162 research outputs found
Fast vaccine design and development based on correlates of protection (COPs): influenza as a trendsetter
Drug Delivery Technolog
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
Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses
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
Limits on Neutrino Emission from GRB 221009A from MeV to PeV using the IceCube Neutrino Observatory
Gamma-ray bursts (GRBs) have long been considered a possible source of
high-energy neutrinos. While no correlations have yet been detected between
high-energy neutrinos and GRBs, the recent observation of GRB 221009A - the
brightest GRB observed by Fermi-GBM to date and the first one to be observed
above an energy of 10 TeV - provides a unique opportunity to test for hadronic
emission. In this paper, we leverage the wide energy range of the IceCube
Neutrino Observatory to search for neutrinos from GRB 221009A. We find no
significant deviation from background expectation across event samples ranging
from MeV to PeV energies, placing stringent upper limits on the neutrino
emission from this source.Comment: Version in ApJ Letters Focus on the Ultra-luminous Gamma-Ray Burst
GRB 221009
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
Search for Extended Sources of Neutrino Emission in the Galactic Plane with IceCube
The Galactic plane, harboring a diffuse neutrino flux, is a particularly
interesting target to study potential cosmic-ray acceleration sites. Recent
gamma-ray observations by HAWC and LHAASO have presented evidence for multiple
Galactic sources that exhibit a spatially extended morphology and have energy
spectra continuing beyond 100 TeV. A fraction of such emission could be
produced by interactions of accelerated hadronic cosmic rays, resulting in an
excess of high-energy neutrinos clustered near these regions. Using 10 years of
IceCube data comprising track-like events that originate from charged-current
muon neutrino interactions, we perform a dedicated search for extended neutrino
sources in the Galaxy. We find no evidence for time-integrated neutrino
emission from the potential extended sources studied in the Galactic plane. The
most significant location, at 2.6 post-trials, is a 1.7 sized
region coincident with the unidentified TeV gamma-ray source 3HWC J1951+266. We
provide strong constraints on hadronic emission from several regions in the
Galaxy.Comment: 13 pages, 4 figures, 5 tables including an appendix. Accepted for
publication in Astrophysical Journa
Searches for Neutrinos from Large High Altitude Air Shower Observatory Ultra-high-energy γ-Ray Sources Using the IceCube Neutrino Observatory
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