Novel, tightly structurally related N-myristoyltransferase inhibitors display equally potent yet distinct inhibitory mechanisms.

N-myristoyltransferases (NMTs) catalyze essential acylations of N-terminal alpha or epsilon amino groups of glycines or lysines. Here, we reveal that peptides tightly fitting the optimal glycine recognition pattern of human NMTs are potent prodrugs relying on a single-turnover mechanism. Sequence scanning of the inhibitory potency of the series closely reflects NMT glycine substrate specificity rules, with the lead inhibitor blocking myristoylation by NMTs of various species.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

Background: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment.

Research Question: What are the most relevant changes in CT scan parameters over time for assessing response to treatment?

Study Design And Methods: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment.

Infection with Influenzavirus A in a murine model induces epithelial bronchial lesions and distinct waves of innate immune-cell recruitment.

Introduction: Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection.

Biochemical and structural analysis of N-myristoyltransferase mediated protein tagging.

N-terminal myristoylation is an essential eukaryotic modification crucial for cellular homeostasis in the context of many physiological processes. Myristoylation is a lipid modification resulting in a C14 saturated fatty acid addition. This modification is challenging to capture due to its hydrophobicity, low abundance of target substrates, and the recent discovery of unexpected NMT reactivity including myristoylation of lysine side chains and N-acetylation in addition to classical N-terminal Gly-myristoylation.

[Bacterial and fungal co-infection: an association of criminals to look for].

Introduction: Mucorales are fungi that cause opportunistic infections. Its incidence increases.

Case Report: We report case of a 68-year-old woman with myelodysplastic syndrome responsible for prolonged neutropenia, hospitalized for pneumonia and sinusitis caused by Pseudomonas aeruginosa.

Structural and Large-scale Analysis Unveil the Intertwined Paths Promoting NMT-catalyzed Lysine and Glycine Myristoylation.

N-myristoyltransferases (NMTs) catalyze protein myristoylation, a lipid modification crucial for cell survival and a range of pathophysiological processes. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs were recently shown to also modify lysine ε-amino groups (K-myristoylation). However, the clues ruling NMT-dependent K-myristoylation and the full range of targets are currently unknown.

A Continuous Assay Set to Screen and Characterize Novel Protein N-Acetyltransferases Unveils Rice General Control Non-repressible 5-Related N-Acetyltransferase2 Activity.

Protein N-acetyltransferases (NATs) belong to the general control non-repressible 5 (Gcn5)-related N-acetyltransferases (GNATs) superfamily. GNATs catalyze the transfer of acetyl from acetyl-CoA to the reactive amine moiety of a wide range of acceptors. NAT sequences are difficult to distinguish from other members of the GNAT superfamily and there are many uncharacterized GNATs.

Single-centre experience of transbronchial cryobiopsy as a first choice method for the diagnosis of interstitial lung disease.

Objectives: The diagnosis of interstitial lung disease is based on clinical and biological analysis associated with computed tomography (CT) pattern after discussion in multidisciplinary discussion. Lung transbronchial cryobiopsy has emerged with acceptable diagnostic reliability and low morbidity and mortality. The goal of our work is to describe our experience with lung cryobiopsy.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months.

Evaluation of prognostic scores for respiratory syncytial virus infection in a French multicentre cohort of allogeneic haematopoietic stem cell transplantation recipients.

Haematopoietic stem cell transplantation (HSCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. Two prognostic scores have been proposed to predict the risk of progression from upper respiratory tract infection (URTI) to lower respiratory tract infection (LRTI) and death. This was a multicentre study of allogeneic HSCT recipients diagnosed with an RSV infection between 2010 and 2019 who were retrospectively stratified by the immunodeficiency scoring index (ISI) and the severe immunodeficiency (SID) score.

Factors Associated With Aggressiveness of End-of-Life Care for Lung Cancer Patients and Associated Costs of Care.

Background: Results of previous studies demonstrated that high-intensity end-of-life (EOL) care improves neither cancer patients' survival nor quality of life. Our objective was to assess the incidence of and factors associated with aggressiveness of care during the last 30 days of life (DOL) of lung cancer (LC) patients and the impacts of aggressiveness of care in EOL-care costs.

Patients And Methods: Using French national hospital database, all patients with LC who died between January 1, 2010, and December 31, 2011, or between January 1, 2015, and January 31, 2016, were included.

Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases.

https://bit.ly/369ZGGu

High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation.

The promising drug target N-myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing high-resolution snapshots of the entire catalytic mechanism from the initial to final reaction states. Structural comparisons, together with biochemical analysis, provide unforeseen details about how NMT1 reaches a catalytically competent conformation in which the reactive groups are brought into close proximity to enable catalysis.

Scintigraphic Investigations of the Deep and Superficial Lymphatic Systems in the Evaluation of Lower Limb Oedema.

The lymphoscintigraphic investigation (LySc) of the superficial lymphatic system (SLS) remains the gold standard for the diagnosis of lower limb lymphoedema. However, LySc of the deep lymphatic system (DLS) may be useful for diagnosing deep lymphatic system insufficiency in patients with lower limb oedema (LLE) but normal and/or paradoxical LySc of the SLS. The purpose of this study was therefore to evaluate a new LySc of the deep lymphatic system in patients presenting with a normal and/or paradoxical SLS exam showing LLE.

Lung cancer and end-of-life care: a systematic review and thematic synthesis of aggressive inpatient care.

Objectives: Despite recent advances in thoracic oncology, most patients with metastatic lung cancer die within months of diagnosis. Aggressiveness of their end-of-life (EOL) care has been the subject of numerous studies. This study was undertaken to evaluate the literature on aggressive inpatient EOL care for lung cancer and analyse the evolution of its aggressiveness over time.

Evaluation of pneumococcal urinary antigen testing for respiratory tract infection investigations.

Objective: The pneumococcal urinary antigen test enables rapid bacteriological diagnosis in respiratory tract infections. The objective was to identify factors associated with a positive pneumococcal urinary antigen test result.

Patients And Methods: This seven-year retrospective monocentric study was performed on consecutive patients presenting with respiratory tract infections reported as pneumococcal-positive.

Health-Related Quality of Life Impact from Adding Bevacizumab to Cisplatin-Pemetrexed in Malignant Pleural Mesothelioma in the MAPS IFCT-GFPC-0701 Phase III Trial.

Purpose: The IFCT-GFPC-0701 MAPS phase III trial highlighted significant improvement in overall survival from adding bevacizumab to the standard first-line chemotherapy regimen [cisplatin plus pemetrexed (PC)] in advanced malignant pleural mesothelioma (MPM). We present the results of health-related quality of life (HRQoL), a secondary endpoint of MAPS.

Patients And Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and the lung cancer-specific module QLQ-LC13 at randomization and then every 9 weeks until disease progression.

Clinical Features of Mycobacterium canettii Infection: A Retrospective Study of 20 Cases Among French Soldiers and Relatives.

Background: Mycobacterium canettii forms part of the Mycobacterium tuberculosis complex. Mycobacterium canettii infections are mainly described in the Horn of Africa. The permanent presence of French soldiers in Djibouti raises the question of the risk of being infected with M.

Reliability and validity of the French version of the global physical activity questionnaire.

Background: The Global Physical Activity Questionnaire (GPAQ) has been used to measure physical activity (PA) and sedentary time in France, but no study has assessed its psychometric properties. This study aimed to compare the reliability as well as criterion and concurrent validity of the French version of the GPAQ with the French International Physical Activity Questionnaire long form (IPAQ-LF) and use of an accelerometer in a general adult population.

Methods: We included 92 participants (students or staff) from the Medicine Campus at the University of Lorraine, Nancy (north-eastern France).