As predictive motor control is an important index of neuromotor development and maturation, we developed two touchscreen tablet-based tests of this function. Our aim was to investigate the reliability and validity of both a rapid manual interception test and a pursuit tracking test, using a sample of 124 children (62 boys and 62 girls) from two age groups (7-8-year-oldss and 9-10-year-olds). Participants performed both tablet tests with a stylus (sample rate 100 Hz) with both a visible and a temporarily invisible moving target. Confirmatory factor analyses and omega coefficients showed that both tests were univariate methods that provided a reliable assessment of the latent factor related to predictive visuomotor control. As would be expected, compared to younger children, older children performed better on both manual interception and pursuit tracking. The correlations between the latent factors of the two tests at 95% confidence intervals (-.276, -.608) suggested shared variance. Thus, the touchscreen-tablet based tests of rapid manual interception and manual pursuit tracking appear psychometrically suitable for assessing the neuromotor ability of predictive control in 7-10-year-old children.

• MeSH
• dítě MeSH
• faktorová analýza statistická MeSH
• lidé MeSH
• mladiství MeSH
• reprodukovatelnost výsledků * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The authors wish to make the following corrections to this paper [...].

• Publikační typ
• tisková chyba MeSH

Approximately one third of children with steroid-resistant nephrotic syndrome (SRNS) carry pathogenic variants in one of the many associated genes. The WT1 gene coding for the WT1 transcription factor is among the most frequently affected genes. Cases from the Czech national SRNS database were sequenced for exons 8 and 9 of the WT1 gene. Eight distinct exonic WT1 variants in nine children were found. Three children presented with isolated SRNS, while the other six manifested with additional features. To analyze the impact of WT1 genetic variants, wild type and mutant WT1 proteins were prepared and the DNA-binding affinity of these proteins to the target EGR1 sequence was measured by microscale thermophoresis. Three WT1 mutants showed significantly decreased DNA-binding affinity (p.Arg439Pro, p.His450Arg and p.Arg463Ter), another three mutants showed significantly increased binding affinity (p.Gln447Pro, p.Asp469Asn and p.His474Arg), and the two remaining mutants (p.Cys433Tyr and p.Arg467Trp) showed no change of DNA-binding affinity. The protein products of WT1 pathogenic variants had variable DNA-binding affinity, and no clear correlation with the clinical symptoms of the patients. Further research is needed to clarify the mechanisms of action of the distinct WT1 mutants; this could potentially lead to individualized treatment of a so far unfavourable disease.

• MeSH
• dítě MeSH
• DNA terapeutické užití   MeSH
• léková rezistence MeSH
• lidé MeSH
• mutace MeSH
• nefrotický syndrom * farmakoterapie   genetika   metabolismus   MeSH
• proteiny WT1 * genetika   metabolismus   MeSH
• steroidy farmakologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The emergence of antibiotic resistance in opportunistic pathogens represents a huge problem, the solution for which may be a treatment with a combination of multiple antimicrobial agents. Sodium salt of cobalt bis-dicarbollide (COSAN.Na) is one of the very stable, low-toxic, amphiphilic boron-rich sandwich complex heteroboranes. This compound has a wide range of potential applications in the biological sciences due to its antitumor, anti-HIV-1, antimicrobial and antibiofilm activity. Our study confirmed the ability of COSAN.Na (in the concentration range 0.2-2.48 μg/mL) to enhance tetracycline, erythromycin, and vancomycin action towards Staphylococcus epidermidis planktonic growth with an additive or synergistic effect (e.g., the combination of 1.24 μg/mL COSAN.Na and 6.5 μg/mL TET). The effective inhibitory concentration of antibiotics was reduced up to tenfold most efficiently in the case of tetracycline (from 65 to 6.5 μg/mL). In addition, strong effect of COSAN.Na on disruption of the cell envelopes was determined using propidium iodide uptake measurement and further confirmed by transmission electron microscopy. The combination of amphiphilic COSAN.Na with antibiotics can therefore be considered a promising way to overcome antibiotic resistance in Gram-positive cocci.

• Publikační typ
• časopisecké články MeSH

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives' action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C70 derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C70 derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription-without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives' oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.

• MeSH
• fullereny metabolismus   farmakologie   MeSH
• genom virový účinky léků   MeSH
• genové produkty gag - virus lidské imunodeficience metabolismus   MeSH
• HEK293 buňky MeSH
• HIV-1 účinky léků   genetika   metabolismus   fyziologie   MeSH
• látky proti HIV metabolismus   farmakologie   MeSH
• lidé MeSH
• nukleokapsida - proteiny metabolismus   MeSH
• reverzní transkripce MeSH
• RNA virová metabolismus   MeSH
• svlékání virového obalu účinky léků   MeSH
• vazba proteinů MeSH
• virion metabolismus   MeSH
• zabalení virového genomu účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles' heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.

• MeSH
• acidóza patofyziologie   MeSH
• antitumorózní látky farmakologie   MeSH
• citrátový cyklus účinky léků   MeSH
• energetický metabolismus MeSH
• fyziologická adaptace MeSH
• glukosa metabolismus   MeSH
• glykolýza MeSH
• kapryláty farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina mléčná metabolismus   MeSH
• lidé MeSH
• mitochondrie účinky léků   metabolismus   patologie   MeSH
• nádorové buňky kultivované MeSH
• nádorové mikroprostředí * MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• oxidační stres MeSH
• sulfidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• směrnice MeSH

Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC50 > 50 μM, amine 3 IC50 0.21 and amine 14 IC50 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only 4 and 6 were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that 8, 10, 16, 17 and 18 have had IC50i > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds 4 and 12. In the cases of 2, 8, 9, 10, 16, 17 and 18, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat.

• Publikační typ
• časopisecké články MeSH

Vysokoškolský učební text, který se zaměřuje na závislosti, jejich diagnostiku a léčbu.

• MeSH
• diferenciální diagnóza MeSH
• duševně nemocní psychologie   MeSH
• duševní poruchy MeSH
• návykové chování MeSH
• psychiatrická rehabilitace MeSH
• psychologické techniky MeSH
• psychoterapie MeSH
• uživatelé drog psychologie   MeSH

• Konspekt
• Psychopatologie
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• psychologie, klinická psychologie
• psychiatrie
• adiktologie
• NLK Publikační typ
• učebnice vysokých škol

• Publikační typ
• abstrakt z konference MeSH