Although Huntington's disease (HD) occurs only in humans, the use of animal models is crucial for HD research. New genetic models may provide novel insights into HD pathogenesis, but their relevance to human HD is problematic, particularly owing to a lower number of typically degenerated and dying striatal neurons and consequent insignificant reactive gliosis. Hence, neurotoxin-induced animal models are widely used for histopathological studies. Unlike in humans, the neurodegenerative process (NDP) of the HD phenotype develops very fast after the application of quinolinic acid (QA). For that reason, we compared three groups of rats in more advanced stages (1-12 months) of the QA lesion with 3 representative HD cases of varying length and grade. The outcomes of our long-term histological study indicate that significant parallels may be drawn between HD autopsies and QA-lesioned rat brains (particularly between post-lesional months 3 and 9) in relation to (1) the progression of morphological changes related to the neuronal degeneration, primarily the rarefaction of neuropil affecting the density as well as the character of synapses, resulting in severe striatal atrophy and (2) the participation of oligodendrocytes in reparative gliosis. Conversely, the development and character of reactive astrogliosis is principally conditioned by the severity of striatal NDP in the context of neuron-glia relationship. Despite the above-described differences, morphological patterns in which the components of striatal parenchyma react to the progression of NDP are similar in both human and rat brains. Our study specifies the possibilities of interpreting the morphological findings gained from the QA-induced animal model of HD in relation to HD post-mortem specimens.
- MeSH
- Nerve Degeneration pathology MeSH
- Gliosis pathology MeSH
- Huntington Disease pathology MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Brain pathology MeSH
- Oligodendroglia pathology MeSH
- Rats, Wistar MeSH
- Disease Progression MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Background: A large arteriovenous fistula (AVF) is a low-resistant circuit that affects organ perfusion and systemic hemodynamics even in standard conditions. The extent of its' effect in critical states has not been elucidated yet. We used norepinephrine to create systemic vasoconstriction, dobutamine to create high cardiac output, and rapid right ventricle pacing as a model of acute heart failure in a porcine model of high-flow AVF circulation. Methods: The protocol was performed on nine domestic female pigs under general anesthesia. AVF was created by connecting two high-diameter ECMO cannulas inserted in the femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Three interventions were performed-moderate dose of norepinephrine (0.25 ug/kg/min), moderate dose of dobutamine (10 ug/kg/min) and rapid right ventricle pacing to simulate low cardiac output state with mean arterial pressure under 60 mmHg. Measurements were taken with opened and closed arteriovenous fistula. Results: Continuous infusion of norepinephrine with opened AVF significantly increased mean arterial pressure (+20%) and total cardiac output (CO) (+36%), but vascular resistance remained virtually unchanged. AVF flow (Qa) rise correlated with mean arterial pressure increase (+20%; R = 0.97, p = 0.0001). Effective cardiac output increased, leading to insignificant improvement in organ perfusion. Dobutamine substantially increased cardiac output with insignificant effect on AVF flow and mean arterial pressure. Carotid artery blood flow increased significantly after dobutamine infusion by approximately 30%, coronary flow velocity increased significantly only in closed AVF state. The effective cardiac output using the heart failure model leading to decrease of carotid artery flow and worsening of brain and peripheral tissue oximetry. AVF blood flow also dropped significantly and proportionally to pressure, but Qa/CO ratio did not change. Therefore, the effective cardiac output decreased. Conclusion: In abovementioned extreme hemodynamic conditions the AVF flow was always directly proportional to systemic perfusion pressure. The ratio of shunt flow to cardiac output depended on systemic vascular resistance. These experiments highlight the detrimental role of a large AVF in these critical conditions' models.
- Publication type
- Journal Article MeSH
Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.
- MeSH
- Bacterial Proteins metabolism MeSH
- Cell Line MeSH
- Epithelial Cells microbiology MeSH
- Virulence Factors metabolism MeSH
- Host-Pathogen Interactions * MeSH
- Legionella pneumophila physiology MeSH
- Humans MeSH
- Macrophages microbiology MeSH
- Molecular Mimicry * MeSH
- Mice MeSH
- Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins metabolism MeSH
- Sequence Homology, Amino Acid MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Current knowledge of the genetic mechanisms underlying the inheritance of photosynthetic activity in forest trees is generally limited, yet it is essential both for various practical forestry purposes and for better understanding of broader evolutionary mechanisms. In this study, we investigated genetic variation underlying selected chlorophyll a fluorescence (ChlF) parameters in structured populations of Scots pine (Pinus sylvestris L.) grown on two sites under non-stress conditions. These parameters were derived from the OJIP part of the ChlF kinetics curve and characterize individual parts of primary photosynthetic processes associated, for example, with the exciton trapping by light-harvesting antennae, energy utilization in photosystem II (PSII) reaction centers (RCs) and its transfer further down the photosynthetic electron-transport chain. An additive relationship matrix was estimated based on pedigree reconstruction, utilizing a set of highly polymorphic single sequence repeat markers. Variance decomposition was conducted using the animal genetic evaluation mixed-linear model. The majority of ChlF parameters in the analyzed pine populations showed significant additive genetic variation. Statistically significant heritability estimates were obtained for most ChlF indices, with the exception of DI0/RC, φD0 and φP0 (Fv/Fm) parameters. Estimated heritabilities varied around the value of 0.15 with the maximal value of 0.23 in the ET0/RC parameter, which indicates electron-transport flux from QA to QB per PSII RC. No significant correlation was found between these indices and selected growth traits. Moreover, no genotype × environment interaction (G × E) was detected, i.e., no differences in genotypes' performance between sites. The absence of significant G × E in our study is interesting, given the relatively low heritability found for the majority of parameters analyzed. Therefore, we infer that polygenic variability of these indices is selectively neutral.
- MeSH
- Pinus sylvestris genetics physiology MeSH
- Chlorophyll physiology MeSH
- Fluorescence MeSH
- Photosynthetic Reaction Center Complex Proteins physiology MeSH
- Photosynthesis genetics MeSH
- Photosystem II Protein Complex physiology MeSH
- Genetic Variation * MeSH
- Genotype * MeSH
- Quantitative Trait, Heritable * MeSH
- Forests MeSH
- Genes, Plant MeSH
- Trees genetics physiology MeSH
- Light MeSH
- Electron Transport MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... (Voldřich) • 101 -- Praktický význam otisků a modelů, jejich názvosloví 101 -- Otisky a jejich technika ... ... hmotou — odlévání otisků 123 -- Konečná úprava modelů 125 -- Podrobné otisky a modely — nepřímý postup ... ... -- Celkový přehled práce při nepřímém postupu 126 -- Podrobný otisk 127 -- Zhotovování podrobných modelů ... ... 00 00 10 10 00 co co co co co co co -- ^^ ^ ^ ^ ^^ -- AA -- 00 00 00 00 00 -- 1 O OA -- Zhotovení modelů ... ... v laboratoři 544 -- Úprava modelů 546 -- Stanovení čelistních vztahů 546 -- Metody ke zjištění výšky ...
3. přeprac. a dopl. vyd. 699 s. : il., tab. ;25 cm
- MeSH
- Prosthodontics MeSH
- Conspectus
- Stomatologie
- NML Fields
- zubní lékařství
- NML Publication type
- kolektivní monografie
... Farmakokinetický model 162 -- 5.2.2. Koncentrační vztahy a biologická dostupnost 164 -- 5.2.3. ... ... Jakost, jištění jakosti (Quality Assurance - QA) -- 10.3.2. ...
3., přeprac. a dopl. vyd. xv, 399 s. : il., tab. ; 29 cm
Kniha je koncipována především jako učebnice. Seznamuje čtenáře s aktualizovanou náplní oboru farmaceutická technologie - galenická farmacie. Stěžejním materiálem je nejen pro studenty farmaceutických fakult, ale i pro jiné odborné pracovníky ve farmaceutické výrobě a přípravě léčiv ve zdravotnických zařízeních. Třetí vydání publikace odráží nové legislativní požadavky, které se v oblasti farmacie po vstupu do EU zaměřují především na výrobu, přípravu, kontrolu a používání účinnějších a bezpečnějších léčiv.
- Conspectus
- Farmacie. Farmakologie
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- farmacie a farmakologie
- farmacie a farmakologie
- NML Publication type
- učebnice vysokých škol
... znečištění ovzduší 247 -- 10.5.1 Typy modelů 247 -- 10.5.2 Základní vztahy 251 -- 10.5.3 Rovnice difúze ... ... 251 -- 10.5.4 Gaussovské disperzní modely 252 -- 10.5.5 Vlečkové modely 256 -- 10.5.6 Puff modely 257 ... ... 297 -- 12.4.2 Výstupy klimatických modelů 301 -- 12.4.3 Zvětšení rozlišení 302 -- 12.4.4 Pokusy prováděné ... ... atmosférických srážek 311 -- 12.6 Změny klimatu v ČR 315 -- 12.6.1 Variantní scénáře založené na výstupech modelů ... ... a ECHAM4 316 -- 12.6.2 Scénáře založené na HadCM3 318 -- 12.6.3 Využití regionálních klimatických modelů ...
1. elektronické vydání 1 online zdroj (352 stran)
Publikace, na níž se podílel tým předních českých odborníků na životní prostředí, se věnuje problematice atmosféry, klimatu a kvality ovzduší v širokých souvislostech, jež přesahují pouhý přírodovědný pohled. K chemickým, fyzikálním charakteristikám ovzduší a k jejich dynamice promlouvají v dobách proměn globálního klimatu a emisí toxických látek do ovzduší měst a průmyslových aglomerací nejen přírodovědci, ale i ekonomové, politici a laická veřejnost. V obsáhlé učebnici o aktuálním stavu klimatu se proto setkávají specializované kapitoly od autorů s různým odborným zázemím. Cílem editorů bylo umožnit čtenářům zaměřit se na jednotlivé části podle jejich zájmu a potřeby, ohled je přitom brán zejména na studenty a odbornou veřejnost bez hlubších znalostí v oborech fyziky, chemie či matematiky. Kniha probírá důležité aspekty znečištění ovzduší a pomáhá pochopit principy jevů a dějů v zemské atmosféře, klimatické změny a problematiku ochrany atmosféry v globálním kontextu, včetně ekologické politiky v praxi.
Regulatory T cells (Tregs) play a key role in the peripheral self-tolerance and preventing autoimmunity. While classical CD4+ Foxp3+ Tregs are well established, their CD8+ counterparts are still controversial in many aspects including their phenotypic identity and their mechanisms of suppression. Because of these controversies and because of only a limited number of studies documenting the immunoregulatory function of CD8+ Tregs in vivo, the concept of CD8+ Tregs is still not unanimously accepted. We propose that any T-cell subset considered as true regulatory must be distinguishable from other cell types and must suppress in vivo immune responses via a known mechanism. In this article, we revisit the concept of CD8+ Tregs by focusing on the characterization of individual CD8+ T-cell subsets with proposed regulatory capacity separately. Therefore, we review the phenotype and function of CD8+ FOXP3+ T cells, CD8+ CD122+ T cells, CD8+ CD28low/- T cells, CD8+ CD45RClow T cells, T cells expressing CD8αα homodimer and Qa-1-restricted CD8+ T cells to show whether there is sufficient evidence to establish these subsets as bona fide Tregs. Based on the intrinsic ability of CD8+ Treg subsets to promote immune tolerance in animal models, we elaborate on their potential use in clinics.
- MeSH
- CD28 Antigens immunology MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Phenotype MeSH
- Immune Tolerance immunology MeSH
- Humans MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- T-Lymphocyte Subsets immunology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Understanding the net photosynthesis of plant canopies requires quantifying photosynthesis in challenging environments, principally due to the variable light intensities and qualities generated by sunlight interactions with clouds and surrounding foliage. The dynamics of sunflecks and rates of change in light intensity at the beginning and end of sustained light (SL) events makes photosynthetic measurements difficult, especially when dealing with less accessible parts of plant foliage. High time resolved photosynthetic monitoring from pulse amplitude modulated (PAM) fluorometers has limited applicability due to the invasive nature of frequently applied saturating flashes. An alternative approach used here provides remote (<5 m), high time resolution (10 s), PAM equivalent but minimally invasive measurements of photosynthetic parameters. We assessed the efficacy of the QA flash protocol from the Light-Induced Fluorescence Transient (LIFT) technique for monitoring photosynthesis in mature outer canopy leaves of potted Persea americana Mill. cv. Haas (Avocado) trees in a semi-controlled environment and outdoors. Initially we established that LIFT measurements were leaf angle independent between ±40° from perpendicular and moreover, that estimates of 685 nm reflectance (R685) from leaves of similar chlorophyll content provide a species dependent, but reasonable proxy for incident light intensity. Photosynthetic responses during brief light events (≤10 min), and the initial stages of SL events, showed similar declines in the quantum yield of photosystem II (ΦII) with large transient increases in 'constitutive loss processes' (ΦNO) prior to dissipation of excitation by non-photochemical quenching (ΦNPQ). Our results demonstrate the capacity of LIFT to monitor photosynthesis at a distance during highly dynamic light conditions that potentially may improve models of canopy photosynthesis and estimates of plant productivity. For example, generalized additive modelling performed on the 85 dynamic light events monitored identified negative relationships between light event length and ∆ΦII and ∆electron transport rate using either ∆photosynthetically active radiation or ∆R685 as indicators of leaf irradiance.
- MeSH
- Chlorophyll MeSH
- Fluorescence MeSH
- Photosynthesis physiology MeSH
- Plant Leaves physiology MeSH
- Persea physiology MeSH
- Trees physiology MeSH
- Light MeSH
- Remote Sensing Technology instrumentation methods MeSH
- Models, Theoretical MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... Holmes 232 -- Monkey models for AIDS research, G. ... ... Cotter 248 -- Monkey models for AIDS research, G. ... ... Gluckman 323 -- Transgenic animals: a model for studying the molecular biology of hepatitis ? ... ... Hardcastle 361 -- The rat as a model organism in human biomedical research, G. ... ... Goodfellow 683 -- A transgenic rat model for Alzheimer’s disease, D. ...
Biomedical and health research, ISSN 0929-6743 vol. 9
xxxix, 744 s. ; 24 cm
- Conspectus
- Veřejné zdraví a hygiena
- NML Fields
- veřejné zdravotnictví
- politologie, politika, zdravotní politika