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- MeSH
- avitaminóza diagnóza komplikace krev MeSH
- diagnostické techniky endokrinologické normy MeSH
- financování organizované MeSH
- konsensus MeSH
- lidé MeSH
- mutační analýza DNA metody MeSH
- parathormon krev MeSH
- primární hyperparatyreóza diagnóza genetika komplikace MeSH
- protoonkogenní proteiny genetika MeSH
- receptory "calcium-sensing" genetika MeSH
- vitamin D krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- souhrny MeSH
The authors of the article titled "Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine" (Dhanjal DS, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K, Chopra C. Curr Med Chem. 2024; 31(13): 1646-1690. DOI: 10.2174/0929867330666230503144619. PMID: 37138422) [1] have made revisions to the references in the text and the reference section. These updates have been made to ensure the integrity of the article. The updated reference list can be found in the latest version of the article. The authors apologize for any confusion or inconvenience caused. The original article can be found online at: https://www.eurekaselect.com/article/131443.
- MeSH
- lidé MeSH
- přeprogramování buněk * genetika MeSH
- regenerativní lékařství * MeSH
- vývojová biologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
After a presence of highly hepatotoxic and potentially carcinogenic N-nitrosodimethylamine was detected in certain lots of sartan, ranitidine, metformin, and other pharmaceuticals, local regulatory authorities issued recalls of suspected products, and concerns of the pharmacotherapy safety were widely discussed. Since then, testing of a representative sample of each produced lot of these pharmaceuticals is required as a part of quality control processes. Hence, an interface-free CE-nanoESI system coupled with MS detection was employed for the development of a simple and economical method for quantitative detection of this contaminant in the valsartan drug substances and finished formulations used as model matrices. In this arrangement, a fused-silica capillary was used as both a separation column and a nanoESI emitter providing high ionization efficiency and sensitivity. The optimized procedure was found to have sufficient selectivity, linearity, accuracy, and precision. The established LOD and LOQ values were 0.3 and 1.0 ng/mL, respectively. The practical applicability of the method was tested by analyses of commercially available Valsacor® tablets. The results obtained prove that the developed procedure represents a promising alternative to currently available GC- and LC-based methods. Furthermore, after an adjustment of the separation conditions, the CE-nanoESI/MS system can be conceptually used for the determination of NDMA in other suspected pharmaceuticals.
- MeSH
- dimethylnitrosamin analýza MeSH
- elektroforéza kapilární metody MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- kontaminace léku * MeSH
- lineární modely MeSH
- nanotechnologie MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- tablety MeSH
- valsartan chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Currently, 10 different amino acid variants of the HLA-DRB1*12 family are known. We here report the identification of a new HLA-DRB1*12 allele in a healthy Caucasian male individual. The allele was detected by sequencing-based typing during confirmatory high-resolution typing of an unrelated, male, potential donor from the Czech National Marrow Donors Registry. Compared with DRB1*120101, to which it is closest, the new variant is characterized by a new replacement mutation (T-->C) at nucleotide position 126 of exon 2, resulting in the amino acid substitution Phe-->Leu at position 47. Computational analysis reveals that position 47 functions as a keystone in the beta(1) domain, joining both segments of the alpha helix with the beta sheet, and plays a major role in the structural conformation of the binding groove. Additionally, position 47 is part of pocket E of the peptide binding groove and is directly involved in peptide binding. The new allele, DRB1*1211, is therefore likely to differ substantially from other DRB1*12 alleles in its peptide binding repertoire and alloreactive potential.
- MeSH
- běloši MeSH
- bodová mutace * MeSH
- HLA-DR antigeny chemie genetika imunologie MeSH
- HLA-DRB1 řetězec MeSH
- konformace proteinů MeSH
- krystalografie rentgenová MeSH
- lidé středního věku MeSH
- lidé MeSH
- substituce aminokyselin MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
R-loops are common non-B nucleic acid structures formed by a three-stranded nucleic acid composed of an RNA-DNA hybrid and a displaced single-stranded DNA (ssDNA) loop. Because the aberrant R-loop formation leads to increased mutagenesis, hyper-recombination, rearrangements, and transcription-replication collisions, it is regarded as important in human diseases. Therefore, its prevalence and distribution in genomes are studied intensively. However, in silico tools for R-loop prediction are limited, and therefore, we have developed the R-loop tracker tool, which was implemented as a part of the DNA Analyser web server. This new tool is focused upon (1) prediction of R-loops in genomic DNA without length and sequence limitations; (2) integration of R-loop tracker results with other tools for nucleic acids analyses, including Genome Browser; (3) internal cross-evaluation of in silico results with experimental data, where available; (4) easy export and correlation analyses with other genome features and markers; and (5) enhanced visualization outputs. Our new R-loop tracker tool is freely accessible on the web pages of DNA Analyser tools, and its implementation on the web-based server allows effective analyses not only for DNA segments but also for full chromosomes and genomes.
- MeSH
- algoritmy * MeSH
- DNA chemie genetika MeSH
- genomika metody MeSH
- internet statistika a číselné údaje MeSH
- lidé MeSH
- nestabilita genomu * MeSH
- R-smyčka * MeSH
- software MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Changes in the makeup of gut microbiota are linked to many neuropsychiatric diseases. Although the exact connection between gut dysbiosis and brain dysfunction is not yet fully understood, but recent data suggests that gut dysbiosis may contribute to the development of Alzheimer's disease (AD) by promoting neuroinflammation, insulin resistance, oxidative stress, and amyloid-beta (Aβ) aggregation. Gut dysbiosis in animal models is primarily characterized by an elevated ratio of Firmicutes/Bacteroidetes which may lead to the accumulation of amyloid precursor protein (APP) in the intestine, in the early stages of AD. Probiotics play a significant role in preventing against the symptoms of AD by restoring gut-brain homeostasis. This chapter provides an overview of the gut microbiota and its dysregulation in etiology of AD. Moreover, novel insights into alteration of the composition of gut microbiota as a preventive or therapeutic approach to AD are discussed.
Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stalled forks can resume DNA synthesis in a process initiated by MUS81 endonuclease, how TRC-associated G4/R-loops are removed to allow fork passage remains unclear. Here, we identify the mismatch repair protein MutSβ, an MLH1-PMS1 heterodimer termed MutLβ, and the G4-resolving helicase FANCJ as factors that are required for MUS81-initiated restart of DNA replication at TRC sites in human cells. This DNA repair process depends on the G4-binding activity of MutSβ, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutSβ, MutLβ, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutSβ, MutLβ, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.
- MeSH
- DNA-helikasy genetika metabolismus MeSH
- DNA genetika MeSH
- lidé MeSH
- proteiny FANC * genetika metabolismus MeSH
- R-smyčka * MeSH
- replikace DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) involves the propagation of filaments of tau protein throughout the cerebral cortex. Imaging tau filaments and oligomers in human brain at high resolution would help contribute insight into the mechanism and progression of tauopathic diseases. STED microscopy is a nano-scale imaging technique and we aimed to test the abilities of this method for resolving tau structures within human brain. Using autopsied 50μm AD brain sections, we demonstrate that STED microscopy can resolve immunolabelled tau filaments at 77nm resolution. Ribbon-like tau filaments imaged by STED appeared smooth along their axis with limited axial undulations. STED also resolved 70-80nm wide tau puncta. Of the fluorophores tested, STAR635p was optimal for STED imaging in this tissue. This was in part due to brain tissue autofluorescence within the lower wavelength ranges (488-590nm). Further, the stability and minimal photobleaching of STAR635p allowed STED z-stacks of neurons packed with tau filaments (neurofibrillary tangles) to be collated. There was no loss of x-y image resolution of individual tau filaments through the 20μm z-stack. This demonstrates that STED can contribute to nano-scale analysis and characterisation of pathologies within banked human autopsied brain tissue. Resolving tau structures at this level of resolution provides promising avenues for understanding mechanisms of pathology propagation in the different tauopathies as well as illuminating what contributes to disease heterogeneity.
- MeSH
- Alzheimerova nemoc diagnostické zobrazování patologie MeSH
- barvení a značení MeSH
- lidé MeSH
- neurofibrilární klubka patologie ultrastruktura MeSH
- optické zobrazování MeSH
- proteiny tau chemie ultrastruktura MeSH
- šedá hmota diagnostické zobrazování patologie MeSH
- zobrazování trojrozměrné MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81-LIG4-ELL pathway for resolution of R-loop-mediated transcription-replication conflicts, which may be involved in R-loop unwinding.
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
