Knockdown of DOM/Tip60 complex subunits impairs male meiosis of Drosophila melanogaster

ATP-dependent chromatin remodeling complexes are involved in nucleosome sliding and eviction and/or the incorporation of histone variants into chromatin to facilitate several cellular and biological processes, including DNA transcription, replication and repair. The DOM/TIP60 chromatin remodeling complex of Drosophila melanogaster contains 18 subunits, including the DOMINO (DOM), an ATPase that catalyzes the exchange of the canonical H2A with its variant (H2A.V), and TIP60, a lysine-acetyltransferase that acetylates H4, H2A and H2A.V histones. In recent decades, experimental evidence has shown that ATP-dependent chromatin remodeling factors, in addition to their role in chromatin organization, have a functional relevance in cell division. In particular, emerging studies suggested the direct roles of ATP-dependent chromatin remodeling complex subunits in controlling mitosis and cytokinesis in both humans and D. melanogaster. However, little is known about their possible involvement during meiosis. The results of this work show that the knockdown of 12 of DOM/TIP60 complex subunits generates cell division defects that, in turn, cause total/partial sterility in Drosophila males, providing new insights into the functions of chromatin remodelers in cell division control during gametogenesis

Targeted protein degradation tools: overview and future perspectives

Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Resolving the origin of very-high-energy gamma-ray emission from the PeVatron candidate SNR G106.3+2.7 using MAGIC telescopes

The supernova remnant (SNR) G106.3+2.7 associated with a 100 TeV gamma-ray source reported by HAWC, Tibet ASγ, and LHAASO Collaborations is one of the promising PeVatron candidates. Because the SNR contains an energetic pulsar wind nebula (PWN) dubbed Boomerang powered by the pulsar PSR J2229+6114, it is unclear whether the gamma-ray emission originates from the SNR or PWN complex and whether it is caused by hadronic or leptonic processes. We observed gamma rays above 200 GeV in the vicinity of the SNR G106.3+2.7 using the MAGIC telescopes for total ∼ 120 hours between May 2017 and August 2019 with an angular resolution of 0.07– 0.10 degrees, achieving an unprecedented exposure for this object at these energies. An extended gamma-ray emission spatially correlated with the radio continuum emission at the head and tail of SNR G106.3+2.7 was detected using the MAGIC telescopes. We found a significant gamma-ray emission above 5.65 TeV only from the SNR tail region, while no significant emission in the same band is found at the SNR head region containing the Boomerang PWN. Therefore, the gamma rays above 10 TeV detected with the air shower experiments are, likely, mainly emitted from the SNR tail region. In this presentation, we discuss the morphology of the gamma-ray emission from this complex region and attempt self-consistent multi-wavelength modeling of the energy spectrum

Analysis of the W 44 Supernova Remnant and its surroundings with Fermi-LAT and MAGIC

The well-known supernova remnant (SNR) W 44 is observed in high-energy gamma rays and widely studied to investigate cosmic ray (CR) acceleration. Several analyses of the W 44 sur- roundings showed the presence of gamma-ray emission offset from the radio SNR shell. This emission is thought to originate from escaped high-energy CRs. We present a detailed analysis of the W 44 region as seen by Fermi-LAT, focusing on the spatial and spectral characteristics of both W 44 SNR and its surroundings. The spatial analysis was limited to energies above 1 GeV in order to exploit the improved angular resolution of the instrument, deriving a detailed description of the region morphology. Observations of the north-western region of W 44, also known as SRC-1 from previous works, were conducted with the MAGIC telescopes in the very high-energy gamma-ray band. We analysed MAGIC data exploiting the spatial information derived with the Fermi-LAT analysis at GeV energies. Here we show the results of both analyses and the combined Fermi-LAT and MAGIC spectra, thus obtaining constraining information on the diffusion of the escaped CRs

MAGIC detection of Geminga: an Inverse Compton tail?

We report the detection of pulsed emission from the Geminga pulsar (PSR J0633+1746) with the MAGIC telescopes. After the Crab and Vela pulsars, Geminga is the third pulsar detected in the very-high-energy domain, and its estimated age of 340 ky makes it the oldest one. The spectrum derived by MAGIC extends from 15 GeV to 75 GeV and can be modeled by a power-law function with spectral index Γ = 5.62 ± 0.54. Joint fits to MAGIC and Fermi-LAT data disfavour the existence of a sub-exponential cut-off in this energy range. Our results are discussed in the framework of the outer gap pulsar model. The measured power-law emission can be interpreted as the transition from curvature radiation to inverse Compton (IC) scattering of charges accelerated in the northern outer gap. The IC component is expected to continue towards higher energies. These results have been published in Acciari et al. 202

Shedding light on the highest energy emission from GRBs with MAGIC observations

On 14th January 2019, the MAGIC collaboration achieved the first significant detection at TeV energies of a gamma-ray burst (GRB), namely GRB 190114C. This observation sets the first experimental proof of very high energy (VHE, > 100 GeV) gamma-ray emission in GRBs, after more than 50 years from the first GRB detection and many searches with Cherenkov telescopes in the last decades. The data collected by MAGIC and by more than 20 other ground-based and space- borne instruments, spanning 17 orders of magnitude in energy, revealed a new GeV-TeV emission component in the GRB afterglow. This unprecedented multi-wavelength dataset, including VHE data for the first time, allowed a detailed study of the broadband emission. A one-zone synchrotron- self Compton scenario with internal γ-γ absorption could be used to describe the broadband emission, using parameters compatible with those found in previous studies of GRB afterglows below the GeV energy range. This detection opened a new era in the studies of GRBs, leading to new questions such as the universality of TeV emission in different types of GRBs. In this contribution, we will present the GRB follow-up program performed by the MAGIC collaboration, which started more than 15 years ago. We will highlight the results on GRB 190114C, discuss the implications for GRB physics, and report the latest developments and the prospects for future observations of GRBs with the MAGIC telescopes

Upper limits on the very high energy emission from GRBs observed by MAGIC

The MAGIC collaboration has developed a dedicated observational strategy to repoint rapidly towards gamma-ray bursts (GRBs). In this contribution we present the information extracted from the large sample of the GRBs observed by MAGIC from 2013 to 2019. None of these GRBs were significantly detected, and this study aims to shed light on the reasons behind those non-detections. The same strategy had led to the successful detection of two GRBs at Very High Energies (VHE, E > 100 GeV). We describe the details of the MAGIC GRB observational procedure and the general properties of each observed GRB. The lack of detection can be attributed either to unfavourable conditions or GRB intrinsic properties, such as the magnetic field’s energy density, the bulk Lorentz factor, or the emitting region’s size. For the presented sample of GRBs, we show the methods used to obtain flux upper limits in the VHE range, and propose physical implications of the non-detection of VHE emission. These results constitute an essential reference point to study the broadband emission of GRBs, and for the Cherenkov telescope community to organize future follow-ups of GRBs at VHE energies

Multi-messenger characterization of Mrk501 during historically low X-ray and gamma-ray activity

Blazars, together with other active galactic nuclei, are the most luminous persistent sources in our universe; and therefore a prime candidate for very-high-energy (>0.2 TeV, VHE) gamma-ray observations. For the two MAGIC telescopes, the Mrk501 galaxy is among the brightest observed blazars due to its proximity. We report a multi-wavelength and multi-messenger study of Mrk501 with data from 2017 to 2020, when Mrk501 showed a VHE flux typically below 10% that of the Crab Nebula. During this time, we performed three long observations with NuSTAR, which characterized the hard X-ray emission during three different low-activity flux levels. This Mrk501 dataset provided the unprecedented opportunity to study multi-wavelength variability and correlations with sensitive instruments during historically low X-ray and VHE gamma-ray emission (below 5% of the Crab Nebula flux in the VHE range), which could be considered as the baseline emission of Mrk501. We complemented the broadband spectral energy distributions (SED) of the identified historically low X-ray and VHE gamma-ray flux with data published by IceCube, in order to evaluate the potential existence of a hadronic component that is stable (or slowly variable), and less visible than the leptonic component that may dominate the emission during typical and flaring activity. In this contribution, we will also describe the evolution of the broadband SED comparing different theoretical scenarios