SCA models
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Many patients with spinocerebellar ataxia (SCA) suffer from diverse neuropsychiatric issues, including memory impairments, apathy, depression, or anxiety. These neuropsychiatric aspects contribute per se to the reduced quality of life and worse prognosis. However, the extent to which SCA-related neuropathology directly contributes to these issues remains largely unclear. Behavioral profiling of various SCA mouse models can bring new insight into this question. This paper aims to synthesize recent findings from behavioral studies of SCA patients and mouse models. The role of SCA neuropathology for shaping psychiatric-like impairments may be exemplified in mouse models of SCA1. These mice evince robust cognitive impairments which are shaped by both the cerebellar as well as out-of-cerebellar pathology. Although emotional-related alternations are also present, they seem to be less robust and more affected by the specific distribution and character of the neuropathology. For example, cerebellar-specific pathology seems to provoke behavioral disinhibition, leading to seemingly decreased anxiety, whereas complex SCA1 neuropathology induces anxiety-like phenotype. In SCA1 mice with complex neuropathology, some of the psychiatric-like impairments are present even before marked cerebellar degeneration and ataxia and correlate with hippocampal atrophy. Similarly, complete or partial deletion of the implicated gene (Atxn1) leads to cognitive dysfunction and anxiety-like behavior, respectively, without apparent ataxia and cerebellar degeneration. Altogether, these findings collectively suggest that the neuropsychiatric issues have a biological basis partially independent of the cerebellum. As some neuropsychiatric issues may stem from weakening the function of the implicated gene, therapeutic reduction of its expression by molecular approaches may not necessarily mitigate the neuropsychiatric issues.
Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.
Objectives: To characterize the inclusion of cognition in definitions of successful aging (SA) according to empirical studies published in peer-reviewed journals.Methods: A systematic review across ISI Web of Knowledge.Results: Of the 74 included studies, there were 65 studies (87.8%) analyzing cognition as one component of multicomponent SA model (cognitive component studies), and 9 studies (12.2%) focusing solely on successful cognitive aging (SCA studies). Most of the studies operationalized cognition in SA by defining SA group and analyzing single SA indicators. A minority of the studies calculated the SA index. Finally, emergent techniques to operationalize SA as a latent variable and emergent field of cognition in SA in pathology were identified.Conclusions: The results highlight that cognition is being included in SA using different levels of complexity. Even though research investigating SA in pathology is emerging, there is currently a lack of utilization of the concept in pathological and at-risk populations.Clinical implications: The current research of cognition in SA provides several valid options to evaluate if a person is aging successfully. The emerging research indicates that people from at-risk and pathological populations can age successfully.
- MeSH
- kognice * MeSH
- kognitivní stárnutí * MeSH
- lidé MeSH
- stárnutí psychologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
The epithelial-mesenchymal plasticity, in tight association with stemness, contributes to the mammary gland homeostasis, evolution of early neoplastic lesions and cancer dissemination. Focused on cell surfaceome, we used mouse models of pre-neoplastic mammary epithelial and cancer stem cells to reveal the connection between cell surface markers and distinct cell phenotypes. We mechanistically dissected the TGF-β family-driven regulation of Sca-1, one of the most commonly used adult stem cell markers. We further provided evidence that TGF-β disrupts the lineage commitment and promotes the accumulation of tumor-initiating cells in pre-neoplastic cells.
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- ataxin-1 metabolismus MeSH
- epitelo-mezenchymální tranzice genetika MeSH
- epitelové buňky patologie MeSH
- experimentální nádory mléčných žláz genetika patologie MeSH
- lidé MeSH
- mléčné žlázy zvířat patologie MeSH
- myši MeSH
- nádorové buněčné linie transplantace MeSH
- nádorové kmenové buňky patologie MeSH
- nádory prsu genetika patologie MeSH
- plasticita buňky genetika MeSH
- receptor erbB-2 genetika MeSH
- regulace genové exprese u nádorů MeSH
- rekombinantní proteiny genetika metabolismus MeSH
- signální transdukce genetika MeSH
- transformující růstový faktor beta genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Deciphering the properties of adult stem cells is crucial for understanding of their role in healthy tissue and in cancer progression as well. Both stem cells and cancer stem cells have shown association with epithelial-to-mesenchymal transition (EMT) in various tissue types. Aiming to investigate the epithelial and mesenchymal phenotypic traits in adult mouse prostate, we sorted subpopulations of basal prostate stem cells (mPSCs) and assessed the expression levels of EMT regulators and markers with custom-designed gene expression array. The population of mPSCs defined by a Lin-/Sca-1+CD49fhi/Trop-2+ (LSC Trop-2+) surface phenotype was enriched in mesenchymal markers, especially EMT master regulator Slug, encoded by the Snai2 gene. To further dissect the role of Slug in mPSCs, we used transgenic Snai2tm1.1Wbg reporter mouse strain. Using this model, we confirmed the presence of mesenchymal traits and increase of organoid forming capacity in Slug+ population of mPSCs. The Slug+-derived organoids comprised all prostate epithelial cell types - basal, luminal, and neuroendocrine. Collectively, these data uncover the important role of Slug expression in the physiology of mouse prostate stem cells.
- MeSH
- epitelo-mezenchymální tranzice * MeSH
- epitelové buňky MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pohyb buněk MeSH
- prostata * MeSH
- rodina transkripčních faktorů Snail genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The sine-cosine algorithm (SCA) is a new population-based meta-heuristic algorithm. In addition to exploiting sine and cosine functions to perform local and global searches (hence the name sine-cosine), the SCA introduces several random and adaptive parameters to facilitate the search process. Although it shows promising results, the search process of the SCA is vulnerable to local minima/maxima due to the adoption of a fixed switch probability and the bounded magnitude of the sine and cosine functions (from -1 to 1). In this paper, we propose a new hybrid Q-learning sine-cosine- based strategy, called the Q-learning sine-cosine algorithm (QLSCA). Within the QLSCA, we eliminate the switching probability. Instead, we rely on the Q-learning algorithm (based on the penalty and reward mechanism) to dynamically identify the best operation during runtime. Additionally, we integrate two new operations (Lévy flight motion and crossover) into the QLSCA to facilitate jumping out of local minima/maxima and enhance the solution diversity. To assess its performance, we adopt the QLSCA for the combinatorial test suite minimization problem. Experimental results reveal that the QLSCA is statistically superior with regard to test suite size reduction compared to recent state-of-the-art strategies, including the original SCA, the particle swarm test generator (PSTG), adaptive particle swarm optimization (APSO) and the cuckoo search strategy (CS) at the 95% confidence level. However, concerning the comparison with discrete particle swarm optimization (DPSO), there is no significant difference in performance at the 95% confidence level. On a positive note, the QLSCA statistically outperforms the DPSO in certain configurations at the 90% confidence level.
- MeSH
- algoritmy * MeSH
- heuristika * MeSH
- počítačová simulace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cílem studie bylo ověřit psychometrické vlastnosti české verze Self-Curiosity Attitude-Interest Scale (SCAI-CZ) na výzkumném souboru českých vysokoškolských studentů, zjistit faktorovu strukturu a ověřit validitu a reliabilitu české verze nástroje. Zvídavost vůči sobě, kterou škála SCAI-CZ měří, je postojovou motivací jedinců k poznávání sebe samých a k odhalování nových aspektů svého psychického fungování. Studie proběhla na výzkumném souboru 296 studentů vysokých škol, 67 mužů a 229 žen, ve věku 18–24 let. K ověření faktorové struktury nástroje SCAI-CZ byla využita konfirmační faktorová analýza. Pro stanovení reliability byly využity koeficienty omega. Konfirmační faktorová analýza potvrdila dvoufaktorovou strukturu české verze nástroje SCAI-CZ. Reliabilita nástroje dosáhla uspokojivých hodnot. Faktory Postoj ke zvídavosti vůči sobě a Zvyšování povědomí o sobě spolu korelují níže, než jsme předpokládali. Souběžná i divergentní validita škály vyžaduje další ověření. Aplikační pole SCAI-CZ je jak ve výzkumné sféře, tak v psychoterapeutické praxi.
Self-curiosity concept has been defined relatively recently. Aschieri and Durosini (2015) understand it as a characteristic trait that expresses an individual's motivation to understand his inner world and his own psychological functioning and to discover new aspects of it. Self-curiosity is related to self-regulation activities, to general adaptability and to exploration of mindful feelin gs and sensations. The concept of curiosity and self-curiosity can be important in the field, when the work is based on self-understanding and internal motivation. In psychotherapy sessions, the client's inner motivation or his desire to understand himself / his problematic situation are often necessary for the progress in therapy. Some of therapeutic approaches enable clients to increase their curiosity and self-curiosity that are needed for adaptive behaviour ad a congruence. From the therapeutic point of view, the disposition of curiosity and self-curiosity is directly linked to the Satir model of family therapy. Higher levels of curiosity and self-curiosity in patient or client could be an advantage for him / her in therapy. In the case that the psychologist would know the client's level of curiosity in advance, the therapist could estimate the client's approach to therapy and interest in it better. Then, the consequence could be the appropriate choice of therapeutic tools. One of the methods for measuring the concept of curiosity towards oneself is the SCAI (Self-Curiosity Attitude-Interest Scale), constructed by Aschieri and Durosini, which has been recently translated into the Czech language. The purpose of this study was to verify basic psychometric properties of the Czech translation of the Self-Curiosity Attitude-Interest Scale (SCAI-CZ) in the sample of Czech university students. The aims were to verify the factor structure of the instrument and to explore both the convergent and divergent validity and relialibility of the scale. The research sample was consisted of 296 Czech university students; 67 male students and 229 female students, aged 18–24. Confirmatory factor analysis was used to verify the factor structure of the Self-Curiosity Attitude-Interest Scale. CFA confirmed two-factor structure of the Czech version of Self-Curiosity Attitude-Interest Scale with the factors Attitude toward Self-Curiosity and Interest in Increasing Knowledge of Self. Omega coefficients were used as the estimates of reliability. Data demonstrated satisfactory reliability considering the number of included items, coeficient omega reached 0,711 for whole scale, 0,666 for the factor Attitude toward Self-Curiosity and 0,763 for the factor Interest in Increasing Knowledge of Self, resp. Cronbach alpha reached 0,676 for the scale. The limits of the study are the use of Beck's BDI-II for the divergent validity and lower dependency of the factors within the sample of university students. As the conclusion, the results of the study are satisfactory for the use of the tool, the convergent and divergent validity of the scale will be subject of further investigation of the research team, especially for a sample of Czech adults.
- Klíčová slova
- Škála zvídavosti vůči sobě (SCAI-CZ),
- MeSH
- lidé MeSH
- mladý dospělý MeSH
- pátrací chování MeSH
- průzkumy a dotazníky MeSH
- psychiatrické posuzovací škály * MeSH
- psychometrie metody MeSH
- reprodukovatelnost výsledků MeSH
- sebepojetí MeSH
- sebezhodnocení (psychologie) MeSH
- statistika jako téma MeSH
- studenti psychologie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
Being implied in flight, mimetism, communication, and protection, the insect wings were crucial organs for the mega diversification of this clade. Despite several attempts, the problem of wing evolution remains unresolved because the basal parts of the veins essential for vein identification are hidden in the basivenal sclerites. The homologies between wing characters thus cannot be accurately verified, while they are of primary importance to solve long-standing problems, such as the monophyly of the Palaeoptera, viz. Odonatoptera, Panephemeroptera, and Palaeozoic Palaeodictyopterida mainly known by their wings. Hitherto the tools to homologize venation were suffering several cases of exceptions, rendering them unreliable. Here we reconstruct the odonatopteran venation using fossils and a new 3D imaging tool, resulting congruent with the concept of Riek and Kukalová-Peck, with important novelties, viz. median anterior vein fused to radius and radius posterior nearly as convex as radius anterior (putative synapomorphies of Odonatoptera); subcostal anterior (ScA) fused to costal vein and most basal primary antenodal crossvein being a modified posterior branch of ScA (putative synapomorphies of Palaeoptera). These findings may reveal critical for future analyses of the relationships between fossil and extant Palaeoptera, helping to solve the evolutionary history of the insects as a whole.
We previously demonstrated that predictive motor timing (i.e., timing requiring visuomotor coordination in anticipation of a future event, such as catching or batting a ball) is impaired in patients with spinocerebellar ataxia (SCA) types 6 and 8 relative to healthy controls. Specifically, SCA patients had difficulties postponing their motor response while estimating the target kinematics. This behavioral difference relied on the activation of both cerebellum and striatum in healthy controls, but not in cerebellar patients, despite both groups activating certain parts of cerebellum during the task. However, the role of these two key structures in the dynamic adaptation of the motor timing to target kinematic properties remained unexplored. In the current paper, we analyzed these data with the aim of characterizing the trial-by-trial changes in brain activation. We found that in healthy controls alone, and in comparison with SCA patients, the activation in bilateral striatum was exclusively associated with past successes and that in the left putamen, with maintaining a successful performance across successive trials. In healthy controls, relative to SCA patients, a larger network was involved in maintaining a successful trial-by-trial strategy; this included cerebellum and fronto-parieto-temporo-occipital regions that are typically part of attentional network and action monitoring. Cerebellum was also part of a network of regions activated when healthy participants postponed their motor response from one trial to the next; SCA patients showed reduced activation relative to healthy controls in both cerebellum and striatum in the same contrast. These findings support the idea that cerebellum and striatum play complementary roles in the trial-by-trial adaptation in predictive motor timing. In addition to expanding our knowledge of brain structures involved in time processing, our results have implications for the understanding of BG disorders, such as Parkinson disease where feedback processing or reward learning is affected.
- MeSH
- adaptace psychologická fyziologie MeSH
- bazální ganglia diagnostické zobrazování fyziologie patofyziologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- mozeček diagnostické zobrazování fyziologie patofyziologie MeSH
- neuropsychologické testy MeSH
- pohybová aktivita fyziologie MeSH
- spinocerebelární ataxie diagnostické zobrazování patofyziologie psychologie MeSH
- vnímání času fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.
- MeSH
- biologické modely MeSH
- buňky kostní dřeně cytologie MeSH
- celotělové ozáření * MeSH
- chimérismus * MeSH
- DNA metabolismus MeSH
- gastrointestinální trakt cytologie fyziologie MeSH
- hematopoetické kmenové buňky cytologie MeSH
- hematopoéza MeSH
- játra cytologie MeSH
- myši inbrední C57BL MeSH
- průtoková cytometrie MeSH
- regenerace * MeSH
- tenké střevo cytologie fyziologie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- transplantace kostní dřeně * MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH