• MeSH
• intrakraniální krvácení chemicky indukované   MeSH
• kojenec MeSH
• kombinované vakcíny škodlivé účinky   MeSH
• kompenzace a odškodnění MeSH
• lidé MeSH
• právní vědy MeSH
• rodina MeSH
• smrt MeSH
• vakcinace * škodlivé účinky   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• zprávy MeSH

x

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• MeSH
• difterie * prevence a kontrola   MeSH
• kombinované vakcíny farmakologie   terapeutické užití   MeSH
• lidé MeSH
• pertuse * prevence a kontrola   MeSH
• pertusová vakcína aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tetanus * prevence a kontrola   MeSH
• vakcína proti diftérii, tetanu a pertusi * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Multiple sex chromosomes usually arise from chromosomal rearrangements which involve ancestral sex chromosomes. There is a fundamental condition to be met for their long-term fixation: the meiosis must function, leading to the stability of the emerged system, mainly concerning the segregation of the sex multivalent. Here, we sought to analyze the degree of differentiation and meiotic pairing properties in the selected fish multiple sex chromosome system present in the wolf-fish Hoplias malabaricus (HMA). This species complex encompasses seven known karyotype forms (karyomorphs) where the karyomorph C (HMA-C) exhibits a nascent XY sex chromosomes from which the multiple X1X2Y system evolved in karyomorph HMA-D via a Y-autosome fusion. We combined genomic and cytogenetic approaches to analyze the satellite DNA (satDNA) content in the genome of HMA-D karyomorph and to investigate its potential contribution to X1X2Y sex chromosome differentiation. We revealed 56 satDNA monomers of which the majority was AT-rich and with repeat units longer than 100 bp. Seven out of 18 satDNA families chosen for chromosomal mapping by fluorescence in situ hybridization (FISH) formed detectable accumulation in at least one of the three sex chromosomes (X1, X2 and neo-Y). Nine satDNA monomers showed only two hybridization signals limited to HMA-D autosomes, and the two remaining ones provided no visible FISH signals. Out of seven satDNAs located on the HMA-D sex chromosomes, five mapped also to XY chromosomes of HMA-C. We showed that after the autosome-Y fusion event, the neo-Y chromosome has not substantially accumulated or eliminated satDNA sequences except for minor changes in the centromere-proximal region. Finally, based on the obtained FISHpatterns, we speculate on the possible contribution of satDNA to sex trivalent pairing and segregation.

• MeSH
• Characiformes * genetika   MeSH
• chromozom Y genetika   MeSH
• hybridizace in situ fluorescenční * MeSH
• karyotyp MeSH
• meióza genetika   MeSH
• molekulární evoluce MeSH
• pohlavní chromozomy * genetika   MeSH
• satelitní DNA * genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Předkládáme analýzu celogenomových dat izolátů Streptococcus pneumoniae sérotypů 8 a 22F izolovaných v České republice z invazivního pneumokokového onemocnění (IPO) v období 2014–2020. Proti těmto sérotypům působí nové vícevalentní pneumokokové konjugované vakcíny (PCV). Sérotypy 8 a 22F jsou co do četnosti na předních pozicích v působení IPO v České republice v recentním období. České izoláty S. pneumoniae byly porovnány se zahraničními izoláty ze stejného období a stejných sérotypů, které byly dostupné v mezinárodní databázi PubMLST. Materiál a metody: Pro studii byly vybrány izoláty z IPO v České republice z období 2014–2020 sérotypu 8 (22 izolátů) a sérotypu 22F (21 izolátů). Byla zvolena metoda celogenomová sekvenace (WGS), analýzy a vzájemné porovnání genomů proběhlo s využitím mezinárodní databáze PubMLST. Výsledky: Většina studovaných českých izolátů sérotypu 8 patří do dvou hlavních subpopulací. První subpopulace, ve které dominují izoláty ST-53, je součástí vysoce početné skupiny geneticky blízkých evropských i neevropských izolátů, které jsou na fylogenetické síti zřetelně odděleny. Druhá subpopulace českých izolátů sérotypu 8 (s dominancí ST-404) je geneticky variabilnější a na celosvětové fylogenetické síti tvoří samostatnou linii, v níž se nevyskytují žádné jiné evropské izoláty. České izoláty sérotypu 22F představují homogenní populaci s naprostou převahou ST-433, která patří do geneticky blízké evropské populace. Závěr: Analýza WGS dat izolátů z IPO sérotypů 8 a 22F poskytla detailní pohled na vzájemné genetické vztahy českých populací těchto sérotypů. Zároveň také umožnila porovnání českých populací s odpovídajícími populacemi z ostatních evropských i neevropských zemí. Získané výsledky prohlubují znalosti o šíření genetických linií působících IPO v České republice v postvakcinačním období a jsou podkladem ke zhodnocení vhodnosti zavedení nových vícevalentních PCV v České republice.

Aim: An analysis is presented of whole genome data of Streptococcus pneumoniae serotypes 8 and 22F isolated in the Czech Republic from invasive pneumococcal disease (IPD) in 2014–2020. New multivalent pneumococcal conjugate vaccines (PCVs) are effective against these serotypes. Recently, serotypes 8 and 22F have been among the leading causes of IPD in the Czech Republic. S. pneumoniae isolates from the Czech Republic were compared with those of the same serotypes recovered in other countries in the same period and available in the international database PubMLST. Material and methods: Isolates from IPD of serotypes 8 (22 isolates) and 22F (21 isolates) recovered in the Czech Republic in 2014–2020 were subjected to whole genome sequencing (WGS). The genomes were analysed and compared using the international database PubMLST. Results: Most of the studied Czech serotype 8 isolates belong to two main subpopulations. The first subpopulation, dominated by ST-53 isolates, is part of a highly abundant group of genetically close European and non-European isolates that are clearly separated on the phylogenetic network. The second subpopulation of Czech serotype 8 isolates (dominated by ST-404) is more genetically variable and forms a separate lineage on the global phylogenetic network, with no other European isolates. Czech isolates of serotype 22F are a homogeneous population with a clear predominance of ST-433, which belongs to a genetically close European population. Conclusion: The analysis of WGS data of IPD isolates of serotypes 8 and 22F provided a detailed insight into the genetic relationships between the Czech populations of these serotypes. It also allowed comparison of the Czech populations with the matched populations from other European and non-European countries. The obtained results add to the body of knowledge about the spread of genetic lineages causing IPD in the Czech Republic in the post-vaccination period and provide a basis for considering whether the use of the new multivalent PCVs in the Czech Republic would be beneficial.

• MeSH
• genom bakteriální MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• pneumokokové infekce epidemiologie   mikrobiologie   MeSH
• sekvenování celého genomu metody   MeSH
• séroskupina MeSH
• Streptococcus pneumoniae * genetika   izolace a purifikace   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

Bolivian hemorrhagic fever (BHF) caused by Machupo virus (MACV) is a New World arenavirus having a reported mortality rate of 25-35%. The BHF starts with fever, followed by headache, and nausea which rapidly progresses to severe hemorrhagic phase within 7 days of disease onset. One of the key promoters for MACV viral entry into the cell followed by viral propagation is performed by the viral glycoprotein (GPC). GPC is post-transcriptionally cleaved into GP1, GP2 and a signal peptide. These proteins all take part in the viral infection in host body. Therefore, GPC protein is an ideal target for developing therapeutics against MACV infection. In this study, GPC protein was considered to design a multi-epitope, multivalent vaccine containing antigenic and immunogenic CTL and HTL epitopes. Different structural validations and physicochemical properties were analysed to validate the vaccine. Docking and molecular dynamics simulations were conducted to understand the interactions of the vaccine with various immune receptors. Finally, the vaccine was codon optimised in silico and along with which immune simulation studies was performed in order to evaluate the vaccine's effectiveness in triggering an efficacious immune response against MACV.

• MeSH
• americká hemoragická horečka * imunologie   prevence a kontrola   MeSH
• arenaviry Nového světa imunologie   MeSH
• epitopy imunologie   chemie   MeSH
• lidé MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• virové vakcíny * imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• kombinované vakcíny MeSH
• lidé MeSH
• pertuse * diagnóza   epidemiologie   prevence a kontrola   MeSH
• pertusová vakcína MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, escape coronavirus disease 2019 therapeutics and vaccines, and jeopardize public health. To combat SARS-CoV-2 antigenic escape, we developed a rapid, high-throughput pipeline to discover monospecific VHH antibodies and iteratively develop VHH-Fc-VHH bispecifics capable of neutralizing emerging SARS-CoV-2 variants. By panning VHH single-domain phage libraries against ancestral or beta spike proteins, we discovered high-affinity VHH antibodies with unique target epitopes. Combining two VHHs into a tetravalent bispecific construct conferred broad neutralization activity against multiple variants and was more resistant to antigenic escape than the monospecific antibody alone. Following the rise of the Omicron variant, a VHH in the original bispecific construct was replaced with another VHH discovered against the Omicron BA.1 receptor binding domain; the resulting bispecific exhibited neutralization against both BA.1 and BA.5 sublineage variants. A heavy chain-only tetravalent VHH-Fc-VHH bispecific platform derived from humanized synthetic libraries held a myriad of unique advantages: (i) synthetic preconstructed libraries minimized risk of liabilities and maximized discovery speed, (ii) VHH scaffolds allowed for a modular "plug-and-play" format that could be rapidly iterated upon as variants of concern arose, (iii) natural dimerization of single VHH-Fc-VHH polypeptides allowed for straightforward bispecific production and purification methods, and (iv) multivalent approaches enhanced avidity boosting effects and neutralization potency, and conferred more robust resistance to antigenic escape than monovalent approaches against specific variants. This iterative platform of rapid VHH discovery combined with modular bispecific design holds promise for long-term viral control efforts.

• Publikační typ
• časopisecké články MeSH

In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.

• MeSH
• magnetická rezonanční spektroskopie MeSH
• magnetická rezonanční tomografie * metody   MeSH
• polymery * MeSH
• tkáňová distribuce MeSH
• voda MeSH
• železo MeSH
• Publikační typ
• časopisecké články MeSH

In the shadow of SARS-CoV-2, influenza seems to be an innocent virus, although new zoonotic influenza viruses evolved by mutations may lead to severe pandemics. According to WHO, there is an urgent need for better antiviral drugs. Blocking viral hemagglutinin with multivalent N-acetylneuraminic acid derivatives is a promising approach to prevent influenza infection. Moreover, dual inhibition of both hemagglutinin and neuraminidase may result in a more powerful effect. Since both viral glycoproteins can bind to neuraminic acid, we have prepared three series of amphiphilic self-assembling 2-thio-neuraminic acid derivatives constituting aggregates in aqueous medium to take advantage of their multivalent effect. One of the series was prepared by the azide-alkyne click reaction, and the other two by the thio-click reaction to yield neuraminic acid derivatives containing lipophilic tails of different sizes and an enzymatically stable thioglycosidic bond. Two of the three bis-octyl derivatives produced proved to be active against influenza viruses, while all three octyl derivatives bound to hemagglutinin and neuraminidase from H1N1 and H3N2 influenza types.

• MeSH
• chřipka lidská * farmakoterapie   MeSH
• hemaglutininové glykoproteiny viru chřipky metabolismus   MeSH
• hemaglutininy farmakologie   MeSH
• kyselina N-acetylneuraminová farmakologie   metabolismus   MeSH
• kyseliny neuraminové MeSH
• lidé MeSH
• neuraminidasa metabolismus   MeSH
• virus chřipky A, podtyp H1N1 * MeSH
• virus chřipky A, podtyp H3N2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Galectins are proteins of the family of human lectins. By binding terminal galactose units of cell surface glycans, they moderate biological and pathological processes such as cell signaling, cell adhesion, apoptosis, fibrosis, carcinogenesis, and metabolic disorders. The binding of monovalent glycans to galectins is usually relatively weak. Therefore, the presentation of carbohydrate ligands on multivalent scaffolds can efficiently increase and/or discriminate the affinity of the glycoconjugate to different galectins. A library of glycoclusters and glycodendrimers with various structural presentations of the common functionalized N-acetyllactosamine ligand was prepared to evaluate how the mode of presentation affects the affinity and selectivity to the two most abundant galectins, galectin-1 (Gal-1) and galectin-3 (Gal-3). In addition, the effect of a one- to two-unit carbohydrate spacer on the affinity of the glycoconjugates was determined. A new design of the biolayer interferometry (BLI) method with specific AVI-tagged constructs was used to determine the affinity to galectins, and compared with the gold-standard method of isothermal titration calorimetry (ITC). This study reveals new routes to low nanomolar glycoconjugate inhibitors of galectins of interest for biomedical research.

• MeSH
• galektiny * metabolismus   MeSH
• glykokonjugáty * farmakologie   chemie   MeSH
• lidé MeSH
• ligandy MeSH
• polysacharidy metabolismus   MeSH
• sacharidy chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH