A5041183160- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Neurological disorders and treatments
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Xenotransplantation and immune response
- DNA Repair Mechanisms
- Pancreatic function and diabetes
University of Helsinki
2022-2023
BOKU University
2021
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2012-2018
Charles University
2013-2018
Some promising treatments for Huntington's disease (HD) may require pre-clinical testing in large animals. Minipig is a suitable species because of its gyrencephalic brain and long lifespan.To generate HD transgenic (TgHD) minipigs encoding huntingtin (HTT)1-548 under the control human HTT promoter.Transgenesis was achieved by lentiviral infection porcine embryos. PCR assessment gene transfer, observations behavior, postmortem biochemical immunohistochemical studies were conducted.One copy...
Positive transcription elongation factor b (P-TEFb) is the crucial player in RNA polymerase II (Pol II) pause release that has emerged as a promising target cancer. Because single-agent therapy may fail to deliver durable clinical response, targeting of P-TEFb shall benefit when deployed combination therapy. We screened comprehensive oncology library and identified clinically relevant antimetabolites Mouse double minute 2 homolog (MDM2) inhibitors top compounds eliciting p53-dependent death...
<b><i>Background:</i></b> Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated (mtHtt) primarily causes degeneration of neurons brain, but it also affects peripheral tissues, including testes. <b><i>Objective:</i></b> We studied sperm and testes transgenic boars expressing N-terminal region human mtHtt. <b><i>Methods:</i></b> In this study, measures reproductive...
<b><i>Background:</i></b> Huntington disease (HD) is a fatal neurodegenerative disorder involving reduced muscle coordination, mental and behavioral changes, testicular degeneration. In order to further clarify the decreased fertility penetration ability of spermatozoa transgenic HD minipig boars (TgHD), we applied set mitochondrial metabolism (MM) parameter measurements this promising biological material, which can be collected noninvasively in longitudinal studies....
Abstract The transcription factors Cat8 and Sip4 were described in Saccharomyces cerevisiae Kluyveromyces lactis to have very similar DNA binding domains be necessary for derepression of a variety genes under non-fermentative growth conditions via the carbon source responsive elements (CSREs). methylotrophic yeast Komagataella phaffii (syn Pichia pastoris ) has two (TFs), which are putative homologs based on sequence similarity, termed Cat8-1 Cat8-2. It is yet unclear cellular processes they...
Testicular degeneration of Huntington9s disease involves the reduction germ cells and wall thickening seminiferous tubule. Since changes in ejaculates patients mammalians models has not yet been tested, aim our study was to analyse motility, amount, fertilising capacity mitochondrial function spermatozoa from two HD minipig boars F1 generation WT control animals 12 24 month age. Random analysis F2 at age 8 also performed. After semen collections transgenic boars, were prepared for vitro...
<h3>Background</h3> Large-animal minipig transgenic model of Huntington’s disease (HD), carrying N-terminal part human mutated huntingtin, was developed in Libechov and is expected to resemble clinical picture HD patients. Phenotyping this started immediately presymptomatic stage. Despite ongoing discussion, whether the glycolytic or mitochondrial metabolism (MM) crucial for sperm ATP production; we decided use spermatozoa as a promising biological material assess MM parameters HD....
<h3>Background</h3> Voice quality of patients with Huntington’s disease is commonly perceived as harsh, hoarse, or breathy. Digital signal analysis allows to quantify the degree hoarseness objectively by harmonic-to-noise ratio. Such a simple automated acoustic measurement could provide cheap, non-invasive, and effective biomarker disease. <h3>Aims</h3> The aim this study explore, whether presented in human well genetically modified minipig animal model <h3>Methods</h3> Data were digitally...
<h3>Background</h3> Huntington’s disease (HD) is characterised by involuntary chorea like movements, poor balance, slurred speech, difficulty swallowing, personality change and thinking manifesting in the middle age of patients. Changes behaviour, motor skills learning correlate with progression disease. Thus it necessary to monitor these changes new animal models. In 2009, we have generated transgenic minipigs (TgHD) expressing N-terminal (548 aa) part human huntingtin (Htt) containing 126...
Hunting for the cure Huntington´s disease (HD) requires extended pre-clinical studies to screen safety, tolerability and efficacy of potential therapeutic treatments. Therefore, large animal models were developed translational research human studies. The battery tests was designed monitoring phenotype similarity transgenic HD minipig model with patients. Motor cognitive functions monitored in group (tgHD) wild-type (wt) minipigs different ages 3 following years. results showed differences...
ABSTRACT Positive transcription elongation factor b (P-TEFb) is the crucial player in RNA polymerase II (Pol II) pause release that has emerged as a promising target cancer. Because single-agent therapy may fail to deliver durable clinical response, targeting of P-TEFb shall benefit when deployed combination therapy. We screened comprehensive oncology library and identified clinically relevant antimetabolites Mouse double minute 2 homolog (MDM2) inhibitors top compounds eliciting...