The fibroblast growth factors (FGFs) constitute one of the largest growth factor families, and several ligands and receptors in this family are known to play critical roles during tongue development. In order to provide a comprehensive foundation for research into the role of FGFs during the process of tongue formation, we measured the transcript levels by quantitative PCR and mapped the expression patterns by in situ hybridization of all 22 Fgfs during mouse tongue development between embryonic days (E) 11.5 and E14.5. During this period, Fgf5, Fgf6, Fgf7, Fgf9, Fgf10, Fgf13, Fgf15, Fgf16 and Fgf18 could all be detected with various intensities in the mesenchyme, whereas Fgf1 and Fgf2 were expressed in both the epithelium and the mesenchyme. Our results indicate that FGF signaling regulates tongue development at multiple stages.

• Klíčová slova
• Expression, FGF, Papilla, Tongue,
• MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj genetika   MeSH
• epitel růst a vývoj   metabolismus   MeSH
• fibroblastové růstové faktory biosyntéza   genetika   MeSH
• hybridizace in situ MeSH
• jazyk růst a vývoj   metabolismus   MeSH
• mezoderm růst a vývoj   metabolismus   MeSH
• myši MeSH
• organogeneze genetika   MeSH
• signální transdukce MeSH
• vývojová regulace genové exprese genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH

Heterologous expression of the bacterial enzyme haloalkane dehalogenase LinB from Sphingomonas paucimobilis UT26 in methylotrophic yeast Pichia pastoris is reported. The haloalkane dehalogenase gene linB was subcloned into the pPICZalphaA vector and integrated into the genome of P. pastoris. The recombinant LinB secreted from the yeast was purified to homogeneity and biochemically characterized. The deglycosylation experiment and mass spectrometry measurements showed that the recombinant LinB expressed in P. pastoris is glycosylated with a 2.8 kDa size of high mannose core. The specific activity of the glycosylated LinB was 15.6 +/- 3.7 micromol/min/mg of protein with 1,2-dibromoethane and 1.86 +/- 0.36 micromol/min/mg of protein with 1-chlorobutane. Activity and solution structure of the protein produced in P. pastoris is comparable with that of recombinant LinB expressed in Escherichia coli. The melting temperature determined by the circular dichroism (41.7+/-0.3 degrees C for LinB expressed in P. pastoris and 41.8 +/- 0.3 degrees C expressed in E. coli) and thermal stability measured by specific activity to 1-chlorobutane were also similar for two enzymes. Our results show that LinB can be extracellularly expressed in eukaryotic cell and glycosylation had no effect on activity, protein fold and thermal stability of LinB.

• MeSH
• cirkulární dichroismus MeSH
• denaturace proteinů MeSH
• glykosylace MeSH
• hydrolasy chemie   genetika   izolace a purifikace   metabolismus   MeSH
• kinetika MeSH
• klonování DNA MeSH
• konformace proteinů MeSH
• Pichia genetika   MeSH
• regulace genové exprese enzymů MeSH
• regulace genové exprese u bakterií MeSH
• rekombinantní proteiny chemie   izolace a purifikace   metabolismus   MeSH
• Sphingomonas enzymologie   genetika   MeSH
• stabilita enzymů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• haloalkane dehalogenase MeSH Prohlížeč
• hydrolasy MeSH
• rekombinantní proteiny MeSH

BACKGROUND: One possible approach how to economically facilitate gene expression profiling is to use the L1000 platform which measures the expression of ∼1,000 landmark genes and uses a computational method to infer the expression of another ∼10,000 genes. One such method for the gene expression inference is a D-GEX which employs neural networks. RESULTS: We propose two novel D-GEX architectures that significantly improve the quality of the inference by increasing the capacity of a network without any increase in the number of trained parameters. The architectures partition the network into individual towers. Our best proposed architecture - a checkerboard architecture with a skip connection and five towers - together with minor changes in the training protocol improves the average mean absolute error of the inference from 0.134 to 0.128. CONCLUSIONS: Our proposed approach increases the gene expression inference accuracy without increasing the number of weights of the model and thus without increasing the memory footprint of the model that is limiting its usage.

• Klíčová slova
• Checkerboard architecture, Gene expression, Neural network, Tower architecture,
• MeSH
• algoritmy MeSH
• exprese genu MeSH
• genové regulační sítě MeSH
• neuronové sítě * MeSH
• stanovení celkové genové exprese * MeSH
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• Biclustering, Enrichment analysis, Gene expression, Ontology, Symbolic machine learning,
• MeSH
• anotace sekvence MeSH
• data mining metody   MeSH
• Drosophila melanogaster genetika   MeSH
• sémantika * MeSH
• shluková analýza MeSH
• stanovení celkové genové exprese * MeSH
• strojové učení MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it to induce diverse gene expression profiles in subjects living in two regions of the Czech Republic differing in levels and sources of the air pollution. A total of 312 samples from polluted Ostrava region and 154 control samples from Prague were collected in winter 2009, summer 2009 and winter 2010. The highest concentrations of air pollutants were detected in winter 2010 when the subjects were exposed to: PM of aerodynamic diameter <2.5μm (PM2.5) (70 vs. 44.9μg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs. 5.5μg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis of total RNA extracted from leukocytes was performed using Illumina Expression BeadChips microarrays. The expression of selected genes was verified by quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by locations and seasons. Despite lower concentrations of air pollutants a higher number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was found in subjects from Prague. In both locations immune response pathways were affected, in Prague also neurodegenerative diseases-related pathways. Over-representation of the latter pathways was associated with the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in a comparison of winter 2010 and summer 2009. In Prague, an increase in gene expression was observed for GADD45A and PTGS2. In conclusion, high concentrations of pollutants in Ostrava were not associated with higher number of differentially expressed genes, affected KEGG pathways and expression levels of selected genes. This observation suggests that chronic exposure to air pollution may result in reduced gene expression response with possible negative health consequences.

• Klíčová slova
• Air pollution, Chronic exposure, Gene expression profiles, Human health, Particulate matter, Polycyclic aromatic hydrocarbons,
• MeSH
• dospělí MeSH
• látky znečišťující vzduch toxicita   MeSH
• leukocyty metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• regulace genové exprese * MeSH
• roční období * MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch MeSH

Lactococcus garvieae has emerged as an important zoonotic pathogen. However, information regarding mechanisms and factors related to its pathogenicity is lacking. In the present study, we investigated the distribution and functionality of genes related to virulence factors in L. garvieae strains isolated from different niches (diseased fish, humans, meat and dairy products, vegetables), using both post-genomic and genotypic analysis. Putative genes encoding hemolysin, fibronectin-binding protein, and penicillin acylase were detected in all analyzed genomes/strains. Their expression was significantly induced by bile salt stress. Putative genes encoding bile salt hydrolase were found in a few strains from dairy and human sources, as well as the mobilizable tet genes. Finally, all genomes possessed a folate gene cluster, in which mutations in the dihydropteroate synthase gene (folP) could be related to sulfonamide resistance. To the best of our knowledge, this is the first study aimed to explore the pathogenic potential of L. garvieae through the analysis of numerous L. garvieae genomes/strains, coming from different sources. This approach allowed the detection of virulence-related genes not yet investigated in the species and the study of their expression after exposure to different environmental stresses. The results obtained suggest a virulence potential in some L. garvieae strains that can be exploited for survival in the human gastrointestinal tract.

• Klíčová slova
• Emerging zoonotic pathogen, Gene expression studies, Lactococcus garvieae, Virulence genes,
• MeSH
• DNA bakterií genetika   MeSH
• faktory virulence genetika   MeSH
• genomika * MeSH
• Lactococcus genetika   růst a vývoj   patogenita   MeSH
• lidé MeSH
• regulace genové exprese u bakterií * MeSH
• stanovení celkové genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA bakterií MeSH
• faktory virulence MeSH

The mediator (MED) represents a large, conserved, multi-subunit protein complex that regulates gene expression through interactions with RNA polymerase II and enhancer-bound transcription factors. Expanding research accomplishments suggest the predominant role of plant MED subunits in the regulation of various physiological and developmental processes, including the biotic stress response against bacterial and fungal pathogens. However, the involvement of MED subunits in virus/viroid pathogenesis remains elusive. In this study, we investigated for the first time the gene expression modulation of selected MED subunits in response to five viroid species (Apple fruit crinkle viroid (AFCVd), Citrus bark cracking viroid (CBCVd), Hop latent viroid (HLVd), Hop stunt viroid (HSVd), and Potato spindle tuber viroid (PSTVd)) in two model plant species (Nicotiana tabacum and N. benthamiana) and a commercially important hop (Humulus lupulus) cultivar. Our results showed a differential expression pattern of MED subunits in response to a viroid infection. The individual plant MED subunits displayed a differential and tailored expression pattern in response to different viroid species, suggesting that the MED expression is viroid- and plant species-dependent. The explicit evidence obtained from our results warrants further investigation into the association of the MED subunit with symptom development. Together, we provide a comprehensive portrait of MED subunit expression in response to viroid infection and a plausible involvement of MED subunits in fine-tuning transcriptional reprogramming in response to viroid infection, suggesting them as a potential candidate for rewiring the defense response network in plants against pathogens.

• Klíčová slova
• Nicotiana benthamiana, Nicotiana tabacum, differential expression, hop, mediator complex, pathogen, quantitative reverse transcription PCR, viroid,
• MeSH
• druhová specificita MeSH
• Humulus genetika   virologie   MeSH
• listy rostlin genetika   mikrobiologie   MeSH
• mediátorový komplex genetika   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné proteiny genetika   MeSH
• rostlinné viry MeSH
• stanovení celkové genové exprese MeSH
• tabák genetika   virologie   MeSH
• viroidy genetika   patogenita   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mediátorový komplex MeSH
• rostlinné proteiny MeSH

In this paper, correlation analysis of protein and mRNA levels in the soil dwelling bacteria Streptomyces coelicolor (S. coelicolor M145) is presented during development of the population as it grew in liquid medium using three biological and two technical replicates, measured during exponential growth, and its entry into the stationary phase. The proteome synthesis time series are compared with the gene expression time series measured previously under identical experimental conditions. Results reveal that about one third of protein/mRNA synthesis profiles are well correlated while another third are correlated negatively. Functional analysis of the highly correlated groups is presented. Based on numerical simulation, the negative correlation between protein and mRNA is shown to be caused by the difference between the rate of translation and protein degradation.

• Klíčová slova
• Streptomyces, computational modeling, mRNA/protein expression, mass spectrometry, proteins functional analysis,
• MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteom analýza   metabolismus   MeSH
• půda chemie   MeSH
• regulace genové exprese u bakterií MeSH
• stanovení celkové genové exprese MeSH
• Streptomyces coelicolor genetika   růst a vývoj   metabolismus   MeSH
• transkriptom * MeSH
• vývojová regulace genové exprese * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• messenger RNA MeSH
• proteom MeSH
• půda MeSH

Cardiovascular defects are one of the most common congenital defects associated with maternal diabetes. Based on whole embryo gene expression microarray analysis, 11 genes were chosen for temporal expression analysis of diabetes-exposed hearts. The majority of the selected genes were deregulated in diabetes-exposed hearts compared to our controls at E13.5, E14.5, and E18.5. We showed increased hypoxia and HIF-1α protein levels in diabetes-exposed hearts at E10.5, which is a critical time point for the induction of developmental defects associated with diabetic embryopathy. Additionally, we found increased cardiac Vegfa levels that might trigger developmental abnormalities associated with diabetic embryopathy. Our results show that maternal diabetes affects the temporal expression pattern of gene encoding molecules involved in heart development and tissue remodelling and that these molecules might affect heart maturation processes and thus, the final outcome of diabetic pregnancies.

• Klíčová slova
• Cardiovascular defects, Diabetic embryopathy, Gene expression, Vascular endothelial growth factor A (VEGF-A),
• MeSH
• embryo savčí MeSH
• experimentální diabetes mellitus genetika   metabolismus   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• hypoxie genetika   metabolismus   MeSH
• inbrední kmeny myší MeSH
• messenger RNA metabolismus   MeSH
• myokard metabolismus   MeSH
• srdce embryologie   MeSH
• stanovení celkové genové exprese MeSH
• těhotenství při diabetu genetika   metabolismus   MeSH
• těhotenství MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• Hif1a protein, mouse MeSH Prohlížeč
• messenger RNA MeSH
• vascular endothelial growth factor A, mouse MeSH Prohlížeč
• vaskulární endoteliální růstový faktor A MeSH

OBJECTIVE: This study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor-positive (ER+) breast carcinomas via interaction with endocrine therapy. CONTEXT: The prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti-oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy. DESIGN: The expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance. PATIENTS: A total of 193 primary patients with breast carcinoma were included. MEASUREMENTS: The transcript levels were determined by quantitative real-time polymerase chain reaction. RESULTS: The expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER- tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease-free survival in patients treated with endocrine therapy. CONCLUSIONS: The expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.

• Klíčová slova
• breast carcinoma, expression, oestrogen receptor, oxysterols, prognosis,
• MeSH
• biosyntetické dráhy genetika   MeSH
• cholesterol farmakologie   MeSH
• endokrinní systém MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu diagnóza   genetika   metabolismus   MeSH
• oxysteroly metabolismus   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• receptory pro estrogeny analýza   MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol MeSH
• oxysteroly MeSH
• receptory pro estrogeny MeSH