154 research outputs found

    The absorption of certain radicals by leaves in varying stages of decay, and the effect of leaves on the absorption of these radicals by a soil

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    The subject of soil absorption is an old one, dating back to before 1850. The nature of soil absorption has been, and still is, a puzzle, in spite of the vast amount of work that has been done in the last few years. Two theories have been held as the cause of the absorption. The first is that the absorption is chemical, the compounds being changed into insoluble ones by double decomposition. The second is that the salts or radicals are physically held, that is, adsorbed by the soil particles. These theories have been held separately and combined

    Evidence for genes controlling resistance to Heligmosomoides bakeri on mouse chromosome 1

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    Resistance to infections with Heligmosomoides bakeri is associated with a significant quantitative trait locus (QTL–Hbnr1) on mouse chromosome 1 (MMU1). We exploited recombinant mice, with a segment of MMU1 from susceptible C57Bl/10 mice introgressed onto MMU1 in intermediate responder NOD mice (strains 1094 and 6109). BALB/c (intermediate responder) and C57Bl/6 mice (poor responder) were included as control strains and strain 1098 (B10 alleles on MMU3) as NOD controls. BALB/c mice resisted infection rapidly and C57Bl/6 accumulated heavy worm burdens. Fecal egg counts dropped by weeks 10–11 in strain 1098, but strains 1094 and 6109 continued to produce eggs, harbouring more worms when autopsied (day 77). PubMed search identified 3 genes (Ctla4, Cd28, Icos) as associated with ‘Heligmosomoides’ in the B10 insert. Single nucleotide polymorphism (SNP) differences in Ctla4 could be responsible for regulatory changes in gene function, and a SNP within a splice site in Cd28 could have an impact on function, but no polymorphisms with predicted effects on function were found in Icos. Therefore, one or more genes encoded in the B10 insert into NOD mice contribute to the response phenotype, narrowing down the search for genes underlying the H. bakeri resistance QTL, and suggest Cd28 and Ctla4 as candidate genes

    The quality of methods reporting in parasitology experiments

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    There is a growing concern both inside and outside the scientific community over the lack of reproducibility of experiments. The depth and detail of reported methods are critical to the reproducibility of findings, but also for making it possible to compare and integrate data from different studies. In this study, we evaluated in detail the methods reporting in a comprehensive set of trypanosomiasis experiments that should enable valid reproduction, integration and comparison of research findings. We evaluated a subset of other parasitic (Leishmania, Toxoplasma, Plasmodium, Trichuris and Schistosoma) and non-parasitic (Mycobacterium) experimental infections in order to compare the quality of method reporting more generally. A systematic review using PubMed (2000-2012) of all publications describing gene expression in cells and animals infected with Trypanosoma spp was undertaken based on PRISMA guidelines; 23 papers were identified and included. We defined a checklist of essential parameters that should be reported and have scored the number of those parameters that are reported for each publication. Bibliometric parameters (impact factor, citations and h-index) were used to look for association between Journal and Author status and the quality of method reporting. Trichuriasis experiments achieved the highest scores and included the only paper to score 100% in all criteria. The mean of scores achieved by Trypanosoma articles through the checklist was 65.5% (range 32-90%). Bibliometric parameters were not correlated with the quality of method reporting (Spearman's rank correlation coefficient <-0.5; p>0.05). Our results indicate that the quality of methods reporting in experimental parasitology is a cause for concern and it has not improved over time, despite there being evidence that most of the assessed parameters do influence the results. We propose that our set of parameters be used as guidelines to improve the quality of the reporting of experimental infection models as a pre-requisite for integrating and comparing sets of data

    TIGERi: modeling and visualizing the responses to perturbation of a transcription factor network

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    Abstract Background Transcription factor (TF) networks play a key role in controlling the transfer of genetic information from gene to mRNA. Much progress has been made on understanding and reverse-engineering TF network topologies using a range of experimental and theoretical methodologies. Less work has focused on using these models to examine how TF networks respond to changes in the cellular environment. Methods In this paper, we have developed a simple, pragmatic methodology, TIGERi (Transcription-factor-activity Illustrator for Global Explanation of Regulatory interaction), to model the response of an inferred TF network to changes in cellular environment. The methodology was tested using publicly available data comparing gene expression profiles of a mouse p38α (Mapk14) knock-out line to the original wild-type. Results Using the model, we have examined changes in the TF network resulting from the presence or absence of p38α. A part of this network was confirmed by experimental work in the original paper. Additional relationships were identified by our analysis, for example between p38α and HNF3, and between p38α and SOX9, and these are strongly supported by published evidence. FXR and MYC were also discovered in our analysis as two novel links of p38α. To provide a computational methodology to the biomedical communities that has more user-friendly interface, we also developed a standalone GUI (graphical user interface) software for TIGERi and it is freely available at https://github.com/namshik/tigeri/ . Conclusions We therefore believe that our computational approach can identify new members of networks and new interactions between members that are supported by published data but have not been integrated into the existing network models. Moreover, ones who want to analyze their own data with TIGERi could use the software without any command line experience. This work could therefore accelerate researches in transcriptional gene regulation in higher eukaryotes

    Strong position-dependent effects of sequence mismatches on signal ratios measured using long oligonucleotide microarrays

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    <p>Abstract</p> <p>Background</p> <p>Microarrays are an important and widely used tool. Applications include capturing genomic DNA for high-throughput sequencing in addition to the traditional monitoring of gene expression and identifying DNA copy number variations. Sequence mismatches between probe and target strands are known to affect the stability of the probe-target duplex, and hence the strength of the observed signals from microarrays.</p> <p>Results</p> <p>We describe a large-scale investigation of microarray hybridisations to murine probes with known sequence mismatches, demonstrating that the effect of mismatches is strongly position-dependent and for small numbers of sequence mismatches is correlated with the maximum length of perfectly matched probe-target duplex. Length of perfect match explained 43% of the variance in log<sub>2 </sub>signal ratios between probes with one and two mismatches. The correlation with maximum length of perfect match does not conform to expectations based on considering the effect of mismatches purely in terms of reducing the binding energy. However, it can be explained qualitatively by considering the entropic contribution to duplex stability from configurations of differing perfect match length.</p> <p>Conclusion</p> <p>The results of this study have implications in terms of array design and analysis. They highlight the significant effect that short sequence mismatches can have upon microarray hybridisation intensities even for long oligonucleotide probes.</p> <p>All microarray data presented in this study are available from the GEO database <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>, under accession number [GEO: GSE9669]</p

    SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study.

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    Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested ( APOL1 [ G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA , IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected pTrypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies

    Genotype and expression analysis of two inbred mouse strains and two derived congenic strains suggest that most gene expression is trans regulated and sensitive to genetic background

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    <p>Abstract</p> <p>Background</p> <p>Differences in gene expression may be caused by nearby DNA polymorphisms (<it>cis </it>regulation) or by interactions of gene control regions with polymorphic transcription factors (<it>trans </it>regulation). <it>Trans </it>acting loci are much harder to detect than <it>cis </it>acting loci and their effects are much more sensitive to genetic background.</p> <p>Results</p> <p>To quantify <it>cis </it>and <it>trans </it>regulation we correlated haplotype data with gene expression in two inbred mouse strains and two derived congenic lines. Upstream haplotype differences between the parental strains suggested that 30-43% of differentially expressed genes were differentially expressed because of <it>cis </it>haplotype differences. These <it>cis </it>regulated genes displayed consistent and relatively tissue-independent differential expression. We independently estimated from the congenic mice that 71-85% of genes were <it>trans </it>regulated. <it>Cis </it>regulated genes were associated with low p values (p < 0.005) for differential expression, whereas <it>trans </it>regulated genes were associated with values 0.005 < p < 0.05. The genes differentially expressed between congenics and controls were not a subset of those that were differentially expressed between the founder lines, showing that these were dependent on genetic background. For example, the cholesterol synthesis pathway was strongly differentially expressed in the congenic mice by indirect <it>trans </it>regulation but this was not observable in the parental mice.</p> <p>Conclusions</p> <p>The evidence that most gene regulation is <it>trans </it>and strongly influenced by genetic background, suggests that pathways that are modified by an allelic variant, may only exhibit differential expression in the specific genetic backgrounds in which they were identified. This has significant implications for the interpretation of any QTL mapping study.</p

    SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study

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    Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self- cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested (APOL1 [G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA, IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p &lt; 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p&lt;0.05) with a differential risk of developing a Trypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies

    Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data using universal protein motifs

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    African trypanosomes are vector-borne hemoparasites of humans and animals. In the mammal, parasites evade the immune response through antigenic variation. Periodic switching of the Variant Surface Glycoprotein (VSG) coat covering their cell surface allows sequential expansion of serologically distinct parasite clones. Trypanosome genomes contain many hundreds of VSG genes, subject to rapid changes in nucleotide sequence, copy number and chromosomal position. Thus, analysing, or even quantifying, VSG diversity over space and time presents an enormous challenge to conventional techniques. Indeed, previous population genomic studies have overlooked this vital aspect of pathogen biology for lack of analytical tools. Here we present a method for analysing population-scale VSG diversity in Trypanosoma congolense from deep sequencing data. Previously, we suggested that T. congolense VSG segregate into defined 'phylotypes' that do not recombine. In our dataset comprising 41 T. congolense genome sequences from across Africa, these phylotypes are universal and exhaustive. Screening sequence contigs with diagnostic protein motifs accurately quantifies relative phylotype frequencies, providing a metric of VSG diversity, called the 'Variant Antigen Profile'. We applied our metric to VSG expression in the tsetse fly, showing that certain, rare VSG phylotypes may be preferentially expressed in infective, metacyclic-stage parasites. Hence, variant antigen profiling accurately and rapidly determines VSG gene and transcript repertoire from sequence data, without need for manual curation or highly contiguous sequences. It offers a tractable approach to measuring VSG diversity across strains and during infections, which is imperative to understanding the host-parasite interaction at population and individual scales. [Abstract copyright: Published by Cold Spring Harbor Laboratory Press.
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