Search results for "Heterocyclic Compounds"

2019

By using all atom molecular dynamics simulations, we studied the behavior of human DNA telomere sequences in guanine quadruplex (G4) conformation and in the presence of oxidative lesions, namely abasic sites. In particular, we evidenced that while removing one guanine base induces a significant alteration and destabilization of the involved leaflet, human telomere oligomers tend, in most cases, to maintain at least a partial quadruplex structure, eventually by replacing the empty site with undamaged guanines of different leaflets. This study shows that (i) the disruption of the quadruplex leaflets induces the release of at least one of the potassium cations embedded in the quadruplex channe…

Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.

2017

Background 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptiona…

Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells.

2018

Synaptic protein -synuclein (-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinsons disease. Here, we report that -SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also showthat premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking-SYN resemblesthe effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic -SYN. Interestingly…

Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis?

2017

International audience; Background: Moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis. Levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile.Objectives: To compare the in vivo activity of levofloxacin and moxifloxacin against M. tuberculosis strains with various levels of fluoroquinolone resistance.Methods: BALB/c mice were intravenously infected with 106M. tuberculosis H37Rv and three isogenic mutants: GyrA A90V, GyrB E540A and GyrB A543V. Treatment with 50 or 100 mg/kg levofloxacin and 60 or 66 mg/kg moxifloxacin was given orally every 6 h, for 4 we…

Effect of (−)-epigallocatechin gallate at different pH conditions on enteric viruses.

2017

Epigallocatechin gallate (EGCG), a flavonoid from green tea, is said to have extensive antimicrobial activity in a wide range of food spoilage or pathogenic fungi, yeast and bacteria. In this work, the antiviral activity of EGCG was assessed against hepatitis A virus (HAV) and murine norovirus (MNV), a human norovirus surrogate, at different temperatures, contact times and pH conditions by cell-culture methods. EGCG was effective in reducing the titers of HAV and MNV in a dose-dependent manner at neutral pH and 25 and 37 °C, while no effect was reported at 4 °C. HAV and MNV infectivity was completely removed after overnight treatment with EGCG at 2.5 mg/mL at 37 °C. Furthermore, results als…

In vivo effect of N-ethylmaleimide (NEM) on the measurement of nitrate in plasma

2016

Bioavailability of nitric oxide in the body may be estimated by measuring the concentration of nitrate in plasma. However, it has not been reported whether sequestering of aminothiols in plasma affects the concentration of nitrate in the samples.N-ethylmaleimide (NEM) sequesters aminothiols in plasma therefore we tested the in vivo effect of NEM on the concentration nitrate in plasma.Blood samples were collected from 56 healthy subjects in EDTA vials, EDTA vials containing PBS (pH7.4) and EDTA vials containing NEM dissolved in PBS. Nonparametric statistical tests were used to study the effect of NEM on the concentration of nitrate in plasma measured by the Griess reagent assay and by an HPL…

Fishing for G-quadruplexes in solution with a perylene diimide derivative labeled with biotins

2018

A new fluorescent, non‐cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G‐quadruplexes with scarce or no affinity towards single‐ or double‐stranded DNA. These features have made it possible to design a simple, effective, safe, cheap, and selective method for fishing G‐quadruplex structures in solution by use of PDI2B and streptavidin coated magnetic beads. The new cyclic method reported leads to the recovery of more than 80 % of G‐quadruplex structures from solution, even in the presence of an excess of single‐stranded or duplex DNA as competitors. Moreover, PDI2B is a G4 ligand that…

Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders

2020

A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of dive…

Epigenetic Modulation of Chromatin States and Gene Expression by G-Quadruplex Structures

2020

G-quadruplexes are four-stranded helical nucleic acid structures formed by guanine-rich sequences. A considerable number of studies have revealed that these noncanonical structural motifs are widespread throughout the genome and transcriptome of numerous organisms, including humans. In particular, G-quadruplexes occupy strategic locations in genomic DNA and both coding and noncoding RNA molecules, being involved in many essential cellular and organismal functions. In this review, we first outline the fundamental structural features of G-quadruplexes and then focus on the concept that these DNA and RNA structures convey a distinctive layer of epigenetic information that is critical for the c…

DNA structure-specific sensitization of a metalloporphyrin leads to an efficient in vitro quadruplex detection molecular tool

2016

International audience; The search for convenient molecular probes for detecting DNA and RNA quadruplexes in vitro is marked by a rapid pace of progress, spurred on by the multiple roles these higher-order nucleic acid structures play in many genetic dysregulations. Here, we contribute to this search, reporting on a palladated porphyrin named Pd.TEGPy: its efficiency as quadruplex-selective fluorescent dye relies on a structural design that endows it with attractive supramolecular and electronic properties and makes it an efficient turn-on, quadruplex-selective fluorescent stain thanks to a DNA-mediated sensitization mechanism that ensures a high level of specificity.