Non-coding RNAs (ncRNAs) are regulatory molecules encoded in the intergenic or intragenic regions of the genome. In prokaryotes, biocomputational identification of homologs of known ncRNAs in other species often fails due to weakly evolutionarily conserved sequences, structures, synteny and genome localization, except in the case of evolutionarily closely related species. To eliminate results from weak conservation, we focused on RNA structure, which is the most conserved ncRNA property. Analysis of the structure of one of the few well-studied bacterial ncRNAs, 6S RNA, demonstrated that unlike optimal and consensus structures, suboptimal structures are capable of capturing RNA homology even in divergent bacterial species. A computational procedure for the identification of homologous ncRNAs using suboptimal structures was created. The suggested procedure was applied to strongly divergent bacterial species and was capable of identifying homologous ncRNAs.

• MeSH
• bakteriální RNA chemie   MeSH
• konformace nukleové kyseliny MeSH
• molekulární sekvence - údaje MeSH
• Mycobacterium genetika   MeSH
• nekódující RNA chemie   MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie nukleových kyselin MeSH
• Streptomyces genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• centrální nervový systém anatomie a histologie   MeSH
• denzitometrie MeSH
• kočky MeSH
• sekvenční homologie MeSH
• Check Tag
• kočky MeSH

V období od roku 1992 až do 1. 9. 1998 byl sledován počet žádostí českých transplantačních center o vyhledávání nepříbuzného dárce kostní dřeně, indikace k nepříbuzenské transplanta- ci, doba potřebná k vyhledávání nepříbuzného dárce a úspěšnost vyhledávání mezi českými dobrovolníky. Počet žádostí o vyhledání nepříbuzného dárce dřeně každoročně stoupal, přičemž indikace k transplantaci zcela odpovídaly mezinárodním zkušenostem. Doba potřebná k vyhle- dání dárce se každoročně zkracovala a v posledním roce sledování činila méně než 1 měsíc u 70 % žádostí. Pro téměř 20 % nemocných byl nepříbuzný dárce nalezen mezi českými dobrovolníky. U 13 nemocných nebyla transplantace uskutečněna přes nalezení dárce pro úmrtí pacienta či relaps základní choroby. Na základě dosavadních zkušeností lze do budoucna pokládat za nejdůležitější včasné zahájení vyhledávání nepříbuzného dárce, a to v okamžiku nenalezení dárce v úzké rodině, a další zlepšení spolupráce mezi indikujícími transplantačními centry a registry.

During the period from 1992 till Sept. 1, 1998 the number of applications of Czech transplan- tation centres for „non-related“ bone marrow donors was recorded, as well as indications for transplantations from non-related subjects, the time needed to find a donor and the success rate among Czech volunteers. The number of applications for a non-related bone marrow donor increased every year whereby indications for transplantation were consistent with internatio- nal experience. The time needed to find a donor declined every year and during the last year of the investigation it was less than one month in 70% of the applications. For almost 20% of the patients a non-related donor was found among Czech volunteers. In 13 patients the transplan- tation was not implemented although a donor was found because of the patient’s death or relapse of the basic disease. Based on hitherto assembled experience it may be in future considered most important to start in time with the search for a non-related donor when a suitable donor is not found in the family, and ensure better collaboration between indicating transplantation centres and registers.

• MeSH
• dárci tkání MeSH
• homologní transplantace MeSH
• lidé MeSH
• preferované dárcovské organizace MeSH
• testování histokompatibility MeSH
• transplantace kostní dřeně MeSH
• Check Tag
• lidé MeSH

In this paper, we present a novel algorithm for measuring protein similarity based on their 3-D structure (protein tertiary structure). The algorithm used a suffix tree for discovering common parts of main chains of all proteins appearing in the current research collaboratory for structural bioinformatics protein data bank (PDB). By identifying these common parts, we build a vector model and use some classical information retrieval (IR) algorithms based on the vector model to measure the similarity between proteins--all to all protein similarity. For the calculation of protein similarity, we use term frequency × inverse document frequency ( tf × idf ) term weighing schema and cosine similarity measure. The goal of this paper is to introduce new protein similarity metric based on suffix trees and IR methods. Whole current PDB database was used to demonstrate very good time complexity of the algorithm as well as high precision. We have chosen the structural classification of proteins (SCOP) database for verification of the precision of our algorithm because it is maintained primarily by humans. The next success of this paper would be the ability to determine SCOP categories of proteins not included in the latest version of the SCOP database (v. 1.75) with nearly 100% precision.

• MeSH
• algoritmy MeSH
• data mining metody   MeSH
• databáze proteinů MeSH
• lidé MeSH
• proteiny chemie   MeSH
• reprodukovatelnost výsledků MeSH
• strukturní homologie proteinů MeSH
• terciární struktura proteinů MeSH
• umělá inteligence MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.

• MeSH
• alely * MeSH
• algoritmy * MeSH
• datové soubory jako téma MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA antigeny klasifikace   genetika   imunologie   MeSH
• homologní transplantace MeSH
• lidé MeSH
• nepříbuzný dárce MeSH
• příjemce transplantátu MeSH
• registrace * MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• transplantace kmenových buněk z pupečníkové krve * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• srovnávací studie MeSH

Searching for similar sequences in a database via BLAST or a similar tool is one of the most common bioinformatics tasks applied in general, and to non-coding RNAs in particular. However, the results of the search might be difficult to interpret due to the presence of partial matches to the database subject sequences. Here, we present rboAnalyzer - a tool that helps with interpreting sequence search result by (1) extending partial matches into plausible full-length subject sequences, (2) predicting homology of RNAs represented by full-length subject sequences to the query RNA, (3) pooling information across homologous RNAs found in the search results and public databases such as Rfam to predict more reliable secondary structures for all matches, and (4) contextualizing the matches by providing the prediction results and other relevant information in a rich graphical output. Using predicted full-length matches improves secondary structure prediction and makes rboAnalyzer robust with regards to identification of homology. The output of the tool should help the user to reliably characterize non-coding RNAs in BLAST output. The usefulness of the rboAnalyzer and its ability to correctly extend partial matches to full-length is demonstrated on known homologous RNAs. To allow the user to use custom databases and search options, rboAnalyzer accepts any search results as a text file in the BLAST format. The main output is an interactive HTML page displaying the computed characteristics and other context of the matches. The output can also be exported in an appropriate sequence and/or secondary structure formats.

• Publikační typ
• časopisecké články MeSH

Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly.

• MeSH
• biologické modely MeSH
• buněčné jádro metabolismus   MeSH
• genový knockout MeSH
• histonacetyltransferasy metabolismus   MeSH
• imunoprecipitace MeSH
• interleukin-1alfa chemie   metabolismus   MeSH
• lidé MeSH
• podjednotky proteinů metabolismus   MeSH
• protein-serin-threoninkinasy chemie   metabolismus   MeSH
• proteinkinasy aktivované AMP chemie   metabolismus   MeSH
• proteinové prekurzory chemie   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny metabolismus   MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• signální transdukce MeSH
• strukturní homologie proteinů MeSH
• subcelulární frakce metabolismus   MeSH
• terciární struktura proteinů MeSH
• trans-aktivátory metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• výpočetní biologie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acetylcholinesterase (AChE) is a widely spread enzyme playing a very important role in nerve signal transmission. As AChE controls key processes, its inhibition leads to the very fast death of an organism, including humans. However, when this feature is to be used for killing of unwanted organisms (i.e. mosquitoes), one is faced with the question - how much do AChEs differ between species and what are the differences? Here, a theoretical point of view was utilized to identify the structural basis for such differences. The various primary and tertiary alignments show that AChEs are very evolutionary conserved enzymes and this fact could lead to difficulties, for example, in the search for inhibitors specific for a particular species.

• MeSH
• acetylcholinesterasa chemie   MeSH
• Drosophila melanogaster metabolismus   MeSH
• financování organizované MeSH
• konformace proteinů MeSH
• konzervovaná sekvence MeSH
• lidé MeSH
• molekulární evoluce MeSH
• molekulární konformace MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• sbalování proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• signální transdukce MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH

Mice deficient in Klotho gene expression exhibit a syndrome resembling premature human aging. To determine whether variation in the human KLOTHO locus contributes to survival, we applied two newly characterized polymorphic microsatellite markers flanking the gene in a population-based association study. In a cohort chosen for its homogeneity, Bohemian Czechs, we demonstrated significant differences in selected marker allele frequencies between newborn and elderly individuals (P < 0.05). These results precipitated a search for functional variants of klotho. We identified an allele, termed KL-VS, containing six sequence variants in complete linkage disequilibrium, two of which result in amino acid substitutions F352V and C370S. Homozygous elderly individuals were underrepresented in three distinct populations: Bohemian Czechs, Baltimore Caucasians, and Baltimore African-Americans [combined odds ratio (OR) = 2.59, P < 0.0023]. In a transient transfection assay, secreted levels of klotho harboring V352 are reduced 6-fold, whereas extracellular levels of the S370 form are increased 2.9-fold. The V352/S370 double mutant exhibits an intermediate phenotype (1.6-fold increase), providing a rare example of intragenic complementation in cis by human single nucleotide polymorphisms. The remarkable conservation of F352 among homologous proteins suggests that it is functionally important. The corresponding substitution, F289V, in the closest human klotho paralog with a known substrate, cBGL1, completely eliminates its ability to cleave p-nitrophenyl-beta-D-glucoside. These results suggest that the KL-VS allele influences the trafficking and catalytic activity of klotho, and that variation in klotho function contributes to heterogeneity in the onset and severity of human age-related phenotypes.

• MeSH
• alely MeSH
• genetická variace MeSH
• glukuronidasa MeSH
• kohortové studie MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• novorozenec MeSH
• populační genetika MeSH
• předčasné stárnutí genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• novorozenec MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geografické názvy
• Baltimore MeSH
• Česká republika MeSH

BACKGROUND: Type I restriction-modification (R-M) systems are the most complex restriction enzymes discovered to date. Recent years have witnessed a renaissance of interest in R-M enzymes Type I. The massive ongoing sequencing programmes leading to discovery of, so far, more than 1 000 putative enzymes in a broad range of microorganisms including pathogenic bacteria, revealed that these enzymes are widely represented in nature. The aim of this study was characterisation of a putative R-M system EcoA0ORF42P identified in the commensal Escherichia coli A0 34/86 (O83: K24: H31) strain, which is efficiently used at Czech paediatric clinics for prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants. RESULTS: We have characterised a restriction-modification system EcoA0ORF42P of the commensal Escherichia coli strain A0 34/86 (O83: K24: H31). This system, designated as EcoAO83I, is a new functional member of the Type IB family, whose specificity differs from those of known Type IB enzymes, as was demonstrated by an immunological cross-reactivity and a complementation assay. Using the plasmid transformation method and the RM search computer program, we identified the DNA recognition sequence of the EcoAO83I as GGA(8N)ATGC. In consistence with the amino acids alignment data, the 3' TRD component of the recognition sequence is identical to the sequence recognized by the EcoEI enzyme. The A-T (modified adenine) distance is identical to that in the EcoAI and EcoEI recognition sites, which also indicates that this system is a Type IB member. Interestingly, the recognition sequence we determined here is identical to the previously reported prototype sequence for Eco377I and its isoschizomers. CONCLUSION: Putative restriction-modification system EcoA0ORF42P in the commensal Escherichia coli strain A0 34/86 (O83: K24: H31) was found to be a member of the Type IB family and was designated as EcoAO83I. Combination of the classical biochemical and bacterial genetics approaches with comparative genomics might contribute effectively to further classification of many other putative Type-I enzymes, especially in clinical samples.

• MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• DNA restrikčně-modifikační enzymy genetika   metabolismus   MeSH
• Escherichia coli enzymologie   genetika   MeSH
• financování organizované MeSH
• genomika MeSH
• proteiny z Escherichia coli genetika   metabolismus   MeSH
• protilátky bakteriální metabolismus   MeSH
• restrikční endonukleasy typu I genetika   metabolismus   MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie nukleových kyselin MeSH
• sekvenční seřazení MeSH
• testy genetické komplementace MeSH