207 research outputs found
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 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 , 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
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