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Až donedávna byl warfarin jediné antikoagulancium užívané v lékařské péči. Kvůli jeho četným nežádoucím účinkům, zejména různým druhům krvácení, byla vyvíjena nová orální antikoagulancia se stejnou nebo lepší bezpečností. Do současnosti bylo vyvinuto několik preparátů, a to přímé inhibitory trombinu (tzv. gatrany) a přímé inhibitory hemokoagulačního faktoru Xa (tzv. xabany). K prevenci CMP a jiných systémových embolizačních příhod u nemocných s fibrilací síní byly na základě velkých klinických studií zatím zaregistrovány následující látky (v pořadí, v němž jsou uvedeny): dabigatran, rivaroxaban a apixaban. Mají stejný nebo lepší bezpečnostní profil, ale i přes to je třeba je dlouhodobě epidemiologicky sledovat. Je také třeba více informací o zvládnutí pacientů s krvácením, protože vyjma dabigatranu nejsou schválená specifická antidota pro ostatní NOACs (NOvel Oral AntiCoagulantS). Ve výzkumu nových antikoagulancií se použil soubor pacientů z kardiologické ambulance užívající nová anti-koagulancia. Byly zjištěny jejich základní charakteristiky a sledovány zejména nežádoucí účinky. Dále bylo zkoumáno, zda výskyt nežádoucích účinků souvisí např. s věkem pacienta či skupinou BMI. Soubor obsahoval 150 pacientů, kteří byli rozděleni do tří skupin dle výše jmenovaných antikoagulancií. Základním cílem výzkumu bylo porovnání výskytu nežádoucích účinků mezi všemi třemi zmíněnými antikoagulanciemi. Statistická významnost byla nastavena na hladině 5 %. Z nových antikoagulans vykazovalo nejvíce krvácivých účinků Xarelto, za ním následovala Pradaxa a zcela bez krvácivých účinků byl Eliquis. Ostatní nežádoucí účinky, kam byly zařazeny gastrointestinální potíže, alergie a další, byly nejčastěji v případě Eliquis. Ve výskytu nežádoucích účinků nebyl mezi skupinami BMI, mezi pohlavími ani mezi jednotlivými věkovými skupinami zjištěn statisticky významný rozdíl. Této problematice je třeba se nadále věnovat. Pro validnější výsledky je třeba větší počet na dat, proto bude sběr dat pokračovat do konce roku 2017 a data budou znovu analyzována a vyhodnocena. Bude možno také uvést doporučení pro praxi.
Until recently, warfarin was the only anticoagulant used in medical care. Because of its numerous side effects, especially various types of bleeding, new oral anticoagulants have been developed with the same or better safety. To date, several preparations have been developed, direct thrombin inhibitors (so-called gatrans) and direct inhibitors of haemocoagulation factor Xa (so-called xabans). To prevent CMP and other systemic of embolization events in patients with atrial fibrillation, the following substances (in the order in which they are listed) have been registered as a result of large clinical trials: dabigatran, rivaroxaban and apixaban. They have the same or better safety profile, but they need to be monitored for epidemiological reasons over the long term. There is also a need for more information on managing patients with bleeding because, with the exception of dabigatran, a specific antidote for other NOACs (NOvel Oral AntiCoagulantS) is not approved. The study included patients from cardiology ambulance taking new anticoagulants. Their basic characteristics were identified and, in particular, the adverse effects were observed. It was further investigated whether the occurrence of adverse events was related, for example, to the age of the patient or to the BMI group. The group contained 150 patients, which were divided into three groups according to the above mentioned anticoagulants. The primary objective of the study was to compare adverse events between all three of these anticoagulants. Statistical significance was set at 5%. The most bleeding effects had Xarelto, followed by Pradaxa. Eliquis was completely bleeding-free. Other side effects that included gastrointestinal problems, allergies, and more were most common with Eliquis. There was no statistically significant difference between the BMI groups, among the sexes and between age groups in the occurrence of adverse events for each anticoagulants and theme. This issue needs to be further addressed. More data is required for more valid results, so data collection will continue until the end of this year and the data will be analyzed again and evaluated. Practice recommendations will also be given after this step.
It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS-controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane-bound enzymes (NOX1-5 and DUOX1-2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family member present in cyanobacteria, protists, plants, fungi, and the animal kingdom. We show that the calmodulin-like regulatory EF-domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C-terminal lobe of the EF-domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase (DH) domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the DH domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded-to-folded transition of the EF-domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation.
- MeSH
- konformace proteinů MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- molekulární modely MeSH
- NADPH-oxidasa 5 chemie genetika metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sinice enzymologie MeSH
- vápník metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The bread wheat (Triticum aestivum L.) genotype "Chinese Spring" ("CS") is the reference base in wheat genetics and genomics. Pericentric rearrangements in this genotype were systematically assessed by analyzing homoeoloci for a set of nonredundant genes from Brachypodium distachyon, Triticum urartu, and Aegilops tauschii in the CS chromosome shotgun sequence obtained from individual chromosome arms flow-sorted from CS aneuploid lines. Based on patterns of their homoeologous arm locations, 551 genes indicated the presence of pericentric inversions in at least 10 of the 21 chromosomes. Available data from deletion bin-mapped expressed sequence tags and genetic mapping in wheat indicated that all inversions had breakpoints in the low-recombinant gene-poor pericentromeric regions. The large number of putative intrachromosomal rearrangements suggests the presence of extensive structural differences among the three subgenomes, at least some of which likely occurred during the production of the aneuploid lines of this hexaploid wheat genotype. These differences could have significant implications in wheat genome research where comparative approaches are used such as in ordering and orientating sequence contigs and in gene cloning.
A set of 1160 minimum inhibitory concentration (MIC) values evaluating effect of substitution on the antimycobacterial activity of the previously published 2-(substituted benzyl)sulfanyl benzimidazoles, benzoxazoles, and benzothiazoles has been analyzed by the methods of multidimensional analysis (exploratory analysis, 2D-nonlinear mapping (NLM), principal component analysis (PCA), factor analysis (FA), multiple linear regression (MLR)). The antimycobacterial activity of 2-(subst. benzyl)sulfanyl derivatives of benzimidazole (BIM), 5-methylbenzimidazole (5-Me-BIM), benzoxazole (BOZ), and benzothiazole (BTZ) increased in the order of BTZ
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- benzimidazoly chemie farmakologie MeSH
- benzothiazoly chemie farmakologie MeSH
- benzoxazoly chemie farmakologie MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- mikrobiální testy citlivosti metody MeSH
- Mycobacterium avium účinky léků fyziologie MeSH
- Mycobacterium kansasii účinky léků fyziologie MeSH
- Mycobacterium tuberculosis účinky léků fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Quantification models based on the processing of FTIR spectra by partial least squares regression (PLS) were created in order to develop a method for the determination of 2-ethylhexyl nitrate (2-EHN) in diesel fuels. The set of standards was prepared using 2-EHN, biodiesel (FAME) and various mineral diesel fuels (2-EHN free). The standards were prepared in the concentration range of 2-EHN of 0-2436mgkg-1. The set of the standards was divided into the calibration, validation and test sets. While the calibration set was used to build the model, validation set was used in order to optimize the model parameters. The test set of the standards was used to assess the predictive ability and repeatability of the model. Several hundreds of various models were developed and compared in order to find a suitable combination of the preprocessing methods and number of latent variables. The most promising model was developed using mean centered spectra in the form of their first derivative and smoothed using Gap-Segment derivative. The model showed quite good predictive ability and repeatability.
In this study, various platinum cross-links in DNA bases were explored. Some of these structures occur in many cis/trans-platinated double-helixes or single-stranded adducts. However, in the models studied, no steric hindrance from sugar-phosphate backbone or other surroundings is considered. Such restrictions can change the bonding picture partially but hopefully the basic energy characteristics will not be changed substantially. The optimization of the structures explored was performed at the DFT level with the B3LYP functional and the 6-31G(d) basis set. Perturbation theory at the MP2/6-31++G(2df,2pd) level was used for the single-point energy and 6-31+G(d) basis set for the electron-property analyses. It was found that the most stable structures are the diguanine complexes followed by guanine-cytosine Pt-cross-links, ca 5 kcal mol(-1) less stable. The adenine-containing complexes are about 15 kcal mol(-1) below the stability of diguanine structures. This stability order was also confirmed by the BE of Pt-N bonds. For a detailed view on dative and electrostatic contributions to Pt-N bonds, Natural Population Analysis, determination of electrostatic potentials, and canonical Molecular Orbitals description of the examined systems were used.
Plant vascular meristems are sets of pluripotent cells that enable radial growth by giving rise to vascular tissues and are therefore crucial to plant development. However, the overall dynamics of cellular determination and patterning in and around vascular meristems is still unexplored. We study this process in the shoot vascular tissue of Arabidopsis thaliana, which is organized in vascular bundles that contain three basic cell types (procambium, xylem and phloem). A set of molecules involved in this process has now been identified and partially characterized, but it is not yet clear how the regulatory interactions among them, in conjunction with cellular communication processes, give rise to the steady patterns that accompany cell-fate determination and arrangement within vascular bundles. We put forward a dynamic model factoring in the interactions between molecules (genes, peptides, mRNA and hormones) that have been reported to be central in this process, as well as the relevant communication mechanisms. When a few proposed interactions (unverified, but based on related data) are postulated, the model reproduces the hormonal and molecular patterns expected for the three regions within vascular bundles. In order to test the model, we simulated mutant and hormone-depleted systems and compared the results with experimentally reported phenotypes. The proposed model provides a formal framework integrating a set of growing experimental data and renders a dynamic account of how the collective action of hormones, genes, and other molecules may result in the specification of the three main cell types within shoot vascular bundles. It also offers a tool to test the necessity and sufficiency of particular interactions and conditions for vascular patterning and yields novel predictions that may be experimentally tested. Finally, this model provides a reference for further studies comparing the overall dynamics of tissue organization and formation by meristems in other plant organs and species.
- MeSH
- algoritmy MeSH
- Arabidopsis cytologie genetika metabolismus MeSH
- biologické modely MeSH
- buněčná diferenciace MeSH
- cévní svazky rostlin cytologie genetika metabolismus MeSH
- cytokininy fyziologie MeSH
- genové regulační sítě MeSH
- meristém cytologie genetika metabolismus MeSH
- počítačová simulace MeSH
- proteinkinasy fyziologie MeSH
- proteiny huseníčku fyziologie MeSH
- regulace genové exprese u rostlin MeSH
- signální transdukce MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sex is a biological trait fundamental to the study of hominin fossils. Among the many questions that can be addressed are those related to taxonomy, biological variability, sexual dimorphism, paleoobstetrics, funerary selection, and paleodemography. While new methodologies such as paleogenomics or paleoproteomics can be used to determine sex, they have not been systematically applied to Pleistocene human remains due to their destructive nature. Therefore, we estimated sex from the coxal bone of the newly discovered pelvic remains of the Regourdou 1 Neandertal (Southwest France, MIS 5) based on morphological and metric data employing two methods that have been recently revised and shown to be reliable in multiple studies. Both methods calculate posterior probabilities of the estimate. The right coxal bone of Regourdou 1 was partially reconstructed providing additional traits for sex estimation. These methods were cross validated on 14 sufficiently preserved coxal bones of specimens from the Neandertal lineage. Our results show that the Regourdou 1 individual, whose postcranial skeleton is not robust, is a male, and that previous sex attributions of comparative Neandertal specimens are largely in agreement with those obtained here. Our results encourage additional morphological research of fossil hominins in order to develop a set of methods that are applicable, reliable, and reproducible.
- MeSH
- genomika MeSH
- Hominidae * MeSH
- lidé MeSH
- neandertálci * anatomie a histologie MeSH
- paleontologie MeSH
- zkameněliny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Francie MeSH
... 3 Interpolation and Extrapolation 110 -- 3.0 Introduction 110 -- 3.1 Preliminaries: Searching an Ordered ... ... 6.3 Exponential Integrals 266 -- 6.4 Incomplete Beta Function 270 -- 6.5 Bessel Functions of Integer Order ... ... 274 -- 6.6 Bessel Functions of Fractional Order, Airy Functions, Spherical -- Bessel Functions 283 - ... ... the Mth Largest 431 -- 8.6 Determination of Equivalence Classes 439 -- 9 Root Finding and Nonlinear Sets ... ... Simplex Method in Multidimensions 502 -- 10.6 Line Methods in Multidimensions 507 -- 10.7 Direction Set ...
3rd ed. xxi, 1235 s. : il. ; 27 cm + 1 CD-ROM
- MeSH
- matematické výpočty počítačové MeSH
- matematika MeSH
- numerická analýza pomocí počítače * MeSH
- Publikační typ
- monografie MeSH
In this work, the synthesis, characterization, and chiral capillary electrophoretic study of heptakis-(2,3-di-O-methyl-6-O-carboxymethyl)-β-CD (HDMCM), a single-isomer carboxymethylated CD, are presented. The pH-dependent and selector concentration-dependent enantiorecognition properties of HDMCM were investigated and discussed herein. The enantioseparation was assessed applying a structurally diverse set of noncharged, basic, and zwitterionic racemates. The increase in the selector concentration and gross negative charge of HDMCM improved the enantioseparation that could be observed in the majority of the cases. HDMCM was also successfully applied as BGE additive in NACE using a methanol-based system in order to prove the separation selectivity features and to highlight the broad applicability of HDMCM. Over 25 racemates showed partial or baseline separation with HDMCM under the conditions investigated, among which optimal enantiomer migration order was found for the four stereoisomers of tadalafil, tapentadol, and dapoxetine, offering the possibility of a chiral CE method development for chiral purity profiling of these drugs.
