Structure of the pre-60S ribosomal subunit with nuclear export factor Arx1 bound at the exit tunnel

Pre-ribosomal particles evolve in the nucleus through transient interaction with biogenesis factors, before export to the cytoplasm. Here, we report the architecture of the late pre-60S particle purified from Saccharomyces cerevisiae through Arx1, a nuclear export factor with structural homology to methionine aminopeptidases, or its binding partner Alb1. Cryo-electron microscopy reconstruction of the Arx1-particle at 11.9 Å resolution reveals regions of extra densities on the pre-60S particle attributed to associated biogenesis factors, confirming the immature state of the nascent subunit. One of these densities could be unambiguously assigned to Arx1. Immuno-electron microscopy and UV cross-linking localize Arx1 close to the ribosomal exit tunnel in direct contact with ES27, a highly dynamic eukaryotic rRNA expansion segment. The binding of Arx1 at the exit tunnel may position this export factor to prevent premature recruitment of ribosome-associated factors active during translation

The GRANDMA network in preparation for the fourth gravitational-wave observing run

GRANDMA is a world-wide collaboration with the primary scientific goal ofstudying gravitational-wave sources, discovering their electromagneticcounterparts and characterizing their emission. GRANDMA involves astronomers,astrophysicists, gravitational-wave physicists, and theorists. GRANDMA is now atruly global network of telescopes, with (so far) 30 telescopes in bothhemispheres. It incorporates a citizen science programme (Kilonova-Catcher)which constitutes an opportunity to spread the interest in time-domainastronomy. The telescope network is an heterogeneous set of already-existingobserving facilities that operate coordinated as a single observatory. Withinthe network there are wide-field imagers that can observe large areas of thesky to search for optical counterparts, narrow-field instruments that dotargeted searches within a predefined list of host-galaxy candidates, andlarger telescopes that are devoted to characterization and follow-up of theidentified counterparts. Here we present an overview of GRANDMA after the thirdobserving run of the LIGO/VIRGO gravitational-wave observatories in $2019-2020$and its ongoing preparation for the forthcoming fourth observational campaign(O4). Additionally, we review the potential of GRANDMA for the discovery andfollow-up of other types of astronomical transients.<br

Mutant p53 as a guardian of the cancer cell

Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart. Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance. In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system. These activities of mutant p53 may explain cancer cell addiction to this particular oncogene, and their study may disclose tumor vulnerabilities and synthetic lethalities that could be exploited for hitting tumors bearing missense TP53 mutations

Ready for O4 II: GRANDMA Observations of Swift GRBs during eight-weeks of Spring 2022

We present a campaign designed to train the GRANDMA network and its infrastructure to follow up on transient alerts and detect their early afterglows. In preparation for O4 II campaign, we focused on GRB alerts as they are expected to be an electromagnetic counterpart of gravitational-wave events. Our goal was to improve our response to the alerts and start prompt observations as soon as possible to better prepare the GRANDMA network for the fourth observational run of LIGO-Virgo-Kagra (which started at the end of May 2023), and future missions such as SM. To receive, manage and send out observational plans to our partner telescopes we set up dedicated infrastructure and a rota of follow-up adcates were organized to guarantee round-the-clock assistance to our telescope teams. To ensure a great number of observations, we focused on Swift GRBs whose localization errors were generally smaller than the GRANDMA telescopes' field of view. This allowed us to bypass the transient identification process and focus on the reaction time and efficiency of the network. During 'Ready for O4 II', 11 Swift/INTEGRAL GRB triggers were selected, nine fields had been observed, and three afterglows were detected (GRB 220403B, GRB 220427A, GRB 220514A), with 17 GRANDMA telescopes and 17 amateur astronomers from the citizen science project Kilonova-Catcher. Here we highlight the GRB 220427A analysis where our long-term follow-up of the host galaxy allowed us to obtain a photometric redshift of $z=0.82\pm0.09$, its lightcurve elution, fit the decay slope of the afterglows, and study the properties of the host galaxy

A Search for Coincident Neutrino Emission from Fast Radio Bursts with Seven Years of IceCube Cascade Events

This paper presents the results of a search for neutrinos that are spatially and temporally coincident with 22 unique, non-repeating Fast Radio Bursts (FRBs) and one repeating FRB (FRB121102). FRBs are a rapidly growing class of Galactic and extragalactic astrophysical objects that are considered a potential source of high-energy neutrinos. The IceCube Neutrino Observatory's previous FRB analyses have solely used track events. This search utilizes seven years of IceCube's cascade events which are statistically independent of the track events. This event selection allows probing of a longer range of extended timescales due to the low background rate. No statistically significant clustering of neutrinos was observed. Upper limits are set on the time-integrated neutrino flux emitted by FRBs for a range of extended time-windows

Searches for Neutrinos from LHAASO ultra-high-energy {\gamma}-ray sources using the IceCube Neutrino Observatory

Galactic PeVatrons are Galactic sources theorized to accelerate cosmic rays up to PeV in energy. The accelerated cosmic rays are expected to interact hadronically with nearby ambient gas or the interstellar medium, resulting in {\gamma}-rays and neutrinos. Recently, the Large High Altitude Air Shower Observatory (LHAASO) identified 12 {\gamma}-ray sources with emissions above 100 TeV, making them candidates for PeV cosmic-ray accelerators (PeVatrons). While at these high energies the Klein-Nishina effect suppresses exponentially leptonic emission from Galactic sources, evidence for neutrino emission would unequivocally confirm hadronic acceleration. Here, we present the results of a search for neutrinos from these {\gamma}-ray sources and stacking searches testing for excess neutrino emission from all 12 sources as well as their subcatalogs of supernova remnants and pulsar wind nebulae with 11 years of track events from the IceCube Neutrino Observatory. No significant emissions were found. Based on the resulting limits, we place constraints on the fraction of {\gamma}-ray flux originating from the hadronic processes in the Crab Nebula and LHAASOJ2226+6057