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Opis: Tau is natively an unfolded protein that promotes the assembly and the stability of the axonal microtubules in the central nervous system. Increased formation of Tau protein aggregates has been causatively implicated in several neurodegenerative diseases called tauopathies. In the present study, we used the Drosophila melanogaster system to express the longest isoform of human Tau (2N4R) in the nervous system of adult flies, recreating the main features of the human pathology. Herein, this Tau-mediated neurodegeneration model was used as a platform to perform genetic screenings to identify putative modifiers of Tau toxicity. Our strategy exploited the modulation of genes considered as risk factors of Alzheimer’s disease (AD), Frontotemporal Dementias and other neurodegenerative diseases by RNA interference in vivo. This approach allowed us to identify a new gene which participates in the neuronal response against Tau induced neurotoxicity in Drosophila: D-Reep1, homologue of human REEP1 gene (h-Reep1). D-Reep1 knockout flies showed no apparent phenotypes in physiological growing and developmental conditions, however, they showed peculiar sensitivity to stress conditions. In addition, D-Reep1 knockout enhanced the neurodegeneration mediated by Tau expression in Drosophila eyes. On the contrary, the overexpression of UAS-D-Reep1 and UAS-h-Reep1 abolished the typical rough eye phenotype induced by the presence of Tau. The Co-expression of D-Reep1 in Tau backgrounds did not alter the phosphorylation pattern of this protein while, the presence of D-Reep1 seemed to prevent the formation of Tau aggregates in vivo. Thus, the data support the idea that D-Reep1 exerts a protective role on Tau induced toxicity which is independent of its phosphorylation status. In this work, I analysed the mechanisms behind the neuroprotective role of D-Reep1 and, in particular, I found that REEP1 is involved in the regulation of the unfolded protein response (UPR) through the PERK-ATF4 cascade within the ER. By the activation of this pathway, the neurotoxic aggregates of Tau are removed from Drosophila neuronal tissues rescuing the normal characteristics of the affected tissues. Evidences also suggest that the activation of autophagy was behind the removal of Tau aggregates, providing new molecular information about the physiological role of D Reep1 in the nervous system.
Ključne besede: AD Alzheimer Disease APP Amyloid precursor protein CNS Central Nervous System DM Drosophila melanogaster HSP Hereditary Spastic Paraplegia LN Lewy’s neurite MT Microtubule MAP Microtubule associated protein MT Microtubule/s MTBD Microtubule binding domain NFT Neurofibrillary tangle NP Neuritic plaques PHF Paired helical filament PS1 Presenilin 1 PS2 Presenilin 2 SPG Spastic Paraplegia ThS Thioflavin S
Objavljeno v RUNG: 06.12.2019; Ogledov: 4660; Prenosov: 124
Celotno besedilo (2,59 MB)

Opis: In June 2006, two perfluorocarbon tracer experiments were conducted in central Manchester UK as part of the CityFlux campaign. The main aim was to investigate vertical dispersion in an urban area during convective conditions, but dispersion mechanisms within the street network were also studied. Paired receptors were used in most cases where one receptor was located at ground level and one at roof level. One receptor was located on the roof of Portland Tower which is an 80m high building in central Manchester. Source receptor distances in the two experiments varied between 120 and 600 m. The results reveal that maximum concentration was sometimes found at roof level rather than at ground level implying the effectiveness of convective forces on dispersion. The degree of vertical dispersion was found to be dependent on source receptor distance as well as on building height in proximity to the release site. Evidence of flow channelling in a street canyon was also found. Both a Gaussian profile and a street network model were applied and the results show that the urban topography may lead to highly effective flow channelling which therefore may be a very important dispersion mechanism should the right meteorological conditions prevail. The experimental results from this campaign have also been compared with a simple urban dispersion model that was developed during the DAPPLE framework and show good agreement with this. The results presented here are some of the first published regarding vertical dispersion. More tracer experiments are needed in order to further characterise vertical concentration profiles and their dependence on, for instance, atmospheric stability. The impact of urban topography on pollutant dispersion is important to focus on in future tracer experiments in order to improve performance of models as well as for our understanding of the relationship between air quality and public health.
Ključne besede: air quality, atmospheric chemistry, concentration (composition), convective system, dispersion, public health, street canyon, tracer, urban area
Objavljeno v RUNG: 18.07.2019; Ogledov: 4203; Prenosov: 0
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Opis: ∂13C values of a suite of halocarbons have been determined in an urban background site in Bristol, UK. A novel mobile preconcentration system, based on the use of multi-adsorbent sample tubes, has been developed for trapping relatively large-volume air samples in potentially remote areas. An Adsorption Desorption System-Gas Chromatography-Electron Capture Detector was used to measure the mixing ratios of the selected halocarbon species, while a Gas ChromatographyCombustionIsotope Ratio Mass Spectrometer was used to determine ∂13C values. For the species with strong local sources, the variation of isotope ratios has been observed over the experimental period. Some of the results reported in the present study differ from previously reported values and reasons for this are discussed. The reporting of different ∂13C values for selected halocarbons from different areas in the present study suggests that ∂13C values may be used to determine the relative magnitudes of anthropogenic and biogenic sources.
Ključne besede: Adsorption Desorption System (ADS), Automated Thermal Desorber (ATD), Electron Capture Detector (ECD), Gas Chromatography (GC), Isotope Ratio Mass Spectrometry (IRMS)
Objavljeno v RUNG: 18.07.2019; Ogledov: 4490; Prenosov: 0
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Opis: In the last few decades, the Modern Conservation Movement has developed from European-limited practices into a global movement with universal common views and practical measures for managing heritage resources in different cultural contexts. As an innovative idea of this movement, the Historic Urban Landscape approach aims to protect and manage historic urban environments with respect to both the fundamental principles in the international doctrines and the local social/cultural/historical contexts. It recommends local authorities to use the HUL toolkit to identify, conserve and manage the overall landscape of their historic cities. In the case of China, who is an old civilization, a modern nation and a socialist country at the same time, the conservation practice needs to follow the basic and common conservation principles in the international doctrines, and meanwhile, it shall make its initiatives based on the actual social, cultural and political situations. The establishment of Historically and Culturally Famous City (HCF City in short) system is a positive attempt for such a purpose. The system manages various urban elements relating to the city’s historical and cultural features under a comprehensive notion of HCF City. However, the system is not prefect because it depends excessively on the top-down management of local governments, and also because it overlooks the spatial and spiritual relationships among the protected elements... The thesis provides a big picture of architectural and urban conservation practices in China. It introduces the forming process and the characteristics of historic urban fabric, as well as the history of urban conservation. Then, it takes a deep look at the existing HCF City system, including its basic ideas, structures and mechanism. It analyses the system’s initiatives and deficiencies. Finally, it provides feasible advices to improve the current system by using the HUL toolkit.
Ključne besede: Urban, History, Heritage, Conservation, Management International Principles, Modern Conservation Movement, Globalization, Localization Historic Urban Area, Historically and Culturally Famous Cities, Conservation System, Historic Urban Landscape Chinese Architecture, Chinese Urban Planning, Conservation History, Policy
Objavljeno v RUNG: 11.02.2019; Ogledov: 7206; Prenosov: 83
Celotno besedilo (217,96 MB)

Ključne besede: adult education, teaching practices, higher education, Slovene education system, quality assurance
Objavljeno v RUNG: 18.01.2018; Ogledov: 5169; Prenosov: 0
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