PURPOSE: This study aimed to evaluate one-year clinical outcomes in cataract patients with pre-existing corneal astigmatism implanted with a biconvex aspheric toric monofocal intraocular lens (IOL) with a double C-loop haptic-design. METHODS: One hundred and eighteen patients (236 eyes) with corneal astigmatism (≥0.75D) were implanted bilaterally with the PODEYE toric IOL and assessed up to 1-year after surgery. Postoperative evaluation included monocular and binocular uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), under both photopic and mesopic lighting conditions, refraction, photopic and mesopic contrast sensitivity (with and without glare), and rotational stability. RESULTS: At the last postoperative visit, 74.6% and 95.8% of eyes were within ±0.50D and ±1.00D of the target refraction, respectively. About 78.0% and 97.5% of eyes showed a postoperative refractive cylinder of ≤0.50D and ≤1.00D, respectively. The mean manifest spherical equivalent value was 0.16±0.40D, and the mean refractive cylinder value was -0.42±0.33D. 97.5% and 100% of patients had a binocular UDVA and CDVA of ≥20/32, respectively. The mean binocular UDVA and CDVA were 0.01±0.09 and -0.03±0.07 logMAR, respectively. Under mesopic conditions, 79.5% and 89.8% of patients showed a binocular UDVA and CDVA of ≥20/32, respectively. The mean binocular UDVA and CDVA were 0.15±0.11 and 0.10±0.10 logMAR, respectively. Binocular contrast sensitivity function both under photopic and mesopic conditions was good. The mean absolute IOL rotation was 2.52±2.59 degrees with 98.56% of eyes having a rotation of less than 10 degrees. CONCLUSION: Bilateral implantation of an aspheric toric monofocal IOL with a double C-loop haptic design in cataract patients with corneal astigmatism provides good visual and refractive outcomes up to 1-year post-surgery.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• klinické zkoušky MeSH

PURPOSE: To show the visual and refractive outcomes in cataract patients with corneal astigmatism when bilaterally implanted with a biconvex aspheric toric monofocal intraocular lens (IOL) with a double C-loop haptic-design. METHODS: Forty-seven cataract patients (94 eyes) with corneal astigmatism (≥0.75D) were implanted with the monofocal PODEYE toric IOL and assessed for 4-6 months post-surgery. Measurements included monocular and binocular uncorrected-distance visual acuity (UDVA) and corrected-distance visual acuity (CDVA), under both photopic and mesopic lighting conditions. Refraction, photopic and mesopic contrast sensitivity (with and without glare), and rotational stability were also recorded at the last postoperative visit. RESULTS: At 4-6 months, 78.2% and 98.9% of eyes were within ±0.50D and ±1.00D of the target refraction, respectively. The mean spherical equivalent and refractive cylinder values were 0.09±0.35D and -0.36±0.35D, respectively. 76.5% and 98.8% of eyes presented a postoperative refractive cylinder of ≤0.50D and ≤1.00D, respectively. 91.5% and 100% of patients had a binocular UDVA and CDVA of ≥20/25, respectively. The mean binocular UDVA and CDVA were 0.02±0.08 and -0.02±0.07 logMAR, respectively. Under mesopic conditions, 78.7% and 83.0% of patients presented a binocular UDVA and CDVA ≥20/32, respectively. The mean binocular UDVA and CDVA were 0.15±0.11 and 0.12±0.11 logMAR, respectively. The patients showed good contrast sensitivity under photopic and mesopic conditions. The mean absolute IOL rotation was 1.22±2.21 degrees with 97.87% of eyes having a rotation of <10 degrees. CONCLUSION: This study shows good visual and refractive outcomes for the PODEYE toric IOL when implanted bilaterally in cataract patients with corneal astigmatism.

• Publikační typ
• kazuistiky MeSH
• klinické zkoušky MeSH

Double-strand breaks (DSBs) are the most severe type of DNA damage. Previously, we demonstrated that RNA polymerase II (RNAPII) phosphorylated at the tyrosine 1 (Y1P) residue of its C-terminal domain (CTD) generates RNAs at DSBs. However, the regulation of transcription at DSBs remains enigmatic. Here, we show that the damage-activated tyrosine kinase c-Abl phosphorylates hSSB1, enabling its interaction with Y1P RNAPII at DSBs. Furthermore, the trimeric SOSS1 complex, consisting of hSSB1, INTS3, and c9orf80, binds to Y1P RNAPII in response to DNA damage in an R-loop-dependent manner. Specifically, hSSB1, as a part of the trimeric SOSS1 complex, exhibits a strong affinity for R-loops, even in the presence of replication protein A (RPA). Our in vitro and in vivo data reveal that the SOSS1 complex and RNAPII form dynamic liquid-like repair compartments at DSBs. Depletion of the SOSS1 complex impairs DNA repair, underscoring its biological role in the R-loop-dependent DNA damage response.

• MeSH
• DNA vazebné proteiny * metabolismus   MeSH
• oprava DNA MeSH
• poškození DNA MeSH
• RNA-polymerasa II * metabolismus   MeSH
• separace fází MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

p53 is one of the most important tumor suppressors which responds to DNA damage by binding to DNA and regulating the transcription of genes involved in cell cycle arrest, apoptosis, or senescence. As it was shown previously, p53 binding to DNA is strongly influenced by DNA topology. DNA supercoiling is fundamentally important for a wide range of biological processes including DNA transcription, replication, recombination, control of gene expression and genome organization. In this study, we investigated the cruciform structures formation of various inverted repeats in p53-responsive sequences from p21, RGC, mdm2 and GADD45 promoters under negative superhelical stress, and analyzed the effects of these DNA topology changes on p53-DNA binding. We demonstrated using three different methods (gel retardation analyses, ELISA and magnetic immunoprecipitation assay) that the p53 protein binds preferentially to negatively supercoiled plasmid DNAs with p53-responsive sequence presented as a cruciform structure. Not only the appearance of the cruciform structures within naked supercoiled DNA, but also the potential of the binding sites for adopting the non-B structures can contribute to a more favorable p53-DNA complex. Copyright 2009 Elsevier Inc. All rights reserved.

• MeSH
• buněčné linie MeSH
• ELISA MeSH
• inhibitor p21 cyklin-dependentní kinasy genetika   MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• jednovláknová DNA chemie   metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• obrácené repetice MeSH
• plazmidy chemie   metabolismus   MeSH
• protoonkogenní proteiny c-mdm2 genetika   MeSH
• regulace genové exprese MeSH
• retardační test MeSH
• sekvence nukleotidů MeSH
• superhelikální DNA chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Non-enveloped icosahedral double-stranded RNA (dsRNA) viruses possess multifunctional capsids required for their proliferation. Whereas protozoan/fungal dsRNA viruses have a relatively simple capsid structure, which suffices for the intracellular phase in their life cycle, metazoan dsRNA viruses have acquired additional structural features as an adaptation for extracellular cell-to-cell transmission in multicellular hosts. Here, we present the first atomic model of a metazoan dsRNA totivirus-like virus and the structure reveals three unique structural traits: a C-terminal interlocking arm, surface projecting loops, and an obstruction at the pore on the 5-fold symmetry axis. These traits are keys to understanding the capsid functions of metazoan dsRNA viruses, such as particle stability and formation, cell entry, and endogenous intraparticle transcription of mRNA. On the basis of molecular dynamics simulations of the obstructed pore, we propose a possible mechanism of intraparticle transcription in totivirus-like viruses, which dynamically switches between open and closed states of the pore(s).

• MeSH
• dvouvláknová RNA chemie   genetika   MeSH
• elektronová kryomikroskopie MeSH
• internalizace viru MeSH
• kapsida chemie   metabolismus   MeSH
• replikace viru MeSH
• RNA virová chemie   genetika   MeSH
• simulace molekulární dynamiky MeSH
• Totivirus chemie   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• cirkulární dichroismus MeSH
• DNA chemie   metabolismus   MeSH
• elektronová mikroskopie MeSH
• konformace nukleové kyseliny MeSH
• peptidové fragmenty chemie   metabolismus   MeSH
• proteiny s vysokou pohyblivostí chemie   metabolismus   MeSH
• skot MeSH
• superhelikální DNA metabolismus   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH

G-quadruplexes are unusual DNA and RNA secondary structures ubiquitous in a variety of organisms including vertebrates, plants, viruses and bacteria. The folding topology and stability of intramolecular G-quadruplexes are determined to a large extent by their loops. Loop permutation is defined as swapping two or three of these regions so that intramolecular G-quadruplexes only differ in the sequential order of their loops. Over the past two decades, both length and base composition of loops have been studied extensively, but a systematic study on the effect of loop permutation has been missing. In the present work, 99 sequences from 21 groups with different loop permutations were tested. To our surprise, both conformation and thermal stability are greatly dependent on loop permutation. Loop permutation actually matters as much as loop length and base composition on G-quadruplex folding, with effects on Tm as high as 17°C. Sequences containing a longer central loop have a high propensity to adopt a stable non-parallel topology. Conversely, sequences containing a short central loop tend to form a parallel topology of lower stability. In addition, over half of interrogated sequences were found in the genomes of diverse organisms, implicating their potential regulatory roles in the genome or as therapeutic targets. This study illustrates the structural roles of loops in G-quadruplex folding and should help to establish rules to predict the folding pattern and stability of G-quadruplexes.

• MeSH
• algoritmy MeSH
• cirkulární dichroismus MeSH
• DNA chemie   MeSH
• G-kvadruplexy * MeSH
• konformace nukleové kyseliny * MeSH
• sekvence nukleotidů MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Regulated protein synthesis via changes in mRNA structures forms an important part of how prokaryotic cells adapt protein expression in response to changes in the environment. Little is known regarding how this concept has adapted to regulate mRNA translation via signaling pathways in mammalian cells. Here, we show that following phosphorylation by the ataxia telangiectasia mutated (ATM) kinase at serine 403, the C-terminal RING domain of HDMX binds the nascent p53 mRNA to promote a conformation that supports the p53 mRNA-HDM2 interaction and the induction of p53 synthesis. HDMX and its homolog HDM2 bind the same p53 internal ribosome entry sequences (IRES) structure but with different specificity and function. The results show how HDMX and HDM2 act as nonredundant IRES trans-acting factors (ITAFs) to bring a positive synergistic effect on p53 expression during genotoxic stress by first altering the structure of the newly synthesized p53 mRNA followed by stimulation of translation.

• MeSH
• ATM protein metabolismus   MeSH
• fosforylace MeSH
• jaderné proteiny chemie   fyziologie   MeSH
• lidé MeSH
• messenger RNA chemie   genetika   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• obrácené repetice MeSH
• poškození DNA MeSH
• posttranskripční úpravy RNA MeSH
• posttranslační úpravy proteinů MeSH
• proteosyntéza MeSH
• protoonkogenní proteiny c-mdm2 metabolismus   MeSH
• protoonkogenní proteiny chemie   fyziologie   MeSH
• regulace genové exprese MeSH
• sbalování RNA MeSH
• sekvence nukleotidů MeSH
• Sf9 buňky MeSH
• Spodoptera MeSH
• substrátová specifita MeSH
• terciární struktura proteinů MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• DNA MeSH
• genetika MeSH
• geny MeSH
• molekulární biologie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• biologie

Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed "alternative lengthening of telomeres" (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutSβ, a heterodimer of MSH2 and MSH3 subunits, is enriched at telomeres in ALT cancer cells, where it prevents the accumulation of telomeric G-quadruplex (G4) structures and R-loops. Cells depleted of MSH3 display increased incidence of R-loop-dependent telomere fragility and accumulation of telomeric C-circles. We also demonstrate that purified MutSβ recognizes and destabilizes G4 structures in vitro. These data suggest that MutSβ destabilizes G4 structures in ALT telomeres to regulate TERRA R-loops, which is a prerequisite for maintenance of telomere integrity during ALT.

• MeSH
• DNA metabolismus   MeSH
• homeostáza telomer MeSH
• lidé MeSH
• nádory * genetika   MeSH
• R-smyčka MeSH
• RNA dlouhá nekódující * metabolismus   MeSH
• telomery metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH