146 research outputs found

    Probing Free Nucleons With (Anti)Neutrinos

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    We discuss a method to study free protons and neutrons using ν(⊽)-hydrogen (H) Charged Current (CC) inelastic interactions, together with various precision tests of the isospin (charge) symmetry using ν and ⊽ CC interactions on both H and nuclear targets. Probing free nucleons with (anti)neutrinos provides information about their partonic structure, as well as a crucial input for the modeling of ν(⊽)-nucleus (A) interactions. Such measurements concurrently represent a valuable tool to address the main limitations of accelerator-based neutrino scattering experiments on nuclear targets, originating from the combined effect of the unknown (anti)neutrino energy and of the nuclear smearing. To this end, we present a method to impose constraints on nuclear effects and calibrate the (anti)neutrino energy scale in ν(⊽)- A interactions, which are two outstanding systematic uncertainties affecting present and future longbaseline neutrino oscillation experiments

    Nucleon axial-vector radius and form factor from future neutrino experiments

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    Precision measurements of antineutrino elastic scattering on hydrogen from future neutrino experiments offer a unique opportunity to access the low-energy structure of protons and neutrons. We discuss the determination of the nucleon axial-vector form factor and radius from antineutrino interactions on hydrogen which can be collected at the future Long-Baseline Neutrino Facility (LBNF), and study the sources of theoretical and experimental uncertainties. The projected accuracy would improve existing measurements by one order of magnitude and be competitive with contemporary lattice-QCD determinations, potentially helping to resolve the corresponding tension with measurements from (anti)neutrino elastic scattering on deuterium. We find that the current knowledge of the nucleon vector form factors could be one of the dominant sources of uncertainty. We also evaluate the constraints which can be simultaneously obtained on the absolute νˉμ\bar \nu_\mu flux normalization.Comment: 13 pages, 5 figure

    Altered telomere homeostasis and resistance to skin carcinogenesis in Suv39h1 transgenic mice

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    The Suv39h1 and Suv39h2 H3K9 histone methyltransferases (HMTs) have a conserved role in the formation of constitutive heterochromatin and gene silencing. Using a transgenic mouse model system we demonstrate that elevated expression of Suv39h1 increases global H3K9me3 levels in vivo. More specifically, Suv39h1 overexpression enhances the imposition of H3K9me3 levels at constitutive heterochromatin at telomeric and major satellite repeats in primary mouse embryonic fibroblasts. Chromatin compaction is paralleled by telomere shortening, indicating that telomere length is controlled by H3K9me3 density at telomeres. We further show that increased Suv39h1 levels result in an impaired clonogenic potential of transgenic epidermal stem cells and Ras/E1A transduced transgenic primary mouse embryonic fibroblasts. Importantly, Suv39h1 overexpression in mice confers resistance to a DMBA/TPA induced skin carcinogenesis protocol that is characterized by the accumulation of activating H-ras mutations. Our results provide genetic evidence that Suv39h1 controls telomere homeostasis and mediates resistance to oncogenic stress in vivo. This identifies Suv39h1 as an interesting target to improve oncogene induced senescence in premalignant lesions

    MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer

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    Target therapy; Telomeres; Triple-negative breast cancerTerapia dirigida; Telómeros; Cáncer de mama triple negativoTeràpia dirigida; Telòmers; Càncer de mama triple negatiuThe telomeric repeat-binding factor 2 (TRF2) is a telomere-capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti-cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA-based approach to reduce TRF2 expression. By performing a high-throughput luciferase screening of 54 candidate miRNAs, we identified miR-182-3p as a specific and efficient post-transcriptional regulator of TRF2. Ectopic expression of miR-182-3p drastically reduced TRF2 protein levels in a panel of telomerase- or alternative lengthening of telomeres (ALT)-positive cancer cell lines. Moreover, miR-182-3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR-182-3p impaired tumor growth in triple-negative breast cancer (TNBC) models, including patient-derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs-miR-182-3p were able to cross the blood–brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions.The research leading to these results has been funded by Italian Association for Cancer Research (AIRC # 21579) and Ministry of Health (CO-2019-12369662) to AB. This work was financially supported by Ministry of Health Ricerca Corrente 2022 and intramural grant-in-aid to EP. RD, LP and EP were supported by AIRC fellowships
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