Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin. The highest expression rates of most PRRs were observed in monocytes and neutrophils. The B cells expressed high levels of TLR1, TLR6, TLR9, TLR10, and RP-105. Only monocytes and γδ T cells were found to respond to Salmonella enterica serovar Typhimurium infection by intensification of PRRs expression. In Th and B cells, PRRs mRNA down-regulation was detected after infection.
- Keywords
- Leukocyte, Pattern-recognition receptors, Pig, Salmonella, Toll-like receptors,
- MeSH
- Down-Regulation MeSH
- Leukocytes metabolism microbiology MeSH
- RNA, Messenger genetics MeSH
- Neutrophils metabolism MeSH
- Swine MeSH
- Immunity, Innate MeSH
- Receptors, Pattern Recognition genetics metabolism MeSH
- Gene Expression Regulation immunology MeSH
- Salmonella typhimurium physiology MeSH
- Salmonella Infections, Animal immunology MeSH
- Serogroup MeSH
- T-Lymphocytes metabolism MeSH
- Toll-Like Receptors genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- RNA, Messenger MeSH
- Receptors, Pattern Recognition MeSH
- Toll-Like Receptors MeSH
Clinical behavior of neuroblastoma (NBL) is remarkably heterogeneous, as it ranges from spontaneous regression to aggressive clinical phenotype and death. There is increasing body of evidence demonstrating that microRNAs could be considered the potential biomarkers for clinical applications in NBL. In this report, we focus on molecular characterization of high-risk as well as low-risk and intermediate-risk NBL cases in the context of the microRNA expression profile that is specific for the given risk category of the disease. We investigated a total of 30 NBL patients, out of whom there were 19 patients with low- to intermediate-risk and 11 with high-risk NBLs as defined by the Clinical Oncology Group. We determined the expression profiles of 754 microRNAs (miRNAs), whereas the miRNA expression levels were normalized to RNU44, mean expression levels were calculated, and data were analyzed by use of the microarray biostatistical approaches. We identified the signature of 38 miRNAs differentially expressed between these groups of NBL patients (P < 0.05): 17 miRNAs were upregulated and 21 miRNAs were downregulated in the tumors of high-risk NBL patients. We confirm some of the previous observations and we report several new microRNAs associated with aggressive NBL, both being relevant subjects for further translational validation and functional studies.
- MeSH
- Infant MeSH
- Humans MeSH
- MicroRNAs genetics metabolism MeSH
- Biomarkers, Tumor genetics MeSH
- Neuroblastoma genetics MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Gene Expression Profiling MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- MicroRNAs MeSH
- Biomarkers, Tumor MeSH
The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
- Keywords
- Annelida, CCF, Discrimination, Earthworm, Immunity, LBP, PAMP, PRR, Phenoloxidase cascade, TLR,
- MeSH
- Annelida immunology MeSH
- Membrane Glycoproteins chemistry genetics metabolism MeSH
- Pathogen-Associated Molecular Pattern Molecules immunology metabolism MeSH
- Immunity, Innate * MeSH
- Acute-Phase Proteins chemistry genetics metabolism MeSH
- Receptors, Pattern Recognition chemistry genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Signal Transduction immunology MeSH
- Tissue Distribution MeSH
- Toll-Like Receptors chemistry genetics metabolism MeSH
- Carrier Proteins chemistry genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- lipopolysaccharide-binding protein MeSH Browser
- Membrane Glycoproteins MeSH
- Pathogen-Associated Molecular Pattern Molecules MeSH
- Acute-Phase Proteins MeSH
- Receptors, Pattern Recognition MeSH
- Toll-Like Receptors MeSH
- Carrier Proteins MeSH
The oviduct provides an optimal environment for the final preparation, transport, and survival of gametes, the fertilization process, and early embryonic development. Most of the studies on reproduction are based on in vitro cell culture models because of the cell's accessibility. It creates opportunities to explore the complexity of directly linked processes between cells. Previous studies showed a significant expression of genes responsible for cell differentiation, maturation, and development during long-term porcine oviduct epithelial cells (POECs) in vitro culture. This study aimed at establishing the transcriptomic profile and comprehensive characteristics of porcine oviduct epithelial cell in vitro cultures, to compare changes in gene expression over time and deliver information about the expression pattern of genes highlighted in specific GO groups. The oviduct cells were collected after 7, 15, and 30 days of in vitro cultivation. The transcriptomic profile of gene expression was compared to the control group (cells collected after the first day). The expression of COL1A2 and LOX was enhanced, while FGFBP1, SERPINB2, and OVGP1 were downregulated at all selected intervals of cell culture in comparison to the 24-h control (p-value < 0.05). Adding new detailed information to the reproductive biology field about the diversified transcriptome profile in POECs may create new future possibilities in infertility treatments, including assisted reproductive technique (ART) programmes, and may be a valuable tool to investigate the potential role of oviduct cells in post-ovulation events.
- Keywords
- RNA processing, cell adhesion, cell migration, intercellular communication, reproductive biology,
- MeSH
- Cell Culture Techniques methods MeSH
- Epithelial Cells * metabolism cytology MeSH
- Cells, Cultured MeSH
- Swine MeSH
- Gene Expression Regulation MeSH
- Gene Expression Profiling MeSH
- Transcriptome * MeSH
- Oviducts metabolism cytology MeSH
- Fallopian Tubes metabolism cytology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.
- MeSH
- Molecular Sequence Annotation MeSH
- Autoimmunity MeSH
- Autoantibodies biosynthesis genetics MeSH
- Antigens, CD genetics immunology MeSH
- Genome-Wide Association Study MeSH
- Diabetes Mellitus, Type 1 genetics immunology pathology MeSH
- Child MeSH
- Adult MeSH
- Immunity, Humoral MeSH
- Interleukin-1 genetics immunology MeSH
- Infant MeSH
- Leukocytes, Mononuclear immunology metabolism pathology MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Primary Cell Culture MeSH
- Immunity, Innate MeSH
- Receptors, CCR3 genetics immunology MeSH
- Gene Expression Regulation immunology MeSH
- Family MeSH
- Signal Transduction MeSH
- Gene Expression Profiling MeSH
- Case-Control Studies MeSH
- Toll-Like Receptors genetics immunology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Autoantibodies MeSH
- CCR3 protein, human MeSH Browser
- Antigens, CD MeSH
- Interleukin-1 MeSH
- Receptors, CCR3 MeSH
- Toll-Like Receptors MeSH
BACKGROUND: The blood flukes of genus Schistosoma are the causative agent of schistosomiasis, a parasitic disease that infects more than 200 million people worldwide. Proteases of schistosomes are involved in critical steps of host-parasite interactions and are promising therapeutic targets. We recently identified and characterized a group of S1 family Schistosoma mansoni serine proteases, including SmSP1 to SmSP5. Expression levels of some SmSPs in S. mansoni are low, and by standard genome sequencing technologies they are marginally detectable at the method threshold levels. Here, we report their spatial gene expression patterns in adult S. mansoni by the high-sensitivity localization assay. METHODOLOGY: Highly sensitive fluorescence in situ RNA hybridization (FISH) was modified and used for the localization of mRNAs encoding individual SmSP proteases (including low-expressed SmSPs) in tissues of adult worms. High sensitivity was obtained due to specifically prepared tissue and probes in combination with the employment of a signal amplification approach. The assay method was validated by detecting the expression patterns of a set of relevant reference genes including SmCB1, SmPOP, SmTSP-2, and Sm29 with localization formerly determined by other techniques. RESULTS: FISH analysis revealed interesting expression patterns of SmSPs distributed in multiple tissues of S. mansoni adults. The expression patterns of individual SmSPs were distinct but in part overlapping and were consistent with existing transcriptome sequencing data. The exception were genes with significantly low expression, which were also localized in tissues where they had not previously been detected by RNA sequencing methods. In general, SmSPs were found in various tissues including reproductive organs, parenchymal cells, esophagus, and the tegumental surface. CONCLUSIONS: The FISH-based assay provided spatial information about the expression of five SmSPs in adult S. mansoni females and males. This highly sensitive method allowed visualization of low-abundantly expressed genes that are below the detection limits of standard in situ hybridization or by RNA sequencing. Thus, this technical approach turned out to be suitable for sensitive localization studies and may also be applicable for other trematodes. The results suggest that SmSPs may play roles in diverse processes of the parasite. Certain SmSPs expressed at the surface may be involved in host-parasite interactions.
- Keywords
- Blood fluke, Fluorescence RNA in situ hybridization, Platyhelminthes, Schistosoma mansoni, Serine proteases, Transcript, mRNA detection,
- MeSH
- Gene Expression * MeSH
- In Situ Hybridization, Fluorescence methods standards MeSH
- Helminth Proteins genetics MeSH
- RNA metabolism MeSH
- Schistosoma mansoni enzymology genetics MeSH
- Serine Proteases genetics MeSH
- Gene Expression Profiling MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Helminth Proteins MeSH
- RNA MeSH
- Serine Proteases MeSH
We report herein that a pentadactyl developmental pattern is evident in early wing morphogenesis of Gallus (chicken) and Struthio (ostrich). Five avascular zones (spatially predestined locations of contiguous metacarpal and phalangeal aggregation) and four interdigital vascular spaces are established by the regression patterns of autopodial vasculature. Transient vestiges of the first and fifth metacarpals are confirmed histologically and histochemically. They lie within the preaxial-most and postaxial-most avascular zones, respectively. These observations reveal conservative patterning of the avian hand and corroborate a II-III-IV metacarpal interpretation, argue for II-III-IV identity of ossified digits in birds, and favour a simple reduction rather than a homeotic shift in terms of the phenotype expressed by Hox genes in the phylogeny of the avian manus. We suggest that gradual, bilateral reduction of phalanges and metacarpals, via apoptosis mediated by BMP, occurred during the evolution of birds (Pyramid Reduction Hypothesis). This is congruent with the establishment of a central wing axis that became co-opted for coordinated movements. On the basis of evidence presented here, the direct avian ancestor is predicted to have been five-fingered with dominant digits (+ metacarpals) as follow: II, III, IV.
- MeSH
- Apoptosis MeSH
- Models, Biological * MeSH
- Genes, Homeobox MeSH
- Wings, Animal embryology MeSH
- Chick Embryo embryology MeSH
- Body Patterning * MeSH
- Struthioniformes embryology genetics MeSH
- Gene Expression Regulation, Developmental MeSH
- Animals MeSH
- Check Tag
- Chick Embryo embryology MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Identification of coordinately regulated genes according to the level of their expression during the time course of a process allows for discovering functional relationships among genes involved in the process. RESULTS: We present a single class classification method for the identification of genes of similar function from a gene expression time series. It is based on a parallel genetic algorithm which is a supervised computer learning method exploiting prior knowledge of gene function to identify unknown genes of similar function from expression data. The algorithm was tested with a set of randomly generated patterns; the results were compared with seven other classification algorithms including support vector machines. The algorithm avoids several problems associated with unsupervised clustering methods, and it shows better performance then the other algorithms. The algorithm was applied to the identification of secondary metabolite gene clusters of the antibiotic-producing eubacterium Streptomyces coelicolor. The algorithm also identified pathways associated with transport of the secondary metabolites out of the cell. We used the method for the prediction of the functional role of particular ORFs based on the expression data. CONCLUSION: Through analysis of a time series of gene expression, the algorithm identifies pathways which are directly or indirectly associated with genes of interest, and which are active during the time course of the experiment.
- MeSH
- Algorithms MeSH
- Chromosomes, Bacterial genetics MeSH
- Computer Simulation MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Gene Expression Profiling * MeSH
- Streptomyces coelicolor classification genetics metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: One of the major challenges in the analysis of gene expression data is to identify local patterns composed of genes showing coherent expression across subsets of experimental conditions. Such patterns may provide an understanding of underlying biological processes related to these conditions. This understanding can further be improved by providing concise characterizations of the genes and situations delimiting the pattern. RESULTS: We propose a method called semantic biclustering with the aim to detect interpretable rectangular patterns in binary data matrices. As usual in biclustering, we seek homogeneous submatrices, however, we also require that the included elements can be jointly described in terms of semantic annotations pertaining to both rows (genes) and columns (samples). To find such interpretable biclusters, we explore two strategies. The first endows an existing biclustering algorithm with the semantic ingredients. The other is based on rule and tree learning known from machine learning. CONCLUSIONS: The two alternatives are tested in experiments with two Drosophila melanogaster gene expression datasets. Both strategies are shown to detect sets of compact biclusters with semantic descriptions that also remain largely valid for unseen (testing) data. This desirable generalization aspect is more emphasized in the strategy stemming from conventional biclustering although this is traded off by the complexity of the descriptions (number of ontology terms employed), which, on the other hand, is lower for the alternative strategy.
- Keywords
- Biclustering, Enrichment analysis, Gene expression, Ontology, Symbolic machine learning,
- MeSH
- Molecular Sequence Annotation MeSH
- Data Mining methods MeSH
- Drosophila melanogaster genetics MeSH
- Semantics * MeSH
- Cluster Analysis MeSH
- Gene Expression Profiling * MeSH
- Machine Learning MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.
- MeSH
- Models, Biological * MeSH
- Chemotaxis MeSH
- Epithelium embryology metabolism MeSH
- Mice, Mutant Strains MeSH
- Mice MeSH
- Edar Receptor genetics metabolism MeSH
- Body Patterning * MeSH
- Signal Transduction * MeSH
- Hair embryology MeSH
- Gene Expression Regulation, Developmental MeSH
- Tooth Germ embryology metabolism MeSH
- Tooth embryology metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Edar protein, mouse MeSH Browser
- Edar Receptor MeSH