• Klíčová slova
• V-aktinin, genové varianty, polymorfismus R577X,
• MeSH
• aktinin genetika   MeSH
• alely MeSH
• běh MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kosterní svaly MeSH
• lehká atletika MeSH
• lidé MeSH
• tělesná výkonnost MeSH
• Check Tag
• lidé MeSH

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the aim of this study was twofold: (1) to determine the association of ACTN3 rs1815739 polymorphism with changes in physical performance in response to six weeks of training in elite basketball players using 30 m sprint and Yo-Yo Intermittent Recovery Test Level 2 (IR 2) tests, and (2) to compare ACTN3 genotype and allelic frequencies between elite basketball players and controls. The study included a total of 363 individuals, comprising 101 elite basketball players and 262 sedentary individuals. Genomic DNA was isolated from oral epithelial cells or leukocytes, and genotyping was performed by real-time PCR using KASP genotyping method or by microarray analysis. We found that the frequency of the ACTN3 rs1815739 XX genotype was significantly lower in basketball players compared to controls (10.9 vs. 21.4%, p = 0.023), suggesting that RR/RX genotypes were more favorable for playing basketball. Statistically significant (p = 0.045) changes were observed in Yo-Yo IRT 2 performance measurement tests in basketball players with the RR genotype only. In conclusion, our findings suggest that the carriage of the ACTN3 rs1815739 R allele may confer an advantage in basketball.

• MeSH
• aktinin * genetika   MeSH
• basketbal * MeSH
• frekvence genu MeSH
• genotyp MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

24letá žena měla na ventromediální straně levého stehna oválné ložisko tužší konzistence barvykůže, s nahnědlým lemem. Léze byla subjektivně asymptomatická a zvolna 1,5 roku progredovala.Bioptické vyšetření prokázalo dermatomyofibrom. Naše práce shrnuje morfologické a biologickévlastnosti afekce a dále klinickou a histopatologickou diferenciální diagnózu.

A 24-year old female had an oval indurated plaque skin colour with a brownish peripheral borderon the ventro-medial aspect of the left thigh. The lesion was asymptomatic subjectively and slowlyprogressed over 1.5 years. Biopsy demonstrated a dermatomyofibroma. The report summarizes themorphological and biological characteristics of the affection as well as the clinical and histopathologicaldifferential diagnosis of it.

• MeSH
• aktinin MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• lidé MeSH
• myofibromatóza diagnóza   chirurgie   patologie   MeSH
• nádory kůže diagnóza   chirurgie   patologie   MeSH
• vimentin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

Pathogenic variants in ACTN2, coding for alpha-actinin 2, are known to be rare causes of Hypertrophic Cardiomyopathy. However, little is known about the underlying disease mechanisms. Adult heterozygous mice carrying the Actn2 p.Met228Thr variant were phenotyped by echocardiography. For homozygous mice, viable E15.5 embryonic hearts were analysed by High Resolution Episcopic Microscopy and wholemount staining, complemented by unbiased proteomics, qPCR and Western blotting. Heterozygous Actn2 p.Met228Thr mice have no overt phenotype. Only mature males show molecular parameters indicative of cardiomyopathy. By contrast, the variant is embryonically lethal in the homozygous setting and E15.5 hearts show multiple morphological abnormalities. Molecular analyses, including unbiased proteomics, identified quantitative abnormalities in sarcomeric parameters, cell-cycle defects and mitochondrial dysfunction. The mutant alpha-actinin protein is found to be destabilised, associated with increased activity of the ubiquitin-proteasomal system. This missense variant in alpha-actinin renders the protein less stable. In response, the ubiquitin-proteasomal system is activated; a mechanism that has been implicated in cardiomyopathies previously. In parallel, a lack of functional alpha-actinin is thought to cause energetic defects through mitochondrial dysfunction. This seems, together with cell-cycle defects, the likely cause of the death of the embryos. The defects also have wide-ranging morphological consequences.

• MeSH
• aktinin metabolismus   MeSH
• hypertrofická kardiomyopatie * MeSH
• kardiomyopatie * MeSH
• myši MeSH
• srdce MeSH
• ubikvitiny MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nuclear actin plays an important role in such processes as chromatin remodeling, transcriptional regulation, RNA processing, and nuclear export. Recent research has demonstrated that actin in the nucleus probably exists in dynamic equilibrium between monomeric and polymeric forms, and some of the actin-binding proteins, known to regulate actin dynamics in cytoplasm, have been also shown to be present in the nucleus. In this paper, we present ultrastructural data on distribution of actin and various actin-binding proteins (alpha-actinin, filamin, p190RhoGAP, paxillin, spectrin, and tropomyosin) in nuclei of HeLa cells and resting human lymphocytes. Probing extracts of HeLa cells for the presence of actin-binding proteins also confirmed their presence in nuclei. We report for the first time the presence of tropomyosin and p190RhoGAP in the cell nucleus, and the spatial colocalization of actin with spectrin, paxillin, and alpha-actinin in the nucleolus.

• MeSH
• aktinin MeSH
• aktiny analýza   MeSH
• buněčné jádro chemie   ultrastruktura   MeSH
• financování organizované MeSH
• HeLa buňky MeSH
• jaderné proteiny analýza   MeSH
• lidé MeSH
• lymfocyty chemie   ultrastruktura   MeSH
• mikrofilamentové proteiny analýza   MeSH
• paxilin MeSH
• proteiny aktivující GTPasu MeSH
• spektrin MeSH
• tropomyosin MeSH
• Check Tag
• lidé MeSH

The differentiation of pluripotent embryonic stem (ES) cells into various lineages in vitro represents an important tool for studying the mechanisms underlying mammalian embryogenesis. It is a key technique in studies evaluating the molecular mechanisms of cardiomyogenesis and heart development and also in embryotoxicology. Herein, modest modifications of the basic protocol for ES cell differentiation into cardiomyocytes were evaluated in order to increase the yield and differentiation status of developed cardiomyocytes. Primarily, the data show that ES cell cultivation in the form of non-adherent embryoid bodies (EBs) for 5 days compared to 8 days significantly improved cardiomyogenic differentiation. This is illustrated by the appearance of beating foci in the adherent EBs layer at earlier phases of differentiation from day 10 up to day 16 and by the significantly higher expression of genes characteristic of cardiomyogenic differentiation (sarcomeric alpha actinin, myosin heavy chain alpha and beta, myosin light chain 2 and 7, and transcriptional factor Nkx2.5) in EBs cultivated under non-adherent conditions for 5 days. The ratio of cardiomyocytes per other cells was also potentiated in EBs cultivated in non-adherent conditions for only 5 days followed by cultivation in adherent serum-free culture conditions. Nevertheless, the alteration in the percentage of beating foci among these two tested cultivation conditions vanished at later phases and also did not affect the total number of cardiomyocytes determined as myosin heavy chain positive cells at the end of the differentiation process on day 20. Thus, although these modifications of the conditions of ES cells differentiation may intensify cardiomyocyte differentiation, the final count of cardiomyocytes might not change. Thus, serum depletion was identified as a key factor that intensified cardiomyogenesis. Further, the treatment of EBs with N-acetylcysteine, a reactive oxygen species scavenger, did not affect the observed increase in cardiomyogenesis under serum depleted conditions. Interestingly, a mild induction of the ventricular-like phenotype of cardiomyocytes was observed in 5-day-old EBs compared to 8-day-old EBs. Overall, these findings bring crucial information on the mechanisms of ES cells differentiation into cardiomyocytes and on the establishment of efficient protocols for the cardiomyogenic differentiation of ES cells. Further, the importance of determining the absolute number of formed cardiomyocyte-like cells per seeded pluripotent cells in contrast to the simple quantification of the ratios of cells is highlighted.

• MeSH
• acetylcystein aplikace a dávkování   MeSH
• aktinin genetika   MeSH
• embryonální kmenové buňky cytologie   MeSH
• homeoboxový protein Nkx-2.5 genetika   MeSH
• kardiomyocyty cytologie   MeSH
• kultivační média bez séra * MeSH
• kultivované buňky MeSH
• myosiny genetika   MeSH
• myši MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In polarized motile cells, stress fibers display specific three-dimensional organization. Ventral stress fibers, attached to focal adhesions at both ends, are restricted to the basal side of the cell and nonprotruding cell sides. Dorsal fibers, transverse actin arcs, and perinuclear actin fibers emanate from protruding cell front toward the nucleus and toward apical side of the cell. Perinuclear cap fibers further extend above the nucleus, associate with nuclear envelope through LINC (linker of nucleoskeleton and cytoskeleton) complex and terminate in focal adhesions at cell rear. How are perinuclear actin fibers formed is poorly understood. We show that the formation of perinuclear actin fibers requires dorsal stress fibers that polymerize from focal adhesions at leading edge, and transverse actin arcs that are interconnected with dorsal fibers in spots rich in α-actinin-1. During cell polarization, the interconnected dorsal fibers and transverse arcs move from leading edge toward dorsal side of the cell. As they move, transverse arcs associate with one end of stress fibers present at nonprotruding cell sides, move them above the nucleus thus forming perinuclear actin fibers. Furthermore, the formation of perinuclear actin fibers induces temporal rotational movement of the nucleus resulting in nuclear reorientation to the direction of migration. These results suggest that the network of dorsal fibers, transverse arcs, and perinuclear fibers transfers mechanical signal between the focal adhesions and nuclear envelope that regulates the nuclear reorientation in polarizing cells.

• MeSH
• aktinin fyziologie   MeSH
• aktiny fyziologie   MeSH
• buněčné jádro fyziologie   MeSH
• buněčné linie MeSH
• buněčný převod mechanických signálů fyziologie   MeSH
• fibroblasty fyziologie   MeSH
• fokální adheze fyziologie   MeSH
• kontraktilní svazky fyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• pohyb buněk fyziologie   MeSH
• pohyb fyziologie   MeSH
• polarita buněk fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodníky MeSH

Fyzická kondice každého jedince je primárně limitována jeho genotypem. V současné době je popsáno více než 150 genů (většinou se jedná o autozomální geny, ale i geny na Y chromozomech a geny mitochondriální DNA), které zásadně ovlivňují fyzickou zdatnost, svalovou výkonnost a vytrvalost organizmu. V budoucnosti bude určitě hrát personální genomika sportu důležitou roli při rozhodování o správné sportovní aktivitě, metodice tréninku, výživě a používání léků. Některé geny ovlivňující zejména výkonnost jsme schopni již rutinně vyšetřovat v naší republice.

Physical condition of each individual is primarily determined by his genotype. More than 150 genes are currently described that fundamentally affect physical fitness, muscle strength and endurance of the body (mostly autosomal genes, but also on the Y chromosome and mitochondrial DNA genes). Personal genomics of sport will in the future definitely play an important role in choosing the right sport activity, methodology, training, nutrition and drug use. Some of the genes, particularly those affecting efficiency can be routinely investigated in our country.

• Klíčová slova
• svalová aktivita, svalový výkon, genový doping, genetický doping,
• MeSH
• aktinin genetika   MeSH
• angiotensin konvertující enzym genetika   MeSH
• cvičení MeSH
• dědičnost MeSH
• doping ve sportu MeSH
• genotyp * MeSH
• kosterní svalová vlákna * fyziologie   MeSH
• kosterní svaly fyziologie   fyziologie   metabolismus   MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• proteinkinasy aktivované AMP genetika   MeSH
• sporty MeSH
• svalová síla genetika   MeSH
• tělesná výkonnost * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Nephrotic syndrome (NS) is a serious condition characterized by massive proteinuria which is most frequently caused by minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN) and IgA nephropathy (IGAN). In adult patients with MCD/FSGS the most frequent genetic abnormality observed was the mutation in one of the 3 following genes : NPHS1, ACTN4 and TRPC6. Determination of gene mutations can influence the management and treatment. Aim of the proposal is the mutational analysis of the above mentioned genes in the patients with histologically proven diagnosis of MCD/FSGS. These patients are frequently resistant to immunosupressive therapy but do not recur after renal transplantation. The following part of the grant project is the determination of the significance of the genetic polymorphisms in the three mentioned genes and in their promotors on the progression of selected glomerulonephritidis (MCD, FSGS, MGN, IGAN).

Anotace I: Nefrotický syndrom je závažný klinický stav vyznačující se především proteinurií, jehož podkladem jsou nejčastěji minimální změny glomerulů (MCN), fokální a segmentální glomeruloskleróza (FSGS), membranózní nefropatie (MGN) a IgA glomerulonefritida (IGAN). Anotace II: U dospělých nemocných s FSGS rezistentních na imunosupresi byly nejčastěji stanoveny mutace v následujících 3 genech: NPHS2, ACTN4 a TRPC6. Zjištění mutací může ovlivnit terapeutický postup. Anotace III: Cílem projektu je mutační analýza ve zmíněných genech u dospělých pacientů s histologicky ověřenou diagnózou FSGS/MCN. Tito pacienti jsou většinou resistentní k imunosupresivní terapii, ale po transplantaci ledviny NS nerelabuje. Anotace IV: Stanovení vlivu polymorfismů ve výšepopsaných genů a jejich promotorech umožní stanovení dalších prognostických faktorů vybraných glomerulonefritid (MCN, FSGS, MGN, IGAN).

• MeSH
• aktinin genetika   MeSH
• fokálně segmentální glomeruloskleróza MeSH
• IgA nefropatie MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• membranózní glomerulonefritida MeSH
• mutace MeSH
• nefrotický syndrom MeSH
• polymorfismus genetický MeSH
• proteinurie MeSH
• suprese genetická MeSH
• vápníkové kanály MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• nefrologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

α-Actinin 4, encoded by ACTN4, is an F-actin crosslinking protein which belongs to the spectrin gene superfamily. It has a head-to-tail homodimer structure with three main domains. Mutations in ACTN4 are associated with idiopathic nephrotic syndrome (NS). However, until today only a few mutations have been described in this gene. We used genomic DNA of 48 patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) to screen for ACTN4 mutations by high-resolution melting analysis (HRM). Suspect samples were sequenced and compared with healthy controls. To investigate the prevalence and possible effect of some substitutions found in FSGS/MCD patients we also looked for these changes in patients with IgA nephropathy (IgAN) and membranous glomerulonephritis (MGN). We found 20 exonic and intronic substitutions in the group of 48 Czech patients. The substitution 2242A>G (p.Asn748Asp) is a candidate mutation which was identified in one patient but not in any of the 200 healthy controls. Exon 19 seems to be a variable region due to the amount of revealed polymorphisms. In this region we also found three unreported substitutions in IgAN patients, c.2351C>T (p.Ala784Val), c.2378G>A (p.Cys793Tyr) and c.2393G>A (p.Gly798Asp). These substitutions were not found in any tested healthy controls. To conclude, the ACTN4 mutations are not a frequent cause of FSGS/MCD in Czech adult patients. One new ACTN4 mutation has been identified.

• MeSH
• aktinin genetika   MeSH
• bodová mutace MeSH
• denaturace nukleových kyselin MeSH
• dospělí MeSH
• exony genetika   MeSH
• fokálně segmentální glomeruloskleróza epidemiologie   genetika   MeSH
• IgA nefropatie epidemiologie   genetika   MeSH
• introny genetika   MeSH
• konsenzuální sekvence MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoidní nefróza epidemiologie   genetika   MeSH
• membranózní glomerulonefritida genetika   MeSH
• missense mutace MeSH
• molekulární sekvence - údaje MeSH
• mutační analýza DNA MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• substituce aminokyselin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH