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Examination of the Spatial Structure of Pigs' Melanoma in Tissue Sections Based on Histology and Mass Spectrometry
Anýz, J.; Vysloužilová, L.; Horák, Vratislav; Štěpánková, O.; Vaculovič, T.; Adam, V.
2019 - English
We examine the spatial structure of the melanoma in tissue sections. The pigs melanoma was examined in 10 tissue samples obtained from animals of age between 4 and 22 weeks. The tissue sections were measured by light microscopy and Laser Ablation Ion Inductively Coupled Plasma Mass Spectrometry to obtain spatial metal (Cu, Zn) distribution. The exploratory analysis of the tissue sections indicates there is clearly a pattern in the spatial structure. Different projections of the spatial structure of the melanoma are obtained by the different measurement methods. The spectral clustering on the data was utilized to describe the structure in the data. According to the clustering results, there are distinct clusters of observations in the histological data. The spatial elemental distribution of the metals Cu and Zn cannot be clustered -the data form one compact cluster. The clustering of the histological images produces clusters which are related to the annotation of the biological samples in broader terms -the differences between fibrous and cancerous tissue.
Keywords:
MeLiM; melanoma
Available at various institutes of the ASCR
Examination of the Spatial Structure of Pigs' Melanoma in Tissue Sections Based on Histology and Mass Spectrometry
We examine the spatial structure of the melanoma in tissue sections. The pigs melanoma was examined in 10 tissue samples obtained from animals of age between 4 and 22 weeks. The tissue sections were ...
Phenotypic Analyses of the HD Transgenic Minipig Model (A11609)
Ellederová, Zdeňka
2018 - English
The transgenic Huntington's disease minipigs (TgHD) express N‐terminal part of human mutated huntingtin (124Q) under the control of human huntingtin promoter. The founder animal, born in 2009, gave birth to four subsequent generations with an equal contribution of wild‐type (WT) and transgenic (TgHD) piglets in all litters. The model is being used for preclinical huntingtin lowering studies. Here we take different non-invasive and invasive approaches, some of which are unique for large animal models, to study the phenotype development comparing WT and TgHD siblings. We show gradual progression of the disease in these TgHD animals. Moreover, some biomarkers were identified. These markers could serve for monitoring of organism response to HD treatment to assess efficacy and safety in preclinical studies prior to human clinical trials.
Keywords:
minipig
Available at various institutes of the ASCR
Phenotypic Analyses of the HD Transgenic Minipig Model (A11609)
The transgenic Huntington's disease minipigs (TgHD) express N‐terminal part of human mutated huntingtin (124Q) under the control of human huntingtin promoter. The founder animal, born in 2009, gave ...
Establishing preclinical proof-of-concept of gene therapy for Huntington disease
Miniariková, J.; Juhás, Štefan; Caron, N.; Spronck, L.; Vallés, A.; De Haan, M.; Blits, B.; Ellederová, Zdeňka; van Deventer, S.; Petry, H.; Southwell, A.; Déglon, N.; Motlík, Jan; Konstantinová, P.; Evers, M.
2017 - English
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. The translated expanded polyglutamine repeat in the huntingtin protein is known to cause toxic gain-of-function, affecting numerous cellular processes. Our approach involves a new therapeutic modality by developing a single (one-time) treatment for HD based on a gene therapy lowering the expression of the toxic huntingtin using the RNA interference (RNAi) mechanism. Huntingtin lowering is achieved using gene transfer of a cassette encoding an engineered microRNA targeting human HTT, delivered via adeno-associated viral vector serotype 5 (AAV5-miHTT).
Keywords:
Huntington´s disease
Available at various institutes of the ASCR
Establishing preclinical proof-of-concept of gene therapy for Huntington disease
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. The translated expanded polyglutamine repeat in the ...
Oxidative stress in primary porcine fibroblasts expressing mutated huntingtin
Šmatlíková, Petra; Askeland, G.; Vaškovičová, Michaela; Klíma, Jiří; Motlík, Jan; Eide, L.; Ellederová, Zdeňka
2017 - English
Molecular events, such as protein aggregation, mitochondrial dysfunction, and transcriptional dysregulation have been linked to Huntington’s disease (HD) pathogenesis. Oxidative stress has been considered as one of the key players in disease progression. Though, it is still not clear whether oxidative stress causes HD, or if it is a consequence of other primary events.
Keywords:
huntingtin
Available at various institutes of the ASCR
Oxidative stress in primary porcine fibroblasts expressing mutated huntingtin
Molecular events, such as protein aggregation, mitochondrial dysfunction, and transcriptional dysregulation have been linked to Huntington’s disease (HD) pathogenesis. Oxidative stress has been ...
Role of planar cell polarity pathway in ameloblastoma with focus on frizzled 6
Putnová, Barbora; Putnová, Iveta; Hrubá, Eva; Dosedělová, Hana; Štembírek, Jan; Daněk, Z.; Buchtová, Marcela
2017 - English
Ameloblastoma is the most common epithelial odontogenic tumour in the oral cavity. Its progression is usually slow and the surface is covered by an oral mucosa with physiologic appearance. These tumours do not cause any pain to the patient and therefore it is difficult to diagnose them on time and the first signs are often missed by clinician leading to late diagnosis.
Keywords:
ameloblastoma
Available at various institutes of the ASCR
Role of planar cell polarity pathway in ameloblastoma with focus on frizzled 6
Ameloblastoma is the most common epithelial odontogenic tumour in the oral cavity. Its progression is usually slow and the surface is covered by an oral mucosa with physiologic appearance. These ...
Results of the realisation of the experiments using large experimental animals – application of cells/ stem cells using different vectors, diagnostics
Juhás, Štefan; Juhásová, Jana
2017 - English
A design of methods to test application of cells/ stem cells using different vectors, solution of the application including diagnostics and connected agenda.
Keywords:
large animal models; stem cell therapy; spinal stem cells
Available at various institutes of the ASCR
Results of the realisation of the experiments using large experimental animals – application of cells/ stem cells using different vectors, diagnostics
A design of methods to test application of cells/ stem cells using different vectors, solution of the application including diagnostics and connected agenda.
Role of FGF signaling in zeugopod development
Buchtová, Marcela; Celá, Petra; Horáková, D.; Krejčí, P.
2017 - English
The fibroblast growth factor (FGF) signalling systém regulates many developmental processes including skeletogenesis, brain patterning, branching morphogenesis or limb development. as FGFs are key players in the variable processes of chondrogenesis, we experimentally manipulated this pathway to test its effect on zeugopode modeling.
Keywords:
FGF
Available at various institutes of the ASCR
Role of FGF signaling in zeugopod development
The fibroblast growth factor (FGF) signalling systém regulates many developmental processes including skeletogenesis, brain patterning, branching morphogenesis or limb development. as FGFs are key ...
Mechanism of complex tooth shape development in reptiles
Landová, Marie; Zahradníček, Oldřich; Dosedělová, Hana; Kavková, M.; Zikmund, T.; Buchtová, Marcela
2017 - English
Tooth shape formation in mammals is well known proces thanks to the broad studies on the mouse molars. The main role in regulation of this proces plays the enamel knot. Enamel knots are formed by cluster of cells, which serves as a source of numerous signalling molecules such as SHH or members of WNT, BMP and FGF families. Almost all our knowledge about teeth came from study on the mouse model. For better understanding of odontogenesis, it is however necessary to compare developmental processes to another species. One of the most heterogenic group of dentition type and shape are reptiles. How the shape of their teeth completed is still unknown. Aim of our study is therefore to uncover developmental processes involved in cusp formation in non-mammalian species with focus on reptiles. As model species for this study, we selected chameleons where multicuspis teeth develop in the caudal area of the jaw.
Keywords:
reptiles; tooth shape development
Available at various institutes of the ASCR
Mechanism of complex tooth shape development in reptiles
Tooth shape formation in mammals is well known proces thanks to the broad studies on the mouse molars. The main role in regulation of this proces plays the enamel knot. Enamel knots are formed by ...
Mitochondrial phenotype in minipig model transgenic for N-terminal part of human mutated huntingtin
Hansíková, H.; Rodinová, M.; Křížová, J.; Dosoudilová, Z.; Štufková, H.; Bohuslavová, Božena; Klíma, Jiří; Juhás, Štefan; Ellederová, Zdeňka; Motlík, Jan; Zeman, J.
2017 - English
Huntington’s disease (HD) is neurodegenerative disorder caused by an abnormal expansion of CAG repeat encoding a polyglutamine tract of huntingtin (htt). It has been postulated that mitochondria dysfunction may play significant role in the pathophysiology of the HD. But it is still not known yet in detail how mitochondria are able to cover energy needs of the cells during the progression of the HD.
Keywords:
minipig model; Huntington´s disease
Available at various institutes of the ASCR
Mitochondrial phenotype in minipig model transgenic for N-terminal part of human mutated huntingtin
Huntington’s disease (HD) is neurodegenerative disorder caused by an abnormal expansion of CAG repeat encoding a polyglutamine tract of huntingtin (htt). It has been postulated that mitochondria ...
Double strand DNA breaks response in Huntington´s disease
Šolc, Petr
2017 - English
There are strong evidences that DNA damage response (DDR) signalling significantly underline the molecular pathology of polyglutamine (polyQ) diseases, including Huntington´s disease (HD) [1-4]. Double strand DNA breaks (DSBs) are the most deleterious DNA lesions.\nIn this talk I will review how DDR on DSBs is affected in HD.\n
Keywords:
DNA damage response
Available at various institutes of the ASCR
Double strand DNA breaks response in Huntington´s disease
There are strong evidences that DNA damage response (DDR) signalling significantly underline the molecular pathology of polyglutamine (polyQ) diseases, including Huntington´s disease (HD) [1-4]. ...
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