The role of ribosomal protein networks in ribosome dynamics.

Accurate protein synthesis requires ribosomes to integrate signals from distant functional sites and execute complex dynamics. Despite advances in understanding ribosome structure and function, two key questions remain: how information is transmitted between these distant sites, and how ribosomal movements are synchronized? We recently highlighted the existence of ribosomal protein networks, likely evolved to participate in ribosome signaling. Here, we investigate the relationship between ribosomal protein networks and ribosome dynamics.

Asciminib resistance of a new BCR::ABL1 p.I293_K294insSSLRD mutant detected in a Ph + ALL patient.

Chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients largely benefit from an expanding tyrosine kinase inhibitors (TKIs) toolbox that has improved the outcome of both diseases. However, TKI success is continuously challenged by mutation-driven acquired resistance and therefore, close monitoring of clonal genetic diversity is necessary to ensure proper clinical management and adequate response to treatment. Here, we report the case of a ponatinib-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patient harboring a BCR::ABL1 p.

Preclinical Development of Magnetic Nanoparticles for Hyperthermia Treatment of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a very challenging disease with a very poor prognosis. It is characterized by a dense desmoplastic stroma that hampers drug penetration and limits the effectiveness of conventional chemotherapy (CT). As an alternative, the combination of CT with hyperthermia (HT) has been proposed as an innovative treatment modality for PDAC.

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.

[From the discovery of incretin hormones to GIP / GLP-1 / glucagon double and triple agonists].

The concept of treating diabetes with gut hormones was proposed in the early days of endocrinology (1902), but was not put into practice until the early 2000s. The discovery of the incretin effect (potentiation of insulin secretion when glucose is taken orally compared to intravenously) led to the discovery of the two main gut hormones responsible for this effect: GIP and GLP-1. The reduction of the incretin effect is directly involved in the pathogenesis of type 2 diabetes, which has led to the development of a series of innovative therapies such as GLP-1 analogues, GLP-1 receptor agonists, GIP/GLP-1 co-agonists and GIP/GLP-1/glucagon tri-agonists.

Separable roles of the DNA damage response kinase Mec1ATR and its activator Rad24RAD17 during meiotic recombination.

During meiosis, programmed DNA double-strand breaks (DSBs) are formed by the topoisomerase-like enzyme, Spo11, activating the DNA damage response (DDR) kinase Mec1ATR via the checkpoint clamp loader, Rad24RAD17. At single loci, loss of Mec1 and Rad24 activity alters DSB formation and recombination outcome, but their genome-wide roles have not been examined in detail. Here, we utilise two strategies-deletion of the mismatch repair protein, Msh2, and control of meiotic prophase length via regulation of the Ndt80 transcription factor-to help characterise the roles Mec1 and Rad24 play in meiotic recombination by enabling genome-wide mapping of meiotic progeny.

Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes.

The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule-severing enzymes, has emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins.

2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency.

Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance.

Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22 Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

Purpose: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL.

Patients And Methods: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870).

Adhesive and mechanical properties of the glue produced by 25 Drosophila species.

Drosophila glue, a bioadhesive produced by fly larvae to attach themselves to a substrate for several days, has recently gained attention for its peculiar adhesive and mechanical properties. Although Drosophila glue production was described more than 50 years ago, a general survey of the adhesive and mechanical properties of this proteinaceous gel across Drosophila species is lacking. To measure adhesion, we present here a protocol that is robust to variations in protocol parameters, pupal age and calculation methods.

Search for Time-Dependent CP Violation in D^{0}→π^{+}π^{-}π^{0} Decays.

A measurement of time-dependent CP violation in D^{0}→π^{+}π^{-}π^{0} decays using a pp collision data sample collected by the LHCb experiment in 2012 and from 2015 to 2018, corresponding to an integrated luminosity of 7.7  fb^{-1}, is presented. The initial flavor of each D^{0} candidate is determined from the charge of the pion produced in the D^{*}(2010)^{+}→D^{0}π^{+} decay.

Preventing the impact of solute adsorption in Taylor dispersion analysis: Application to protein and lipid nanoparticle analysis.

Taylor Dispersion Analysis (TDA) allows diffusion coefficient (D) or hydrodynamic radius (R) determination on a wide range of size between angstroms and about 300 nm. However, solute adsorption phenomena can affect the repeatability and reproducibility of TDA. Several numerical studies addressed the theoretical impact of solute adsorption in TDA, but very few experimental studies focus on this topic and no experimental methodologies were proposed so far to reduce the impact of adsorption in TDA.

Flecainide to Prevent Atrial Arrhythmia After Patent Foramen Ovale Closure: AFLOAT Study, A Randomized Clinical Trial.

Background: The real incidence of atrial arrhythmia (AA) after patent foramen ovale (PFO) closure and whether this complication can be prevented remain unknown. We assessed whether flecainide is effective to prevent AA during the first 3 months after PFO closure, and whether 6 months of treatment with flecainide is more effective than 3 months to prevent AA after PFO closure.

Methods: AFLOAT (Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Fibrillation or Tachycardia Trial) is a prospective, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the end points (PROBE [Prospective Randomized Open, Blinded End Point] design).

Search for Strange Quark Matter and Nuclearites on Board the International Space Station (SQM-ISS): A Future Detector to Search for Massive, Non-Relativistic Objects in Space.

SQM-ISS is a detector that will search from the International Space Station for massive particles possibly present among the cosmic rays. Among them, we mention strange quark matter, Q-Balls, lumps of fermionic exotic compact stars, Primordial Black Holes, mirror matter, Fermi balls, etc. These compact, dense objects would be much heavier than normal nuclei, have velocities of galaxy-bound systems, and would be deeply penetrating.

Incidence, Risk Factors, and Long-Term Outcomes for Extubation Failure in ICU in Patients With Obesity: A Retrospective Analysis of a Multicenter Prospective Observational Study.

Background: To our knowledge, no large observational study has compared the incidence and risk factors for extubation failure within 48 h and during ICU stay in the same cohort of unselected critically ill patients with and without obesity.

Research Question: What are the incidence and risk factors of extubation failure in patients with and without obesity?

Study Design And Methods: In the prospective multicenter observational Practices and Risk Factors for Weaning and Extubation Airway Failure in Adult Intensive Care Unit: A Multicenter Trial (FREEREA) study in 26 ICUs, the primary objective was to compare the incidence of extubation failure within 48 h in patients with and without obesity. Secondary objectives were to describe and to identify the independent specific risk factors for extubation failure using first a logistic regression model and second a decision tree analysis.

Multi-source connectivity as the driver of solar wind variability in the heliosphere.

The ambient solar wind that fills the heliosphere originates from multiple sources in the solar corona and is highly structured. It is often described as high-speed, relatively homogeneous, plasma streams from coronal holes and slow-speed, highly variable, streams whose source regions are under debate. A key goal of ESA/NASA's Solar Orbiter mission is to identify solar wind sources and understand what drives the complexity seen in the heliosphere.

Neck muscle vibration and prism adaptation fail to improve balance disturbances after stroke: A multicentre randomised controlled study.

Background: Pilot studies suggest potential effects of neck muscle vibration (NMV) and prism adaptation (PA) on postural balance disturbances related to spatial cognition.

Objectives: To evaluate the effect of 10 sessions of NMV and/or PA on ML deviation. We used the mediolateral centre of pressure position (ML deviation) as a biomarker for spatial cognition perturbation, hypothesising that PA and NMV would improve ML deviation, with a potential synergistic impact when used together.