triplex Dotaz Zobrazit nápovědu
Kontinuálny únik moču pri súčasne normálnej mikcii môže byť príznakom ektopického vyústenia močovodu u dievčat. Prezentujem kazuistiku 6 roč- ného dievčatka, ktoré trpelo nepretržitým denným aj nočným únikom moču. Diagnostika a terapia u die- ťaťa bola uskutočnená na Klinike pediatrickej urológie. V diagnostike sme použili sonografiu, vylučovaciu urografiu, cystoskopiu, vaginoskopiu a retrográdnu ureteropyelografiu. Vyšetreniami sme zistili raritne sa vyskytujúci triplexný močovod (II. typu podľa Smithovej klasifikácie) vľavo s ureter fissus dolného segmentu a naviac so sub-sfinkterickým ektopickým vyústením močovodu horného segmentu do uretry. Podozrenie na prítomnosť tretieho močovodu vzniklo potom, keď sme upresnili anatómiu ureteru dolného segmentu v zmysle ureter fissus pri klinicky jasnej ureterickej inkontinencii, aj prítomnej funkcii horného segmentu pri vylučovacej urografii. Ako terapeutický postup sme zvolili hemiureteronefrektómiu. Po výkone u dievčaťa prestal únik moču.
Continuous leakage of urine despite simultaneous normal micturition can be a sign of an ectopic ureter in girls. The case of 6 year old girl who suffered from continuous daylight and night time urine leakage is reported. Diagnosis and treatment of the child was done at the Clinic of paediatric urology. In diagnostics, we used sonography, excretory urography, cystoscopy, vaginoscopy and retrograde ureteropyelography. We found a rarely occurring triplex ureter on the left side and a sub-sphincteric ectopic ureter – with outlet into urethra. It was a case of ureteric incontinence. As a therapeutic approach, we chose hemiureteronephrectomy. In girl stopped urine leakage after surgery
- Klíčová slova
- ektopický močovod, triplexní močovod, ureterická inkontinence,
- MeSH
- dítě MeSH
- inkontinence moči etiologie chirurgie MeSH
- lidé MeSH
- nemoci močovodu * diagnóza chirurgie MeSH
- ureter abnormality chirurgie MeSH
- urologické chirurgické výkony metody MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
51 l. : grafy ; 32 cm
Project is focused on study of gene tergeted triplex forming oligonucleotides (TFO) and their conjugates with red-shifted wavelenghts photoactivable DNA-destructing molecules in anti-HIV gene therapy. The project is based on triplex terget sites in HIV provirus search,TFOs designing and evalution of binding and cleavage properties of TFOs in vitro and in cell culture by in project described methods.
Projekt je zaměřen na studium genově cílených triplax tvořících oligonukleotidů a jejich konjugátů s DNA-destrujícími molekulami aktivovatelnými blízce infračerveným zářením v genové terapii HIV infekce. Projekt je založen na vyhledávání vhodných sekvencí pro TFO v genomu proviru HIV,návrh TFO a studium vazebných a štěpících schopnosti TFO in vitro a v buněčné kultuře metodami blíže popsanými v tomto projektu.
MOTIVATION: Upgrade and integration of triplex software into the R/Bioconductor framework. RESULTS: We combined a previously published implementation of a triplex DNA search algorithm with visualization to create a versatile R/Bioconductor package 'triplex'. The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz. AVAILABILITY: R package 'triplex' is available from Bioconductor (bioconductor.org). CONTACT: lexa@fi.muni.cz SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein. The focus of this work is the structure-specific binding of p53 to DNA containing triplex-forming sequences in vitro and in cells and the effect on p53-driven transcription. This is the first DNA binding study of full-length p53 and its deletion variants to both intermolecular and intramolecular T.A.T triplexes. We demonstrate that the interaction of p53 with intermolecular T.A.T triplex is comparable to the recognition of CTG-hairpin non-B DNA structure. Using deletion mutants we determined the C-terminal DNA binding domain of p53 to be crucial for triplex recognition. Furthermore, strong p53 recognition of intramolecular T.A.T triplexes (H-DNA), stabilized by negative superhelicity in plasmid DNA, was detected by competition and immunoprecipitation experiments, and visualized by AFM. Moreover, chromatin immunoprecipitation revealed p53 binding T.A.T forming sequence in vivo. Enhanced reporter transactivation by p53 on insertion of triplex forming sequence into plasmid with p53 consensus sequence was observed by luciferase reporter assays. In-silico scan of human regulatory regions for the simultaneous presence of both consensus sequence and T.A.T motifs identified a set of candidate p53 target genes and p53-dependent activation of several of them (ABCG5, ENOX1, INSR, MCC, NFAT5) was confirmed by RT-qPCR. Our results show that T.A.T triplex comprises a new class of p53 binding sites targeted by p53 in a DNA structure-dependent mode in vitro and in cells. The contribution of p53 DNA structure-dependent binding to the regulation of transcription is discussed.
- MeSH
- aktivace transkripce genetika MeSH
- DNA vazebné proteiny chemie genetika MeSH
- DNA chemie genetika MeSH
- konformace nukleové kyseliny MeSH
- lidé MeSH
- nádorový supresorový protein p53 chemie genetika MeSH
- nukleotidové motivy genetika MeSH
- plazmidy genetika MeSH
- promotorové oblasti (genetika) MeSH
- regulační oblasti nukleových kyselin genetika MeSH
- sekvenční delece genetika MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
MOTIVATION: Current methods for identification of potential triplex-forming sequences in genomes and similar sequence sets rely primarily on detecting homopurine and homopyrimidine tracts. Procedures capable of detecting sequences supporting imperfect, but structurally feasible intramolecular triplex structures are needed for better sequence analysis. RESULTS: We modified an algorithm for detection of approximate palindromes, so as to account for the special nature of triplex DNA structures. From available literature, we conclude that approximate triplexes tolerate two classes of errors. One, analogical to mismatches in duplex DNA, involves nucleotides in triplets that do not readily form Hoogsteen bonds. The other class involves geometrically incompatible neighboring triplets hindering proper alignment of strands for optimal hydrogen bonding and stacking. We tested the statistical properties of the algorithm, as well as its correctness when confronted with known triplex sequences. The proposed algorithm satisfactorily detects sequences with intramolecular triplex-forming potential. Its complexity is directly comparable to palindrome searching. AVAILABILITY: Our implementation of the algorithm is available at http://www.fi.muni.cz/lexa/triplex as source code and a web-based search tool. The source code compiles into a library providing searching capability to other programs, as well as into a stand-alone command-line application based on this library. CONTACT: lexa@fi.muni.cz SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
- MeSH
- algoritmy MeSH
- chybné párování bází MeSH
- DNA chemie metabolismus MeSH
- Escherichia coli K12 genetika MeSH
- genom MeSH
- konformace nukleové kyseliny MeSH
- lidé MeSH
- obrácené repetice MeSH
- pravděpodobnostní funkce MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We have carried out extended set of μs-scale explicit solvent MD simulations of all possible G-triplexes which can participate in folding pathways of the human telomeric quadruplex. Our study accumulates almost 60 μs of simulation data, which is by about three orders of magnitude larger sampling compared to the earlier simulations of human telomeric G-DNA triplexes. Starting structures were obtained from experimental quadruplex structures by deleting either the first or the last strand. The life-times of antiparallel triplexes with lateral and diagonal loops are at least on μs-scale, which should be sufficient to contribute to the folding pathways. However, the triplex states may involve structures with various local deviations from the ideal triplexes, such as strand tilting and various alternative and incomplete triads. The simulations reveal easy rearrangements between lateral and diagonal loop triplex topologies. Propeller loops of antiparallel triplexes may to certain extent interfere with the G-triplexes but these structures are still viable candidates to participate in the folding. In contrast, all-parallel all-anti triplexes are very unstable and are unlikely to contribute to the folding. Although our simulations demonstrate that antiparallel G-triplexes, if folded, would have life-times sufficient to participate in the quadruplex folding, the results do not rule out the possibility that the G-triplexes are out-competed by other structures not included in our study. Among them, numerous possible misfolded structures containing guanine quartets can act as off-path intermediates with longer life-times than the triplexes. Besides analyzing the structural dynamics of a diverse set of G-DNA triplexes, we also provide a brief discussion of the limitations of the simulation methodology, which is necessary for proper understanding of the simulation data.
- MeSH
- DNA chemie MeSH
- G-kvadruplexy * MeSH
- konformace nukleové kyseliny * MeSH
- lidé MeSH
- nukleové kyseliny chemie genetika MeSH
- sekvence nukleotidů MeSH
- simulace molekulární dynamiky MeSH
- telomery chemie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- DNA genetika chemie MeSH
- mutace genetika MeSH
- oligonukleotidy genetika chemie MeSH
- oprava DNA imunologie MeSH
- regulace genové exprese imunologie MeSH
- Publikační typ
- přehledy MeSH
RNA triplexes are significant tertiary structure motifs that are found in many functional RNAs. Hence, small molecules capable of recognition, binding, and stabilization of the triple-helical RNA structures are emerging as attractive potential molecular biology tools and therapeutic agents. Here, we utilize methods of molecular biology and biophysics to study the interactions of a series of antitumor substitution-inert polynuclear platinum complexes (SI-PPCs) with triple-helical RNA structures. We show that SI-PPCs recognize and stabilize RNA triplexes and inhibit reverse transcription preferentially in the RNA template prone to the triplex formation. These so far unexplored properties of SI-PPCs suggest that the targeting of triple-stranded regions in RNA might contribute to the biological effects of SI-PPCs.
