The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Discovery of TeV γ-ray emission from the neighbourhood of the supernova remnant G24.7+0.6 by MAGIC

SNR G24.7+0.6 is a 9.5 kyrs radio and gamma-ray supernova remnant evolving in a dense medium. In the GeV regime, SNR G24.7+0.6 (3FHL J1834.1– 0706e/FGES J1834.1–0706) shows a hard spectral index (Γ∼2) up to 200 GeV, which makes it a good candidate to be observed with Cherenkov telescopes such as MAGIC. We observed the field of view of SNR G24.7+0.6 with the MAGIC telescopes for a total of 31 hours. We detect very high energy γ-ray emission from an extended source located 0.34 degree away from the center of the radio SNR. The new source, named MAGIC J1835–069 is detected up to 5 TeV, and its spectrum is well-represented by a power-law function with spectral index of 2.74 ± 0.08. The complexity of the region makes the identification of the origin of the very-high energy emission difficult, however the spectral agreement with the LAT source and overlapping position at less than 1.5 sigma point to a common origin. We analysed 8 years of Fermi-LAT data to extend the spectrum of the source down to 60 MeV. Fermi-LAT and MAGIC spectra overlap within errors and the global broad band spectrum is described by a power-law with exponential cutoff at 1.9 ± 0.5 TeV. The detected γ-ray emission can be interpreted as the results of proton-proton interaction between the supernova and the CO-rich surrounding

A cut-off in the TeV gamma-ray spectrum of the SNR Cassiopeia A

It is widely believed that the bulk of the Galactic cosmic rays is accelerated in supernova remnants (SNRs). However, no observational evidence of the presence of particles of PeV energies in SNRs has yet been found. The young historical SNR Cassiopeia A (Cas A) appears as one of the best candidates to study acceleration processes. Between 2014 December and 2016 October, we observed Cas A with the MAGIC telescopes, accumulating 158 h of good quality data. We derived the spectrum of the source from 100 GeV to 10 TeV. We also analysed 3c8 yr of Fermi-LAT to obtain the spectral shape between 60 MeV and 500 GeV. The spectra measured by the LAT and MAGIC telescopes are compatible within the errors and show a clear turn-off (4.6\u3c3) at the highest energies, which can be described with an exponential cut-off at E_c = 3.5(^{+1.6}_{-1.0})_{stat} (^{+0.8}_{-0.9})_{sys} TeV. The gamma-ray emission from 60 MeV to 10 TeV can be attributed to a population of high-energy protons with a spectral index of 3c2.2 and an energy cut-off at 3c10 TeV. This result indicates that Cas A is not contributing to the high energy ( 3cPeV) cosmic ray sea in a significant manner at the present moment. A one-zone leptonic model fails to reproduce by itself the multiwavelength spectral energy distribution. Besides, if a non-negligible fraction of the flux seen by MAGIC is produced by leptons, the radiation should be emitted in a region with a low magnetic field (B\u2a85180 \u3bcG) like in the reverse shock

Large Magnetoelectric Effects in Electrodeposited Nanoporous Microdisks Driven by Effective Surface Charging and Magneto Ionics

A synergetic approach to enhance magnetoelectric effects (i.e., control of magnetism with voltage) and improve energy efficiency in magnetically actuated devices is presented. The investigated material consists of an ordered array of Co–Pt microdisks, in which nanoporosity and partial oxidation are introduced during the synthetic procedure to synergetically boost the effects of electric field. The microdisks are grown by electrodeposition from an electrolyte containing an amphiphilic polymeric surfactant. The bath formulation is designed to favor the incorporation of oxygen in the form of cobalt oxide. A pronounced reduction of coercivity (88%) and a remarkable increase of Kerr signal amplitude (60%) are observed at room temperature upon subjecting the microdisks to negative voltages through an electrical double layer. These large voltage-induced changes in the magnetic properties of the microdisks are due to (i) the high surface-area-to-volume ratio with ultranarrow pore walls (sub-10 nm) that promote enhanced electric charge accumulation and (ii) magneto-ionic effects, where voltage-driven O^2– migration promotes a partial reduction of CoO to Co at room temperature. This simple and versatile procedure to fabricate patterned “nano-in-micro” magnetic motifs with adjustable voltage-driven magnetic properties is very appealing for energy-efficient magnetic recording systems and other magnetoelectronic devices