HLA-A*29:172 allele differs from HLA-A*29:01:01:01 by one missense single C/G nucleotide exchange in codon 77.
- MeSH
- alely MeSH
- exony genetika MeSH
- exprese genu MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční seřazení MeSH
- testování histokompatibility MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Since the publication of the first chicken genome sequence, we have encountered genes playing key roles in mammalian immunology, but being seemingly absent in birds. One of those was, until recently, Foxp3, the master transcription factor of regulatory T cells in mammals. Therefore, avian regulatory T cell research is still poorly standardized. In this study we identify a chicken ortholog of Foxp3 We prove sequence homology with known mammalian and sauropsid sequences, but also reveal differences in major domains. Expression profiling shows an association of Foxp3 and CD25 expression levels in CD4+CD25+ peripheral T cells and identifies a CD4-CD25+Foxp3high subset of thymic lymphocytes that likely represents yet undescribed avian regulatory T precursor cells. We conclude that Foxp3 is existent in chickens and that it shares certain functional characteristics with its mammalian ortholog. Nevertheless, pathways for regulatory T cell development and Foxp3 function are likely to differ between mammals and birds. The identification and characterization of chicken Foxp3 will help to define avian regulatory T cells and to analyze their functional properties and thereby advance the field of avian immunology.
- MeSH
- aktivace lymfocytů imunologie MeSH
- buněčná diferenciace imunologie MeSH
- forkhead transkripční faktory genetika MeSH
- genom genetika MeSH
- kur domácí genetika imunologie MeSH
- receptor interleukinu-2 - alfa-podjednotka metabolismus MeSH
- regulační T-lymfocyty imunologie MeSH
- sekvence aminokyselin genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie MeSH
- sekvenční seřazení MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases RIG-I gene loss has been detected in mammalian and avian species, most notably in the chicken, MDA5 pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of MDA5 in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the MDA5 pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the MDA5 loss does not appear to have resulted in any compensatory evolution in the RIG-I gene, which may partially share its ligand-binding specificity. Together, our results indicate that the MDA5 pseudogenization may have important functional effects on immune responsiveness in these two avian clades.
- MeSH
- DEAD box protein 58 chemie genetika imunologie MeSH
- delece genu * MeSH
- fylogeneze MeSH
- lidé MeSH
- molekulární modely MeSH
- přirozená imunita MeSH
- pseudogeny MeSH
- ptačí proteiny chemie genetika imunologie MeSH
- ptáci klasifikace genetika imunologie MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The enormous sequence heterogeneity of telomerase RNA (TR) subunits has thus far complicated their characterization in a wider phylogenetic range. Our recent finding that land plant TRs are, similarly to known ciliate TRs, transcribed by RNA polymerase III and under the control of the type-3 promoter, allowed us to design a novel strategy to characterize TRs in early diverging Viridiplantae taxa, as well as in ciliates and other Diaphoretickes lineages. Starting with the characterization of the upstream sequence element of the type 3 promoter that is conserved in a number of small nuclear RNAs, and the expected minimum TR template region as search features, we identified candidate TRs in selected Diaphoretickes genomes. Homologous TRs were then used to build covariance models to identify TRs in more distant species. Transcripts of the identified TRs were confirmed by transcriptomic data, RT-PCR and Northern hybridization. A templating role for one of our candidates was validated in Physcomitrium patens. Analysis of secondary structure demonstrated a deep conservation of motifs (pseudoknot and template boundary element) observed in all published TRs. These results elucidate the evolution of the earliest eukaryotic TRs, linking the common origin of TRs across Diaphoretickes, and underlying evolutionary transitions in telomere repeats.
- MeSH
- genetická transkripce MeSH
- konformace nukleové kyseliny MeSH
- molekulární evoluce * MeSH
- mutace MeSH
- RNA rostlin biosyntéza chemie genetika MeSH
- RNA-polymerasa II metabolismus MeSH
- RNA-polymerasa III metabolismus MeSH
- RNA biosyntéza chemie genetika MeSH
- sekvenční seřazení MeSH
- telomerasa biosyntéza chemie genetika MeSH
- telomery chemie MeSH
- transkriptom MeSH
- Viridiplantae genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Helicobacter pylori (Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA. These metabolites are synthesized by Hp xanthine-guanine-hypoxanthine phosphoribosyltransferase (XGHPRT). Here, nucleoside phosphonates have been evaluated, which inhibit the activity of this enzyme with Ki values as low as 200 nM. The prodrugs of these compounds arrest the growth of Hp at a concentration of 50 μM in cell-based assays. The kinetic properties of HpXGHPRT have been determined together with its X-ray crystal structure in the absence and presence of 9-[(N-3-phosphonopropyl)-aminomethyl-9-deazahypoxanthine, providing a basis for new antibiotic development.
- MeSH
- antibakteriální látky chemie metabolismus farmakologie terapeutické užití MeSH
- bakteriální proteiny chemie metabolismus MeSH
- gastrointestinální nemoci farmakoterapie mikrobiologie patologie MeSH
- Helicobacter pylori účinky léků enzymologie MeSH
- hypoxanthinfosforibosyltransferasa chemie metabolismus MeSH
- hypoxanthiny chemie metabolismus farmakologie terapeutické užití MeSH
- infekce vyvolané Helicobacter pylori farmakoterapie patologie MeSH
- kinetika MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- organofosfonáty chemie metabolismus farmakologie terapeutické užití MeSH
- pentosyltransferasy chemie metabolismus MeSH
- prekurzory léčiv chemie metabolismus farmakologie terapeutické užití MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- simulace molekulární dynamiky MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antimicrobial peptides form part of the innate immune response and play a vital role in host defense against pathogens. Here we report a new antimicrobial peptide belonging to the cathelicidin family, cathelicidin-MH (cath-MH), from the skin of Microhyla heymonsivogt frog. Cath-MH has a single α-helical structure in membrane-mimetic environments and is antimicrobial against fungi and bacteria, especially Gram-negative bacteria. In contrast to other cathelicidins, cath-MH suppresses coagulation by affecting the enzymatic activities of tissue plasminogen activator, plasmin, β-tryptase, elastase, thrombin, and chymase. Cath-MH protects against lipopolysaccharide (LPS)- and cecal ligation and puncture-induced sepsis, effectively ameliorating multiorgan pathology and inflammatory cytokine through its antimicrobial, LPS-neutralizing, coagulation suppressing effects as well as suppression of MAPK signaling. Taken together, these data suggest that cath-MH is an attractive candidate therapeutic agent for the treatment of septic shock.
- MeSH
- antiinfekční látky chemie farmakologie MeSH
- fylogeneze MeSH
- kathelicidiny chemie farmakologie MeSH
- proteiny obojživelníků chemie farmakologie MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční seřazení MeSH
- sepse farmakoterapie MeSH
- žáby * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Familial inheritance in non-medullary thyroid cancer (NMTC) is an area that has yet to be adequately explored. Despite evidence suggesting strong familial clustering of non-syndromic NMTC, known variants still account for a very small percentage of the genetic burden. In a recent whole genome sequencing (WGS) study of five families with several NMTCs, we shortlisted promising variants with the help of our in-house developed Familial Cancer Variant Prioritization Pipeline (FCVPPv2). Here, we report potentially disease-causing variants in checkpoint kinase 2 (CHEK2), Ewing sarcoma breakpoint region 1 (EWSR1) and T-lymphoma invasion and metastasis-inducing protein 1 (TIAM1) in one family. Performing WGS on three cases, one probable case and one healthy individual in a family with familial NMTC left us with 112254 variants with a minor allele frequency of less than 0.1%, which was reduced by pedigree-based filtering to 6368. Application of the pipeline led to the prioritization of seven coding and nine non-coding variants from this family. The variant identified in CHEK2, a known tumor suppressor gene involved in DNA damage-induced DNA repair, cell cycle arrest, and apoptosis, has been previously identified as a germline variant in breast and prostate cancer and has been functionally validated by Roeb et al. in a yeast-based assay to have an intermediate effect on protein function. We thus hypothesized that this family may harbor additional disease-causing variants in other functionally related genes. We evaluated two further variants in EWSR1 and TIAM1 with promising in silico results and reported interaction in the DNA-damage repair pathway. Hence, we propose a polygenic mode of inheritance in this family. As familial NMTC is considered to be more aggressive than its sporadic counterpart, it is important to identify such susceptibility genes and their associated pathways. In this way, the advancement of personalized medicine in NMTC patients can be fostered. We also wish to reopen the discussion on monogenic vs polygenic inheritance in NMTC and instigate further development in this area of research.
- MeSH
- checkpoint kinasa 2 chemie genetika metabolismus MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci * MeSH
- genom lidský MeSH
- lidé MeSH
- papilární karcinom štítné žlázy genetika metabolismus MeSH
- protein EWS vázající RNA chemie genetika metabolismus MeSH
- protein TIAM1 chemie genetika metabolismus MeSH
- rodokmen MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- sekvenování celého genomu MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Itálie MeSH
Borrelia burgdorferi sensu lato (s.l.) is the etiological agent of Lyme disease, transmitted by ticks of the genus Ixodes Latreille. Diagnosis of Lyme disease in humans is often difficult and a detailed knowledge of the circulation of B. burgdorferi s.l. in tick hosts is therefore fundamental to support clinical procedures. Here we developed a molecular approach for the detection of B. burgdorferi s.l. in North Italian Ixodes ricinus (Linnaeus). The method is based on the amplification of a fragment of the groEL gene, which encodes a heat-shock protein highly conserved among B. burgdorferi s.l. species. The tool was applied in both qualitative and Real-time PCR approaches testing ticks collected in a North Italian area. The obtained results suggest that this new molecular tool could represent a sensitive and specific method for epidemiological studies aimed at defining the distribution of B. burgdorferi s.l. in I. ricinus and, consequently, the exposure risk for humans.
- MeSH
- bakteriální proteiny * analýza MeSH
- Borrelia burgdorferi komplex * genetika izolace a purifikace MeSH
- chaperon hsp60 * analýza MeSH
- klíště * mikrobiologie růst a vývoj MeSH
- kvantitativní polymerázová řetězová reakce * metody MeSH
- nymfa * mikrobiologie růst a vývoj MeSH
- sekvenční analýza proteinů MeSH
- sekvenční seřazení MeSH
- senzitivita a specificita MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Itálie MeSH
Morphological and molecular evaluation of tapeworms of the genus Bothriocephalus Rudolphi, 1808 (Cestoda: Bothriocephalidea), based on newly collected and uniformly fixed worms from freshwater fishes in Canada and the United States has revealed unexpected diversity. With a combination of selected morphological features and 4 molecular markers (18S rDNA V8 region, ITS1, ITS2, and COI gene sequences), the following morphotypes and lineages of the Bothriocephalus cuspidatus Cooper, 1917 complex were identified, several of which are specific to their respective fish definitive hosts and may represent separate species: B. cuspidatus sensu stricto from walleye, Sander vitreus (type host), which likely includes a miniature morphotype from Johnny darter, Etheostoma nigrum (both Percidae); Bothriocephalus morphotype from pumpkinseed, Lepomis gibbosus (Centrarchidae); and Bothriocephalus morphotype from rock bass, Ambloplites rupestris (Centrarchidae). The Bothriocephalus morphotype from goldeye, Hiodon alosoides (Hiodontidae), may also represent a separate lineage (possibly Bothriocephalus texomensisSelf, 1954) but requires additional studies. A morphotype from smallmouth bass, Micropterus dolomieu, based on a single specimen, is morphologically and genetically very similar to the morphotype from rock bass. Morphological study of the scolex and strobila of heat-killed and fixed specimens has revealed consistent differences, often subtle, that allowed us to differentiate between these morphotypes.
- MeSH
- Cestoda anatomie a histologie genetika ultrastruktura MeSH
- cestodózy parazitologie veterinární MeSH
- mikroskopie elektronová rastrovací veterinární MeSH
- nemoci ryb parazitologie MeSH
- okounovití parazitologie MeSH
- Perciformes parazitologie MeSH
- pravděpodobnostní funkce MeSH
- ribozomální DNA analýza chemie MeSH
- RNA ribozomální 18S genetika MeSH
- ryby MeSH
- sekvence nukleotidů MeSH
- sekvenční seřazení veterinární MeSH
- sladká voda MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kanada MeSH
- Spojené státy americké MeSH
Hexokinase (HXK) is the first key enzyme in the glycolytic pathway and plays an extremely important role in energy metabolism. By searching the microsporidian database, we found a sequence (NBO_27g0008) of Nosema bombycis Nägali, 1857 with high similarity to hexokinase-2, and named it as NbHXK2. The NbHXK2 gene has 894 bp and encodes 297 amino acids with 34.241 kD molecular weight and 5.26 isoelectric point. NbHXK2 contains 31 phosphorylation sites and 4 potential N-glycosylation sites with signal peptides and no transmembrane domain. Multiple sequence alignment showed that NbHXK2 shares more than 40% amino acid identity with that of other microsporidia, and the homology with hexokinase-2 of Nosema tyriae Canning, Curry, Cheney, Lafranchi-Tristem, Kawakami, Hatakeyama, Iwano et Ishihara, 1999, Nosema pyrausta (Paillot, 1927) and Nosema ceranae Fries, Feng, da Silva, Slemenda et Pieniazek, 1996 was 89.17%, 87.82% and 69.86%, respectively. Phylogenetic analysis based on the amino acid sequence of hexokinase showed that all microsporidia cluster together in the same clade, and are far away from animals, plants and fungi, and that N. bombycis is closely related to N. tyriae; N. pyrausta; N. ceranae and Nosema apis Zander, 1909. Immunolocalisation with the prepared polyclonal antibody showed that NbHXK2 was mainly distributed in the cytoplasm and plasmalemma in proliferative, sporulation stage and mature spore of N. bombycis. qRT-PCR assay showed that the NbHXK2 expressed at higher level during spore germination and at early stage of proliferation. These results indicate that N. bombycis may use its own glycolytic pathways to supply energy for infection and development, especially germination and in the early stage of proliferation, and acquire energy from the host through certain ways as well.
