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The role of proteostatic mechanisms in neurodegenerative diseases
Zezulová, Kristýna ; Vodička, Petr (advisor) ; Marková, Vendula (referee)
Protein homeostasis (proteostasis) plays an important role in maintaining normal cell function and viability. Neurons are particularly vulnerable to proteostasis dysregulation, resulting in damage, dysfunction, and neuronal death, as manifested in many neurodegenerative diseases. One of them is Huntington disease, hereditary neurodegeneration with autosomal dominant inheritance. Expansion of the CAG repeats in the huntingtin gene is translated into an abnormally long glutamine chain in huntingtin protein, leading to disruption of neuronal proteostasis. The primary affected area of the brain is the striatum of the basal ganglia. Disease is progressive, the onset of symptoms usually occurs in adulthood, and after many years leads to the death of the patient. Despite intensive research, disease pathology is still not fully understood, treatment is still only symptomatic and new studies, together with a deeper understanding, also raise many new questions. Through the complexity of the issue, the study of proteostasis in neurodegeneration can bring not only possible implications for therapy, but also could go deeper into the understanding of stress, memory or aging processes.
Comparison of Winter Biomass Burning Source Contribution at National Atmospheric Observatory Košetice Based on AMS and Aethalometer Data.
Schwarz, Jaroslav ; Vodička, Petr ; Zíková, Naděžda ; Mbengue, Saliou ; Šerfözö, Norbert ; Pokorná, Petra ; Makeš, Otakar ; Ždímal, Vladimír
Although atmospheric aerosol concentrations exhibit decreasing trend in last decades, the contribution of aerosol emitted by biomass combustion is opposite due to increasing wood combustion used for residential heating. Previous works determined that the share of aerosol of biomass burning origin was up to 50 % in winter. In this work, the data from aerosol mass spectrometer (AMS) and Positive Matrix Factorization (PMF) are used to elucidate biomass combustion aerosol impact at National Atmospheric Observatory Košetice (NAOK) and the results are compared with simple aethalometer model approach.
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On-line Measurements of Very Low Concentrations of EC/OC Aerosols at a Finish Sub-Arctic Backround Station.
Vodička, Petr ; Schwarz, Jaroslav ; Brus, David ; Ždímal, Vladimír
In this work, we tested the possibilities of an on-line Sunset Lab. EC/OC analyser during measurements when aerosol concentrations were close to detection limits declared by the manufacturer.
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Origin of Atmospheric Aerosol Based on Data with Different Time Resolution at the National Atmospheric Observatory Košetice.
Pokorná, Petra ; Zíková, Naděžda ; Lhotka, Radek ; Vodička, Petr ; Makeš, Otakar ; Mbengue, Saliou ; Holubová Šmejkalová, Adéla ; Schwarz, Jaroslav ; Ondráček, Jakub ; Ždímal, Vladimír
To improve the air quality the underlying causalities must be well understood,particularly when it comes to aspects such as PM concentration, sources and their origin. The aim of this work was to determine air pollution origin at NAOK based on atmospheric aerosol (AA) data of different time resolution measured during intensive summer campaing.
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Comparison of Atmospheric Aerosol Sources at Suburban and Rural Stations
Makeš, Otakar ; Schwarz, Jaroslav ; Vodička, Petr ; Ždímal, Vladimír
This article discusses source apportionment analysis of fine aerosol fraction measured by C-ToF AMS at two different sites. The result of the analysis is a comparison of the aerosol sources between suburban and background sites during summer and winter season.
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Characterization of Nitrogen Isotopic Composition in Fine Aerosol at a Central European Rural Background Station.
Vodička, Petr ; Kawamura, K. ; Schwarz, Jaroslav ; Kunwar, B. ; Ždímal, Vladimír
Studies of isotope ratios in atmospheric aerosols is relativelly new approach which can provide unique information on source emissions together with physical and chemical processes in the atmosphere (e.g. Kawamura et al., 2004). Here, we present seasonal variations in δ15N of total nitrogen (TN) in the PM1 fraction of atmospheric aerosols at a rural background site in Central Europe.\n
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MOCVD Iron Oxide Nanoparticle Generation not Only for Follow-Up Inalation Exposure Experiments.
Moravec, Pavel ; Schwarz, Jaroslav ; Vodička, Petr ; Kupčík, Jaroslav ; Švehla, Jaroslav
Iron oxide nanoparticles (NPs) are industrially produced and commercially available and they are also frequently emitted into the environment by iron making plants. In the human body, iron is maintained at homeostatic fairly low level. However, freshly generated iron oxide NPs cause febrile and inflammatory response known as metal fume fever, but the potential in vivo consequences of inhalation of iron oxide NPs from the atmosphere has not yet been investigated. An overview of recent studies evaluating iron oxide NPs cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity was presented by Valdiglesias et al. (2015). Toxicity of iron oxide NPs has been studied both in vitro and in vivo. Exposure chamber for the whole body inhalation experiments with small laboratory animals was constructed at the Institute of Analytical Chemistry of the CAS (Večeřa et al., 2011) and some methods of NPs generation for these experiments were already tested in our laboratory (Moravec et al., 2015. Moravec et al., 2016). In this study we tested a method of long lasting generation of iron oxide NPs by pyrolysis and oxidation of ironIII acetylacetonate (FeAA3).
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Comparison of Atmospheric Aerosol Volatility at a Rural Site in Central Europe.
Kubelová, Lucie ; Vodička, Petr ; Makeš, Otakar ; Zíková, Naděžda ; Ondráček, Jakub ; Schwarz, Jaroslav ; Ždímal, Vladimír
Volatility is an important characteristic of atmospheric aerosols as it affects their origin, lifetime and removal. Accurate description of aerosol volatilities is important for models calculating condensation of semi-volatile species and it also enables better identification of aerosol sources (Wu et al., 2009). However, our understanding of volatilities of organic atmospheric aerosols and the related processes is still rather poor (Han et al., 2016.
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Body fluid exosomes as potential carriers of Huntington’s disease biomarkers
Kupcová Skalníková, Helena ; Červenka, Jakub ; Bohuslavová, Božena ; Turnovcová, Karolína ; Vodička, Petr
Huntington’s disease (HD) is a hereditary neurodegenerative disorder characterized by a progressive motor, behavioural, and cognitive decline, ending in death. The cause of HD is an abnormal expansion of CAG repeats in HTT gene resulting in prolonged polyglutamine (polyQ) sequence in huntingtin protein (HTT). Huntingtin is a large protein (348 kDa) expressed ubiquitously through the body, with highest expression in the brain and testes. To study HD pathophysiology and to test experimental therapies, a transgenic HD minipig (TgHD) model expressing N-terminal part (N548-124Q) of human mutated huntingtin (mHTT) under the control of human huntingtin promoter was created in Libechov. Beside the mild neurological impairment, the TgHD boars show decreased fertility after 13th month of age.
Stimulating autophagy and reducing inclusions in mouse model of Huntington's disease via expression of transcription factor EB (TFEB)
Vodička, Petr ; Chase, K. ; Iulliano, M. ; Tousley, A. ; Valentine, D. T. ; Sapp, E. ; Kegel-Gleason, K. B. ; Sena-Esteves, M. ; Aronin, N. ; DiFiglia, M.
Mutant huntingtin (mHTT) is encoded by the Huntington’s disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy. We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7 mice using adeno-associated virus AAV2/9.

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8 Vodička, Pavel
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