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.

Bacterial community composition of Hungarian salt-affected soils under different land uses.

Salinization and sodification are serious and worldwide growing threats to healthy soil functions. Although plants developed a plethora of traits to cope with high salinity, soil bacteria are also essential players of the adaptation process. However, there is still lack of knowledge on how other biotic and abiotic factors, such as land use or different soil properties, affect the bacterial community structure of these soils.

Prediction of response to neoadjuvant chemotherapy by MammaTyper® across breast cancer subtypes: A retrospective cross-sectional study.

Background: Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics.

Methods: Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed.

Pathological narcissism and relationship obsessive-compulsive disorder (ROCD) symptoms: Exploring the role of vulnerable narcissism.

Objective: Relationship obsessive-compulsive disorder (ROCD) symptoms, which include obsessive preoccupation, doubts, and compulsive behaviors focusing on the suitability of the relationship and/or partner, have been receiving increasing clinical, theoretical, and empirical attention. This clinical variant of OCD is associated with significant functional, personal, and dyadic consequences. ROCD symptoms have also been linked to several cognitive vulnerability factors, such as maladaptive relationship catastrophization.

Microaggression toward LGBTIQ people and implications for mental health: A systematic review.

Background: Research suggests that microaggressions detrimentally impact the mental health of members of marginalized social groups.

Aims: The aim of this systematic review was to assess the exposure to microaggressions and related implications on mental health of Lesbian, Gay, Bisexual, Transgender, Intersex, and Queer (LGBTIQ) people.

Method: Medline, Scopus, PsycINFO, CINAHL, and EMBASE were searched until January 2023.

Post-traumatic stress disorder among LGBTQ people: a systematic review and meta-analysis.

Aims: Lesbian, gay, bisexual, transgender and queer people (LGBTQ) are at increased risk of traumatization. This systematic review aimed to summarize data regarding the risk of post-traumatic stress disorder (PTSD) for LGBTQ people and their subgroups.

Methods: Medline, Scopus, PsycINFO and EMBASE were searched until September 2022.

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).

Could We Safely Avoid a Second Resection in Selected Patients With T1 Non-Muscle-Invasive Bladder Cancer? Preliminary Results of Cost-Effectiveness Study From HUmanitas New Indications for ReTUR (HuNIRe) Multicenter Prospective Trial.

Objectives: The aim of this study is to assess whether restaging transurethral resection (ReTUR) could be safely replaced with urine cytology (UC) and in-office fiexible cystoscopy in selected T1 non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: This is an ongoing prospective multicenter trial enrolling patients diagnosed with T1 BC from 5 Italian centers. Patients with a macroscopically incomplete initial resection or absence of detrusor muscle were subjected to ReTUR according to European Association of Urology (EAU) guidelines.

The S-adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening.

Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation.

Atomic Force Microscopy Reveals that the Drosophila Telomere-Capping Protein Verrocchio Is a Single-Stranded DNA-Binding Protein.

Atomic force microscopy (AFM) is a scanning probe technique that allows visualization of biological samples with a nanometric resolution. Determination of the physical properties of biological molecules at a single-molecule level is achieved through topographic analysis of the sample adsorbed on a flat and smooth surface. AFM has been widely used for the structural analysis of nucleic acid-protein interactions, providing insights on binding specificity and stoichiometry of proteins forming complexes with DNA substrates.

A novel deterministic forecast model for COVID-19 epidemic based on a single ordinary integro-differential equation.

In this paper, we present a new approach to deterministic modelling of COVID-19 epidemic. Our model dynamics is expressed by a single prognostic variable which satisfies an integro-differential equation. All unknown parameters are described with a single, time-dependent variable ().

Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation.

Biogenesis of the human telomerase RNA (hTR) involves a complex series of posttranscriptional modifications, including hypermethylation of the 5' mono-methylguanosine cap to a tri-methylguanosine cap (TMG). How the TMG cap affects hTR maturation is unknown. Here, we show that depletion of trimethylguanosine synthase 1 (TGS1), the enzyme responsible for cap hypermethylation, increases levels of hTR and telomerase.

BODIPY-functionalized 1,10-phenanthroline as a long wavelength sensitizer for near-infrared emission of the ytterbium(iii) ion.

Two BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) moieties were chemically appended to the 4,7-positions of 1,10-phenanhtroline resulting in two new ligands (BODIPY-Phen and 4I-BODIPY-Phen) with strong absorption at 507 nm and 540 nm, respectively. BODIPY-Phen emits fluorescence strongly centered at 507 nm, whereas the fluorescence of 4I-BODIPY-Phen was completely quenched due to the introduction of four I atoms at its 2,6 positions. The two ligands reacted readily with tris(1,1,1,5,5,5-hexafluoro-2,4-pentanedionate) ytterbium(iii) dihydrate through substitution reactions forming eight-coordinate complexes that emit strongly at 976 nm upon excitation at their absorption maximal positions.

Ten daily fractions for partial breast irradiation. Long-term results of a prospective phase II trial.

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early-stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5-year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions.

Natural Aromatic Compounds as Scaffolds to Develop Selective G-Quadruplex Ligands: From Previously Reported Berberine Derivatives to New Palmatine Analogues.

In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are presented here for the first time. In detail, these palmatine derivatives were developed by inserting seven different small peptide basic chains, giving several new compounds that have never been reported before.

Seven fractions to deliver partial breast irradiation: the toxicity is Low.

Purpose: To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction).

Materials And Methods: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma.

WDR79/TCAB1 plays a conserved role in the control of locomotion and ameliorates phenotypic defects in SMA models.

SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion.

Multiple chromophobe and clear cell renal cancer in a patient affected by Birt-Hogg-Dubè syndrome: a case report.

Objectives: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The syndrome is linked to mutations in the FLCN gene, which is preferentially expressed in the skin, kidney, and lung. The aim of our paper is to describe a case of multiple bilateral renal cancer in a patient affected by BHDS.

The Drosophila telomere-capping protein Verrocchio binds single-stranded DNA and protects telomeres from DNA damage response.

Drosophila telomeres are sequence-independent structures maintained by transposition to chromosome ends of three specialized retroelements rather than by telomerase activity. Fly telomeres are protected by the terminin complex that includes the HOAP, HipHop, Moi and Ver proteins. These are fast evolving, non-conserved proteins that localize and function exclusively at telomeres, protecting them from fusion events.

Evidence for a quadruplex structure in the polymorphic hs1.2 enhancer of the immunoglobulin heavy chain 3' regulatory regions and its conservation in mammals.

Regulatory regions in the genome can act through a variety of mechanisms that range from the occurrence of histone modifications to the presence of protein-binding loci for self-annealing sequences. The final result is often the induction of a conformational change of the DNA double helix, which alters the accessibility of a region to transcription factors and consequently gene expression. A ∼300 kb regulatory region on chromosome 14 at the 3' end (3'RR) of immunoglobulin (Ig) heavy-chain genes shows very peculiar features, conserved in mammals, including enhancers and transcription factor binding sites.

Perylene and coronene derivatives binding to G-rich promoter oncogene sequences efficiently reduce their expression in cancer cells.

A novel approach to cancer therapeutics is emerging in the field of G-quadruplex (G4) ligands, small molecules designed to stabilize four-stranded structures that can form at telomeres as well as in other genomic sequences, including oncogene promoter sequences, 5'-UTR regions and introns. In this study, we investigated the binding activity of perylene and coronene derivatives PPL3C, CORON and EMICORON to G4 structures formed within the promoter regions of two important cancer-related genes, c-MYC and BCL-2, and their biochemical effects on gene and protein expression. In order to fully characterize the ability of the selected ligands to bind and stabilize the G4 structures originated by the c-MYC and BCL-2 promoter sequences, we performed electrospray ionization mass spectrometry (ESI-MS), Fluorescence Resonance Energy Transfer (FRET) measurements, Circular Dichroism (CD) spectra and polymerase stop assay.

AKTIP/Ft1, a New Shelterin-Interacting Factor Required for Telomere Maintenance.

Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes from incomplete replication, degradation and detection as DNA breaks. Mammalian telomeres are protected by shelterin, a multiprotein complex that binds the TTAGGG telomeric repeats and recruits a series of additional factors that are essential for telomere function. Although many shelterin-associated proteins have been so far identified, the inventory of shelterin-interacting factors required for telomere maintenance is still largely incomplete.

TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization.

The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats.