I-motif formation in the promoter region of the B-MYB proto-oncogene.

Understanding the mechanisms of carcinogenesis is essential to combat cancer. The search for alternative targets for anticancer therapy has gained interest, particularly when focused on upstream pathways. This strategy is particularly relevant when the encoded target proteins are known - or believed - to be "undruggable", as has been reported for the B-MYB oncogene.

Human genomic DNA is widely interspersed with i-motif structures.

DNA i-motif structures are formed in the nuclei of human cells and are believed to provide critical genomic regulation. While the existence, abundance, and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescent staining, and more recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA have remained unclear. Here we utilise high-affinity i-motif immunoprecipitation followed by sequencing to map i-motifs in the purified genomic DNA of human MCF7, U2OS and HEK293T cells.

Production of the anti-G-quadruplex antibody BG4 for efficient genome-wide analyses: From plasmid quality control to antibody validation.

G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that can form at guanine-rich sequences of DNA and RNA in every kingdom of life. At the DNA level, G4s can form throughout genomes but they are prevalently found in promoter regions and at telomeres, and they have been attributed functions spanning from transcriptional regulation, to control of DNA replication, to maintenance of chromosome ends. Our understanding of the functions of G4s in cells has greatly improved with the development of specific anti-G4 antibodies, which allow the visualization of G4s by immunofluorescence but also the mapping of these secondary DNA structures genome wide.

Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells.

i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells.

Human Virus Genomes Are Enriched in Conserved Adenine/Thymine/Uracil Multiple Tracts That Pause Polymerase Progression.

The DNA secondary structures that deviate from the classic Watson and Crick base pairing are increasingly being reported to form transiently in the cell and regulate specific cellular mechanisms. Human viruses are cell parasites that have evolved mechanisms shared with the host cell to support their own replication and spreading. Contrary to human host cells, viruses display a diverse array of nucleic acid types, which include DNA or RNA in single-stranded or double-stranded conformations.

G-Quadruplex Targeting in the Fight against Viruses: An Update.

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key cellular processes, such as transcription and replication. Since their discovery, G4s have been mainly investigated for their role in cancer and as targets in anticancer therapy. More recently, exploration of the presence and role of G4s in viral genomes has led to the discovery of G4-regulated key viral pathways.

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1.

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication.

Deferoxamine mesylate improves splicing and GAA activity of the common c.-32-13T>G allele in late-onset PD patient fibroblasts.

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder due to deficient activity of the acid alpha glucosidase enzyme (GAA). As a consequence of the enzymatic defect, undigested glycogen accumulates within lysosomes. Most patients affected by the late-onset (LO) phenotype carry in at least one allele the c.

Comparative Effect of Two Red Lights on Biofilms and Assessment of Temperature Variances in Human Teeth During Photodynamic Antimicrobial Chemotherapy.

The goals of this investigation were to compare the effect of photodynamic antimicrobial chemotherapy (PACT) with two different red lights on biofilms, as well as to assess the temperature variances caused by PACT on human teeth. biofilms ( = 3) were grown on hydroxyapatite disks, and the antimicrobial effect of PACT was evaluated using toluidine blue O (100 μg/mL) associated with Laserbeam (LB 56.6 J/cm) and LumaCare™ (LC -56.

Twice-daily red and blue light treatment for Candida albicans biofilm matrix development control.

Phototherapy has been proposed as a direct means of affecting local bacterial infections. However, the use of phototherapy to prevent fungal biofilm development has received comparatively less attention. This study aimed to determine the effects of red light treatment and blue light treatment, without a photosensitizer, on the development of Candida albicans biofilm.

Trophic availability buffers the detrimental effects of clogging in an alpine stream.

Clogging, the streambed colmation by fine sediments, is an important widespread source of impact affecting freshwaters. Alterations in stream morphology and hydrology, added to the effects of global climate change, are responsible for this phenomenon, that is particularly pernicious in mountainous lotic systems naturally characterized by coarse substrates. Among the studies investigating this issue some were descriptive, while others used artificial substrates to compare ongoing fine sediment accumulation and macroinvertebrate assemblage recruitment.

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy.

An effective and highly regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5-]thiazolo[3,2-]-1,2,4-triazine-6,3'-pyrrolidine-2',3''-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5-]thiazolo[3,2-]-1,2,4-triazine moieties has been developed. The method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to 6-benzylideneimidazo[4,5-]thiazolo[3,2-]-1,2,4-triazine-2,7-diones.

Effect of Photodynamic Antimicrobial Chemotherapy on Mono- and Multi-Species Cariogenic Biofilms: A Literature Review.

Objective: The aim of this literature review is to study the effect of photodynamic antimicrobial chemotherapy (PACT) on mono- and multi-species cariogenic biofilms.

Methods: To this purpose, the database, PubMed, was searched using the descriptors, photodynamic therapy, antimicrobial photodynamic chemotherapy, and photoinactivation, associated with the mandatory presence of the word biofilm. A total of 98 references published from 2003 to 2016 were selected.

Occurrence and antimicrobial susceptibility of enteric rods and pseudomonads isolated from the dental prostheses biofilm.

Objective:: To determine the occurrence and the in vitro antimicrobial susceptibility of enteric rods and pseudomonads from the denture biofilm of 52 subjects at the Center for Dental Specialties of Sobral/ Ceara, Brazil.

Material And Methods:: Denture biofilm was collected and samples plated on MacConkey agar. The isolated bacterial colonies were identified using the BBL Crystal enteric/non-fermenter system.

Serratia marcescens resistance profile and its susceptibility to photodynamic antimicrobial chemotherapy.

Background: Some authors have reported the antimicrobial action of photodynamic antimicrobial chemotherapy (PACT) on bacteria related to nosocomial infections but there are few studies evaluating PACT on Serratia marcescens grown as planktonic cultures or as biofilms. The purpose of this study was to analyze the S. marcescens resistance profile and its susceptibility to PACT.

Photodynamic antimicrobial chemotherapy and ultraconservative caries removal linked for management of deep caries lesions.

Background: Ultraconservative removal of carious tissue is becoming increasingly highlighted for management of deep caries lesions, and combined with an antimicrobial photochemistry-based treatment modality (PACT), this approach can be enhanced favoring dental tissue repair and preservation. The aim was to investigate the effectiveness of PACT using a light emitting diode (LED) associated with a photosensitizer toluidine blue ortho (TBO) on deep caries lesions.

Methods: For that, a single blind, randomized, controlled, split-mouth clinical trial where 45 patients with at least two deep carious lesions on permanent posterior teeth was performed.

Effect of Twice-Daily Blue Light Treatment on Matrix-Rich Biofilm Development.

Background: The use of blue light has been proposed as a direct means of affecting local bacterial infections, however the use of blue light without a photosensitizer to prevent the biofilm development has not yet been explored. The aim of this study was to determine how the twice-daily treatment with blue light affects the development and composition of a matrix-rich biofilm.

Methodology/principal Findings: Biofilms of Streptococcus mutans UA159 were formed on saliva-coated hydroxyapatite discs for 5 days.

In situ assessment of effects of the bromide- and fluoride-incorporating adhesive systems on biofilm and secondary caries.

Aim: This in situ study assessed the effects of adhesive systems containing or not fluoride and/or the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on the microbiological composition of dental biofilm and enamel demineralization.

Materials And Methods: During two phases of 14 days, ten volunteers wore intraoral palatal appliances containing two slabs of human enamel according to a double-blind, crossover design. The slabs were randomly restored using a composite resin and one of the following adhesive systems: All-Bond SE(TM) (self-etch, fluoride/MDPB free adhesive, AB) and Clearfl Protect Bond (self-etch containing fluoride and MDPB adhesive, CB).

Functional characterization of the common c.-32-13T>G mutation of GAA gene: identification of potential therapeutic agents.

Glycogen storage disease type II is a lysosomal storage disorder due to mutations of the GAA gene, which causes lysosomal alpha-glucosidase deficiency. Clinically, glycogen storage disease type II has been classified in infantile and late-onset forms. Most late-onset patients share the leaky splicing mutation c.

A Comparative Study of the Photosensitizer Penetration into Artificial Caries Lesions in Dentin Measured by the Confocal Raman Microscopy.

This study utilized the confocal Raman microspectroscopy (CRM) technique for the first time to investigate the degree of the penetration of toluidine blue-orto (TBO) in artificial caries lesions produced by two distinct caries-inducing models. The dentin specimens (n = 10) were divided into three groups: control, in vitro and in situ. Thereafter, the lesion depth and the demineralization level were evaluated by cross-sectional microhardness (CSMH).

Characterization of antimicrobial photodynamic therapy-treated Streptococci mutans: an atomic force microscopy study.

Unlabelled: Abstract Objective: The aim of the present study was to examine the size and shape of Streptococcus mutans bacterial cells of infected dentin substrate subjected to photodynamic therapy (PDT) using atomic force microscopy (AFM).

Background Data: New trends in the application of AFM have been developed in the field of dentistry, making AFM a useful technique in high resolution imaging of biological structures and processes.

Materials And Methods: PDT was completed using an efficient light-emitting diode source (LED - λ=620-660 nm) with total light dose of 94 J/cm(2) in the presence of the photosensitizer toluidine blue O (TBO).

Effect of photodynamic antimicrobial chemotherapy on in vitro and in situ biofilms.

Aim: The effect of photodynamic antimicrobial chemotherapy (PACT) on oral biofilms was evaluated.

Methods: Biofilms formed in vitro were treated with sensitizer (S) and/or light (L) in the test (S+L+) and control (S-L-, S+L-, S-L+) groups. Additionally, 21 volunteers wore intraoral devices and the biofilms formed on each side of the device were referred to as S+L+ or S-L- groups.

Molecular analysis of HEXA gene in Argentinean patients affected with Tay-Sachs disease: possible common origin of the prevalent c.459+5A>G mutation.

Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the deficient activity of hexosaminidase A due to mutations in the HEXA gene. Up to date there is no information regarding the molecular genetics of TSD in Argentinean patients. In the present study we have studied 17 Argentinean families affected by TSD, including 20 patients with the acute infantile form and 3 with the sub-acute form.

Antimicrobial effect of chlorhexidine digluconate in dentin: In vitro and in situ study.

Aim: The aim of this study was to evaluate a very short-term in vitro and in situ effect of 2% chlorhexidine-digluconate-based (CHX) cavity cleanser on the disinfection of dentin demineralized by cariogenic bacteria.

Materials And Methods: Human dentin slabs were randomly allocated and used in 2 distinct phases, in vitro and in situ, for obtaining demineralized dentin. In vitro, the slabs (n=15) were immersed for 5 days in BHI broth inoculated with Streptococcus mutans CTT 3440.