-1 variants that were obtained at two time points after the first appearance of X4 variants in five participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Recently emerged (R5)X4 viruses were significantly more sensitive to neutralization by the CD4-binding-site-directed agents sCD4 and IgG1b12 than their coexisting R5 viruses. This difference was less pronounced at the later time point. Early (R5)X4 variants from two out of four patients were also highly sensitive to neutralization by autologous serum (50% inhibition at serum dilutions of >200). Late (R5)X4 viruses from these two patients were neutralized at lower serum dilutions, which suggested escape of X4 variants from humoral immunity. Autologous neutralization of coexisting R5 and (R5)X4 variants was not observed in the other patients. In conclusion, the increased neutralization sensitivity of HIV-1 variants during the transition from CCR5 usage to CXCR4 usage may imply an inhibitory role for humoral immunity in HIV-1 phenotype evolution in some patients, thus potentially contributing to the late emergence of X4 variants. 相似文献
17.
Viral replication capacity as a correlate of HLA B57/B5801-associated nonprogressive HIV-1 infection 总被引:6,自引:0,他引:6
Navis M Schellens I van Baarle D Borghans J van Swieten P Miedema F Kootstra N Schuitemaker H 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(5):3133-3143
HLA B57 and the closely related HLA B5801 are over-represented among HIV-1 infected long-term nonprogressors (LTNPs). It has been suggested that this association between HLA B57/5801 and asymptomatic survival is a consequence of strong CTL responses against epitopes in the viral Gag protein. Moreover, CTL escape mutations in Gag would coincide with viral attenuation, resulting in low viral load despite evasion from immune control. In this study we compared HLA B57/5801 HIV-1 infected progressors and LTNPs for sequence variation in four dominant epitopes in Gag and their ability to generate CTL responses against these epitopes and the autologous escape variants. Prevalence and appearance of escape mutations in Gag epitopes and potential compensatory mutations were similar in HLA B57/5801 LTNPs and progressors. Both groups were also indistinguishable in the magnitude of CD8+ IFN-gamma responses directed against the wild-type or autologous escape mutant Gag epitopes in IFN-gamma ELISPOT analysis. Interestingly, HIV-1 variants from HLA B57/5801 LTNPs had much lower replication capacity than the viruses from HLA B57/5801 progressors, which did not correlate with specific mutations in Gag. In conclusion, the different clinical course of HLA B57/5801 LTNPs and progressors was not associated with differences in CTL escape mutations or CTL activity against epitopes in Gag but rather with differences in HIV-1 replication capacity. 相似文献
18.
Gilad AA McMahon MT Walczak P Winnard PT Raman V van Laarhoven HW Skoglund CM Bulte JW van Zijl PC 《Nature biotechnology》2007,25(2):217-219
Existing magnetic resonance reporter genes all rely on the presence of (super)paramagnetic substances and employ water relaxation to gain contrast. We designed a nonmetallic, biodegradable, lysine rich-protein (LRP) reporter, the prototype of a potential family of genetically engineered reporters expressing artificial proteins with frequency-selective contrast. This endogenous contrast, based on transfer of radiofrequency labeling from the reporter's amide protons to water protons, can be switched on and off. 相似文献
19.
A real-time PCR assay is described for detection of the macrolide efflux gene, mef. Following amplification, unambiguous discrimination between the two mef subclasses, mef(A) and mef(E), is easily established using a melting curve analysis. The results of this novel assay were 100% concordant with a conventional PCR-RFLP approach but requires far less hands-on time. Furthermore, the real-time format offers semiquantitative results allowing identification of contaminated cultures and/or DNA preparations. 相似文献
20.
Mechanisms of dsRNA uptake in insects and potential of RNAi for pest control: A review 总被引:7,自引:0,他引:7
Hanneke Huvenne 《Journal of insect physiology》2010,56(3):227-235
RNA interference already proved its usefulness in functional genomic research on insects, but it also has considerable potential for the control of pest insects. For this purpose, the insect should be able to autonomously take up the dsRNA, for example through feeding and digestion in its midgut. In this review we bring together current knowledge on the uptake mechanisms of dsRNA in insects and the potential of RNAi to affect pest insects. At least two pathways for dsRNA uptake in insects are described: the transmembrane channel-mediated uptake mechanism based on Caenorhabditis elegans’ SID-1 protein and an ‘alternative’ endocytosis-mediated uptake mechanism. In the second part of the review dsRNA feeding experiments on insects are brought together for the first time, highlighting the achievement of implementing RNAi in insect control with the first successful experiments in transgenic plants and the diversity of successfully tested insect orders/species and target genes. We conclude with points of discussion and concerns regarding further research on dsRNA uptake mechanisms and the promising application possibilities for RNAi in insect control. 相似文献