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  1. Article ; Online: The searching for agents for Alzheimer's disease treatment via the system of self-consistent models.

    Toropov, Andrey A / Toropova, Alla P / Achary, P Ganga Raju / Raškova, Maria / Raška, Ivan

    Toxicology mechanisms and methods

    2022  Volume 32, Issue 7, Page(s) 549–557

    Abstract: Robust quantitative structure-activity relationships (QSARs) for hBACE-1 inhibitors (pIC50) for a large database ( ...

    Abstract Robust quantitative structure-activity relationships (QSARs) for hBACE-1 inhibitors (pIC50) for a large database (
    MeSH term(s) Alzheimer Disease/drug therapy ; Humans ; Molecular Structure ; Monte Carlo Method ; Quantitative Structure-Activity Relationship ; Software
    Language English
    Publishing date 2022-04-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2081252-8
    ISSN 1537-6524 ; 1537-6516 ; 1051-7235
    ISSN (online) 1537-6524
    ISSN 1537-6516 ; 1051-7235
    DOI 10.1080/15376516.2022.2053918
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  2. Article: The sequence of amino acids as the basis for the model of biological activity of peptides.

    Toropova, Alla P / Raškova, Maria / Raška, Ivan / Toropov, Andrey A

    Theoretical chemistry accounts

    2021  Volume 140, Issue 2, Page(s) 15

    Abstract: The algorithm of building up a model for the biological activity of peptides as a mathematical function of a sequence of amino acids is suggested. The general scheme is the following: The total set of available data is distributed into the active ... ...

    Abstract The algorithm of building up a model for the biological activity of peptides as a mathematical function of a sequence of amino acids is suggested. The general scheme is the following: The total set of available data is distributed into the active training set, passive training set, calibration set, and validation set. The training (both active and passive) and calibration sets are a system of generation of a model of biological activity where each amino acid obtains special correlation weight. The numerical data on the correlation weights calculated by the Monte Carlo method using the CORAL software (http://www.insilico.eu/coral). The target function aimed to give the best result for the calibration set (not for the training set). The final checkup of the model is carried out with data on the validation set (peptides, which are not visible during the creation of the model). Described computational experiments confirm the ability of the approach to be a tool for the design of predictive models for the biological activity of peptides (expressed by pIC50).
    Language English
    Publishing date 2021-01-22
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1463180-5
    ISSN 1432-2234 ; 1432-881X
    ISSN (online) 1432-2234
    ISSN 1432-881X
    DOI 10.1007/s00214-020-02707-8
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  3. Article ; Online: Alternative isoforms of KDM2A and KDM2B lysine demethylases negatively regulate canonical Wnt signaling.

    Lađinović, Dijana / Pinkas, Daniel / Šopin, Tijana / Raška, Otakar / Liška, František / Raška, Ivan / Vacík, Tomáš

    PloS one

    2020  Volume 15, Issue 10, Page(s) e0236612

    Abstract: A precisely balanced activity of canonical Wnt signaling is essential for a number of biological processes and its perturbation leads to developmental defects or diseases. Here, we demonstrate that alternative isoforms of the KDM2A and KDM2B lysine ... ...

    Abstract A precisely balanced activity of canonical Wnt signaling is essential for a number of biological processes and its perturbation leads to developmental defects or diseases. Here, we demonstrate that alternative isoforms of the KDM2A and KDM2B lysine demethylases have the ability to negatively regulate canonical Wnt signaling. These KDM2A and KDM2B isoforms (KDM2A-SF and KDM2B-SF) lack the N-terminal demethylase domain, but they still have the ability to bind to CpG islands in promoters and to interact with their protein partners via their other functional domains. We have observed that KDM2A-SF and KDM2B-SF bind to the promoters of axin 2 and cyclin D1, two canonical Wnt signaling target genes, and repress their activity. Moreover, KDM2A-SF and KDM2B-SF are both able to strongly repress a Wnt-responsive luciferase reporter. The transcriptional repression mediated by KDM2A-SF and KDM2B-SF, but also by KDM2A-LF, is dependent on their DNA binding domain, while the N-terminal demethylase domain is dispensable for this process. Surprisingly, KDM2B-LF is unable to repress both the endogenous promoters and the luciferase reporter. Finally, we show that both KDM2A-SF and KDM2B-SF are able to interact with TCF7L1, one of the transcriptional mediators of canonical Wnt signaling. KDM2A-SF and KDM2B-SF are thus likely to negatively affect the transcription of canonical Wnt signaling target genes by binding to their promoters and by interacting with TCF7L1 and other co-repressors.
    MeSH term(s) CpG Islands ; Cyclin D1/genetics ; Cyclin D1/metabolism ; F-Box Proteins/genetics ; F-Box Proteins/metabolism ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine/genetics ; Lysine/metabolism ; Promoter Regions, Genetic ; Protein Isoforms ; Transcription Factor 7-Like 1 Protein/genetics ; Transcription Factor 7-Like 1 Protein/metabolism ; Wnt Signaling Pathway
    Chemical Substances CCND1 protein, human ; F-Box Proteins ; Protein Isoforms ; TCF7L1 protein, human ; Transcription Factor 7-Like 1 Protein ; Cyclin D1 (136601-57-5) ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM2A protein, human (EC 1.14.11.27) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2020-10-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0236612
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  4. Article ; Online: Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome.

    Raška, Ivan

    Interdisciplinary toxicology

    2010  Volume 3, Issue 3, Page(s) 89–93

    Abstract: Ranged among laminopathies, Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall ... ...

    Abstract Ranged among laminopathies, Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned.
    Language English
    Publishing date 2010-03-29
    Publishing country Slovakia
    Document type Journal Article
    ZDB-ID 2503775-4
    ISSN 1337-9569 ; 1337-6853
    ISSN (online) 1337-9569
    ISSN 1337-6853
    DOI 10.2478/v10102-010-0018-y
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  5. Article ; Online: Hypocalcaemic cardiomyopathy: a description of two cases and a literature review.

    Válek, Martin / Roblová, Lenka / Raška, Ivan / Schaffelhoferová, Dita / Paleček, Tomáš

    ESC heart failure

    2020  Volume 7, Issue 3, Page(s) 1291–1301

    Abstract: Hypocalcaemic cardiomyopathy is a rare form of dilated cardiomyopathy. The authors here present two cases in which symptomatic dilated cardiomyopathy was the result of severe hypocalcaemia. First, we report about a 26-year-old woman with primary ... ...

    Abstract Hypocalcaemic cardiomyopathy is a rare form of dilated cardiomyopathy. The authors here present two cases in which symptomatic dilated cardiomyopathy was the result of severe hypocalcaemia. First, we report about a 26-year-old woman with primary hypoparathyroidism and then about a 74-year-old man with secondary hypoparathyroidism following a thyroidectomy. In both cases, the left ventricular systolic function improved after calcium supplementation. In the first case, a lack of compliance led to a repeated decrease of both serum calcium level and left ventricular systolic function. The authors also present a comprehensive summary of all cases of hypocalcaemic dilated cardiomyopathy that have been described in literature to date. The mean age of the affected patients was 48.3 years, of which 62% were female patients. The most common causes of hypocalcaemic cardiomyopathy are primary hypoparathyroidism (50%) and post-thyroidectomy hypoparathyroidism (26%). In the post-thyroidectomy subgroup, the median time for the development of hypocalcaemic cardiomyopathy is 10 years (range: 1.5 months to 36 years). Hypocalcaemic cardiomyopathy leads to heart failure with reduced ejection fraction in 87% of patients. Generally, the most common complications of hypoparathyroidism and/or hypocalcaemia are cerebral calcifications, cognitive deficit, and cataracts. Once calcium supplementation is administered, the disease has a good prognosis and, in most individuals, a significant improvement (21%) or even normalization (74%) of the left ventricular systolic function occurs.
    MeSH term(s) Adult ; Aged ; Calcium ; Cardiomyopathy, Dilated/diagnosis ; Cardiomyopathy, Dilated/etiology ; Female ; Humans ; Hypocalcemia/diagnosis ; Hypocalcemia/etiology ; Hypoparathyroidism/complications ; Hypoparathyroidism/diagnosis ; Male ; Middle Aged ; Thyroidectomy
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-04-03
    Publishing country England
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2814355-3
    ISSN 2055-5822 ; 2055-5822
    ISSN (online) 2055-5822
    ISSN 2055-5822
    DOI 10.1002/ehf2.12693
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  6. Article ; Online: The SC-35 Splicing Factor Interacts with RNA Pol II and A-Type Lamin Depletion Weakens This Interaction.

    Legartová, Soňa / Fagherazzi, Paolo / Stixová, Lenka / Kovařík, Aleš / Raška, Ivan / Bártová, Eva

    Cells

    2021  Volume 10, Issue 2

    Abstract: The essential components of splicing are the splicing factors accumulated in nuclear speckles; thus, we studied how DNA damaging agents and A-type lamin depletion affect the properties of these regions, positive on the SC-35 protein. We observed that ... ...

    Abstract The essential components of splicing are the splicing factors accumulated in nuclear speckles; thus, we studied how DNA damaging agents and A-type lamin depletion affect the properties of these regions, positive on the SC-35 protein. We observed that inhibitor of PARP (
    MeSH term(s) Cell Line, Tumor ; HeLa Cells ; Humans ; Lamins/metabolism ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; RNA Polymerase II/metabolism ; RNA Splicing Factors/metabolism
    Chemical Substances Lamins ; Poly(ADP-ribose) Polymerase Inhibitors ; RNA Splicing Factors ; PARP1 protein, human (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30) ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2021-02-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10020297
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  7. Article ; Online: Alternative isoforms of KDM2A and KDM2B lysine demethylases negatively regulate canonical Wnt signaling.

    Dijana Lađinović / Daniel Pinkas / Tijana Šopin / Otakar Raška / František Liška / Ivan Raška / Tomáš Vacík

    PLoS ONE, Vol 15, Iss 10, p e

    2020  Volume 0236612

    Abstract: A precisely balanced activity of canonical Wnt signaling is essential for a number of biological processes and its perturbation leads to developmental defects or diseases. Here, we demonstrate that alternative isoforms of the KDM2A and KDM2B lysine ... ...

    Abstract A precisely balanced activity of canonical Wnt signaling is essential for a number of biological processes and its perturbation leads to developmental defects or diseases. Here, we demonstrate that alternative isoforms of the KDM2A and KDM2B lysine demethylases have the ability to negatively regulate canonical Wnt signaling. These KDM2A and KDM2B isoforms (KDM2A-SF and KDM2B-SF) lack the N-terminal demethylase domain, but they still have the ability to bind to CpG islands in promoters and to interact with their protein partners via their other functional domains. We have observed that KDM2A-SF and KDM2B-SF bind to the promoters of axin 2 and cyclin D1, two canonical Wnt signaling target genes, and repress their activity. Moreover, KDM2A-SF and KDM2B-SF are both able to strongly repress a Wnt-responsive luciferase reporter. The transcriptional repression mediated by KDM2A-SF and KDM2B-SF, but also by KDM2A-LF, is dependent on their DNA binding domain, while the N-terminal demethylase domain is dispensable for this process. Surprisingly, KDM2B-LF is unable to repress both the endogenous promoters and the luciferase reporter. Finally, we show that both KDM2A-SF and KDM2B-SF are able to interact with TCF7L1, one of the transcriptional mediators of canonical Wnt signaling. KDM2A-SF and KDM2B-SF are thus likely to negatively affect the transcription of canonical Wnt signaling target genes by binding to their promoters and by interacting with TCF7L1 and other co-repressors.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570 ; 572
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  8. Article ; Online: KDM2A/B lysine demethylases and their alternative isoforms in development and disease.

    Vacík, Tomáš / Lađinović, Dijana / Raška, Ivan

    Nucleus (Austin, Tex.)

    2018  Volume 9, Issue 1, Page(s) 431–441

    Abstract: Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular ...

    Abstract Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular mechanisms of their action are now fairly well understood. However, little attention has been paid to naturally occurring alternative isoforms of chromatin modifying proteins and to their biological roles. In this review, we focus on mammalian KDM2A and KDM2B, the only two lysine demethylases whose genes have been described to produce also an alternative isoform lacking the N-terminal demethylase domain. These short KDM2A/B-SF isoforms arise through alternative promoter usage and seem to play important roles in development and disease. We hypothesise about the biological significance of these alternative isoforms, which might represent a more common evolutionarily conserved regulatory mechanism.
    MeSH term(s) Animals ; Humans ; Isoenzymes/deficiency ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Jumonji Domain-Containing Histone Demethylases/deficiency ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Neoplasms/enzymology ; Neoplasms/metabolism
    Chemical Substances Isoenzymes ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-)
    Language English
    Publishing date 2018-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2619626-8
    ISSN 1949-1042 ; 1949-1034
    ISSN (online) 1949-1042
    ISSN 1949-1034
    DOI 10.1080/19491034.2018.1498707
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  9. Article ; Online: Vibrio vulnificus

    Lipový, Bretislav / Mager, Radomir / Raška, Filip / Hanslianová, Marketa / Blažek, Josef / Křemečková, Hana / Suchánek, Ivan / Hladík, Martin

    The international journal of lower extremity wounds

    2021  Volume 22, Issue 1, Page(s) 200–207

    Abstract: Necrotizing fasciitis is a life-threatening skin and soft tissue infection associated with high morbidity and mortality in adult patients. This infection can present as either type 1 infection caused by a mixed microflora ( ...

    Abstract Necrotizing fasciitis is a life-threatening skin and soft tissue infection associated with high morbidity and mortality in adult patients. This infection can present as either type 1 infection caused by a mixed microflora (
    MeSH term(s) Adult ; Humans ; Fasciitis, Necrotizing/diagnosis ; Vibrio vulnificus ; Soft Tissue Infections/diagnosis ; Soft Tissue Infections/complications ; Acinetobacter baumannii ; Vibrio Infections/complications
    Language English
    Publishing date 2021-04-15
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2171119-7
    ISSN 1552-6941 ; 1534-7346
    ISSN (online) 1552-6941
    ISSN 1534-7346
    DOI 10.1177/15347346211004305
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  10. Article ; Online: Expression of Concern: CENP-C binds the alpha-satellite DNA in vivo at specific centromere domains.

    Politi, Valeria / Perini, Giovanni / Trazzi, Stefania / Pliss, Artem / Raska, Ivan / Earnshaw, William C / Valle, Giuliano Della

    Journal of cell science

    2022  Volume 135, Issue 18

    Language English
    Publishing date 2022-09-26
    Publishing country England
    Document type Journal Article ; Expression of Concern
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.260575
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