Specificity and sensitivity of ALT-associated markers in cancer cells.

Some tumors employ a mechanism called alternative lengthening of telomeres (ALT) to counteract telomere shortening-induced replicative senescence. Several hallmarks are used to identify cell lines and tumors as ALT-positive. Here, we analyzed a panel of ALT-positive and -negative cancer cell lines to investigate the specificity and sensibility of ALT-associated markers.

Study of genotoxic and cytotoxic effects induced in human fibroblasts by exposure to pulsed and continuous 1.6 GHz radiofrequency.

Background: The widespread use of radiofrequency (RF) sources, ranging from household appliances to telecommunications devices and military equipment, raises concerns among people and regulatory agencies about the potential health risks of RF exposure. Consequently, several and studies have been done to investigate the biological effects, in particular non-thermal, of this non-ionizing radiation. To date, this issue is still being debated due to the controversial results that have been reported.

Coevolution of non-homologous end joining efficiency and encephalization.

Double-strand breaks (DSB), the most difficult to repair DNA damage, are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). Previous studies seem to indicate that primates, and particularly humans, have a better NHEJ system. A distinctive feature of the primate lineage (beside longevity) is encephalization, i.

Effects of p53 and ATRX inhibition on telomeric recombination in aging fibroblasts.

In order to avoid replicative senescence, tumor cells must acquire a telomere maintenance mechanism. Beside telomerase activation, a minority of tumors employs a recombinational mechanism called Alternative Lengthening of Telomeres (ALT). Several studies have investigated the potential ALT stimulation by inactivation of ATRX in tumor cells, obtaining contrasting results.

X-ray and DNA Damage: Limitations of the Dose as a Parameter for In Vitro Studies.

A century of studies has demonstrated that the magnitude of a radiation dose determines the extent of its biological effect. However, different types of radiation show different levels of effectiveness. Although all types of X-rays are usually considered to be equivalent, several authors have demonstrated an inverse relationship between photon energy and the biological effectiveness of the X-ray.

Inhibition of p53 and ATRX increases telomeric recombination in primary fibroblasts.

Telomere length can be maintained either by the telomerase enzyme or by alternative lengthening of telomeres (ALT), which is based on telomeric recombination. However, both mechanisms are inactive in most human somatic cells. ATRX has been previously identified as an ALT repressor gene.

Transcranial ultrasonography imaging of a suprasellar meningioma: A case description and technical notes.

Background: Computed tomography (CT) and magnetic resonance (MR) represent the gold standard for evaluating intracranial tumours, such as meningiomas; most meningiomas can be managed by surveillance and clinical follow-up, therefore, the ideal technology should be cheap, non-invasive, safe and able to reduce radiation exposure. Transcranial colour-coded duplex sonography (TCCS) can detect space-occupying lesions, but its full potential for clinical practice is still unexpressed.

Aims And Methods: We describe the ability of TCCS to directly and accurately image, in a 77-year-old woman hospitalised for septic shock and coma, a suprasellar meningioma with a spatial resolution very similar to CT.

TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection.

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase holoenzyme, which adds telomeric DNA repeats on chromosome ends to counteract telomere shortening. In addition, there is evidence of TERT non-canonical functions, among which is an antioxidant role. In order to better investigate this role, we tested the response to X-rays and HO treatment in hTERT-overexpressing human fibroblasts (HF-TERT).

PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment.

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified.

Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies.

A growing number of studies have evidenced non-telomeric functions of "telomerase". Almost all of them, however, investigated the non-canonical effects of the catalytic subunit TERT, and not the telomerase ribonucleoprotein holoenzyme. These functions mainly comprise signal transduction, gene regulation and the increase of anti-oxidative systems.

An integrated approach for chemical water quality assessment of an urban river stretch through Effect-Based Methods and emerging pollutants analysis with a focus on genotoxicity.

The impact of emerging chemical pollutants, on both status and functionality of aquatic ecosystems is worldwide recognized as a relevant issue of concern that should be assessed and managed by researchers, policymakers, and all relevant stakeholders. In Europe, the Reach Regulation has registered more than 100.000 chemical substances daily released in the environment.

Toxicological Comparison of Mancozeb and Zoxamide Fungicides at Environmentally Relevant Concentrations by an In Vitro Approach.

Mancozeb (MZ) and zoxamide (ZOX) are fungicides commonly used in pest control programs to protect vineyards. Their toxic and genotoxic potential were investigated in vitro on HepG2 and A549 cell lines at environmentally relevant concentrations. Cytotoxicity, apoptosis, necrosis and intracellular reactive oxygen species (ROS), comet assay and a micronucleus test with CREST immunofluorescence were used.

Growing and aging of hematopoietic stem cells.

In the hematopoietic system, a small number of stem cells produce a progeny of several distinct lineages. During ontogeny, they arise in the aorta-gonad-mesonephros region of the embryo and the placenta, afterwards colonise the liver and finally the bone marrow. After this fetal phase of rapid expansion, the number of hematopoietic stem cells continues to grow, in order to sustain the increasing blood volume of the developing newborn, and eventually reaches a steady-state.

The Multiple Facets of ATRX Protein.

ATRX gene codifies for a protein member of the SWI-SNF family and was cloned for the first time over 25 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability called Alpha Thalassemia/mental Retardation syndrome X-linked (ATRX) syndrome. Since its discovery as a helicase involved in alpha-globin gene transcriptional regulation, our understanding of the multiple roles played by the ATRX protein increased continuously, leading to the recognition of this multifaceted protein as a central "caretaker" of the human genome involved in cancer suppression. In this review, we report recent advances in the comprehension of the ATRX manifold functions that encompass heterochromatin epigenetic regulation and maintenance, telomere function, replicative stress response, genome stability, and the suppression of endogenous transposable elements and exogenous viral genomes.

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology.

The 2013/59/Euratom Directive reduced the occupational exposure limits for the lens. Since it has become crucial to estimate the dose absorbed by the lens, we have studied the individual variability of exposed workers' ocular conformations with respect to the data estimated from their personal dosimetry. The anterior eye conformations of 45 exposed workers were acquired using Scheimpflug imaging and classified according to their sight conditions (emmetropia, myopia or hypermetropia).

Functional analysis of p.ser605del variant: the aging phenotype of MDPL syndrome is associated with an impaired DNA repair capacity.

Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy define a rare systemic disorder, named MDPL Syndrome, due to almost always a variant in gene, encoding the DNA polymerase δ. We report a MDPL female heterozygote for the recurrent p.Ser605del variant.

DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation.

The current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial.

Human Fibroblasts In Vitro Exposed to 2.45 GHz Continuous and Pulsed Wave Signals: Evaluation of Biological Effects with a Multimethodological Approach.

The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and cytotoxic non-thermal effects have reported contradictory results that could be mainly due to inadequate experimental design and lack of well-characterized exposure systems and conditions. Moreover, a topic poorly investigated is related to signal modulation induced by electromagnetic fields.

G-quadruplex Stabilization Fuels the ALT Pathway in ALT-positive Osteosarcoma Cells.

Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10%-15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, as shown in telomerase-positive cancer models. Moreover, RHPS4 is also able to reduce cell proliferation in ALT cells, although the influence of G4 stabilization on the ALT mechanism has so far been poorly investigated.

Alternative Lengthening of Telomeres and Chromatin Status.

Telomere length is maintained by either telomerase, a reverse transcriptase, or alternative lengthening of telomeres (ALT), a mechanism that utilizes homologous recombination (HR) proteins. Since access to DNA for HR enzymes is regulated by the chromatin status, it is expected that telomere elongation is linked to epigenetic modifications. The aim of this review is to elucidate the epigenetic features of ALT-positive cells.

Quantitative relationships between acentric fragments and micronuclei: new models and implications for curve fitting.

To examine the phenomena governing the quantitative relationships between acentric fragments and micronuclei and understand which formulas are useful for curve-fitting of experimental data of micronuclei. A stochastic model, including the phenomena of inclusion, coalescence and culling out, was developed and applied to experimental data. Probabilities for inclusion/exclusion of acentric fragments into daughter nuclei and for coalescence of many fragments into a single micronucleus were found to be not cell type-specific.

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus.

Involvement of the central nervous system (CNS) is an uncommon feature in systemic lupus erythematosus (SLE), making diagnosis rather difficult and challenging due to the poor specificity of neuropathic symptoms and neurological symptoms. In this work, we used human-induced pluripotent stem cells (hiPSCs) derived from CNS-SLE patient, with the aim to dissect the molecular insights underlying the disease by gene expression analysis and modulation of implicated pathways. CNS-SLE-derived hiPSCs allowed us to provide evidence of Erk and Akt pathways involvement and to identify a novel cohort of potential biomarkers, namely CHCHD2, IDO1, S100A10, EPHA4 and LEFTY1, never reported so far.

Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability.