Adaptive trade-offs between vertebrate defence and insect predation drive Amazonian ant venom evolution.

Stinging ants have diversified into various ecological niches, and selective pressures may have contributed to shape the composition of their venom. To explore the drivers underlying venom variation in ants, we sampled 15 South American rainforest species and recorded a range of traits, including ecology, morphology and venom bioactivities. Principal component analysis of both morphological and venom bioactivity traits reveals that stinging ants display two functional strategies where species have evolved towards either an exclusively offensive venom or a multi-functional venom.

Isolation, NMR Characterization, and Bioactivity of a Flavonoid Triglycoside from Stems: Antioxidant and Antiproliferative Effects on MDA-MB-231 Breast Cancer Cells.

Plant extracts are considered as a large source of active biomolecules, especially in phytosanitary and pharmacological fields. is a woody Saharan plant located in the big desert of North Africa. Our previous research paper proved the richness of the methanol extract obtained from the stems in flavonoids and phenolic compounds as well as its remarkable antioxidant activity.

Individualized throughput metric reports for emergency medicine residents: Impact on time to disposition and resident perceptions.

Background: Research suggests that quantitative metric reports can improve the clinical performance of emergency physicians; however, few studies have examined their effects on physicians in training. The primary study objective was to assess the effects of providing emergency medicine (EM) residents with individualized throughput metrics with regard to emergency department (ED) disposition times.

Methods: We performed a single-center, retrospective, observational study from January 2021 to December 2022 examining ED disposition times before and after providing upper-level EM residents individualized throughput metrics.

Prognostic value of 18 FDG-PET at diagnosis and follow-up in giant cell arteritis: An observational restrospective study.

Objectives: To evaluate the ability of FDG PET/CT, at diagnosis of giant cell arteritis (GCA) and during follow-up, to predict occurrence of relapse in large-vessel GCA (LV-GCA).

Methods: We conducted a retrospective study using the French Study Group for Large-Vessel Vasculitis (GEFA) network. Data from patients with LV-GCA diagnosed by PET/CT and who had PET/CT in the following year were collected.

Discovery of an Insect Neuroactive Helix Ring Peptide from Ant Venom.

Ants are among the most abundant terrestrial invertebrate predators on Earth. To overwhelm their prey, they employ several remarkable behavioral, physiological, and biochemical innovations, including an effective paralytic venom. Ant venoms are thus cocktails of toxins finely tuned to disrupt the physiological systems of insect prey.

A synthetic delivery vector for mucosal vaccination.

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8 T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB.

Engineered Synthetic STxB for Enhanced Cytosolic Delivery.

Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules are generally not able to spontaneously translocate across membranes to reach these cytosolic targets. Therefore a strong need exists for tools that enhance cytosolic delivery.

The mechanism underlying toxicity of a venom peptide against insects reveals how ants are master at disrupting membranes.

Hymenopterans represent one of the most abundant groups of venomous organisms but remain little explored due to the difficult access to their venom. The development of proteo-transcriptomic allowed us to explore diversity of their toxins offering interesting perspectives to identify new biological active peptides. This study focuses on U function, a linear, amphiphilic and polycationic peptide isolated from ant venom.

The multi-faceted nature of 15 CFTR exonic variations: Impact on their functional classification and perspectives for therapy.

Background: The majority of variants of unknown clinical significance (VUCS) in the CFTR gene are missense variants. While change on the CFTR protein structure or function is often suspected, impact on splicing may be neglected. Such undetected splicing default of variants may complicate the interpretation of genetic analyses and the use of an appropriate pharmacotherapy.

Infection Risk in Patients with Dermatomyositis Associated with Anti-MDA5 Antibodies: A Historical Cohort Study.

Objective: Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population.

High-Relaxivity Molecular MRI Contrast Agent to Target Gb3-Expressing Cancer Cells.

Targeted contrast agents (CAs) can improve magnetic resonance imaging (MRI) for accurate cancer diagnosis. In this work, we used the Shiga toxin B-subunit (STxB) as a targeting agent, which binds to Gb3, a glycosphingolipid highly overexpressed on the surface of tumor cells. We developed STxB-targeted MRI probes from cyclic peptide scaffolds functionalized with six to nine monoamide DO3A[Gd(III)] chelates.

A qualitative assessment of emergency medicine residents' receptivity to feedback.

Background: Effective feedback is the cornerstone of competency-based education. The emergency department (ED) is a unique learning and feedback environment. Developing our understanding of emergency medicine (EM) residents' experiences around feedback will improve resident training and inform EM faculty development programs.

The rescue of F508del-CFTR by elexacaftor/tezacaftor/ivacaftor (Trikafta) in human airway epithelial cells is underestimated due to the presence of ivacaftor.

Trikafta, currently the leading therapeutic in cystic fibrosis (CF), has demonstrated a real clinical benefit. This treatment is the triple combination therapy of two folding correctors elexacaftor/tezacaftor (VX445/VX661) plus the gating potentiator ivacaftor (VX770). In this study, our aim was to compare the properties of F508del-CFTR in cells treated with either lumacaftor (VX809), tezacaftor, elexacaftor, elexacaftor/tezacaftor with or without ivacaftor.

Absolute Quantification of Drug Vector Delivery to the Cytosol.

Macromolecular drugs inefficiently cross membranes to reach their cytosolic targets. They require drug delivery vectors to facilitate their translocation across the plasma membrane or escape from endosomes. Optimization of these vectors has however been hindered by the difficulty to accurately measure cytosolic arrival.

Shiga Toxin Uptake and Sequestration in Extracellular Vesicles Is Mediated by Its B-Subunit.

Shiga toxin (Stx)-stimulated blood cells shed extracellular vesicles (EVs) which can transfer the toxin to the kidneys and lead to hemolytic uremic syndrome. The toxin can be taken up by renal cells within EVs wherein the toxin is released, ultimately leading to cell death. The mechanism by which Stx is taken up, translocated, and sequestered in EVs was addressed in this study utilizing the B-subunit that binds to the globotriaosylceramide (Gb3) receptor.

Glycosylation and raft endocytosis in cancer.

Changes in glycosylation on proteins or lipids are one of the hallmarks of tumorigenesis. In many cases, it is still not understood how glycan information is translated into biological function. In this review, we discuss at the example of specific cancer-related glycoproteins how their endocytic uptake into eukaryotic cells is tuned by carbohydrate modifications.

Functional and Pharmacological Characterization of the Rare CFTR Mutation W361R.

Understanding the functional consequence of rare cystic fibrosis (CF) mutations is mandatory for the adoption of precision therapeutic approaches for CF. Here we studied the effect of the very rare CF mutation, W361R, on CFTR processing and function. We applied western blot, patch clamp and pharmacological modulators of CFTR to study the maturation and ion transport properties of pEGFP-WT and mutant CFTR constructs, W361R, F508del and L69H-CFTR, expressed in HEK293 cells.

Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity.

Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinatorial therapies highlights the necessity of identifying a broad panel of specific binding mode modulators, occupying several distinct binding sites at structural level. Here, we identified two small molecules, SBC040 and SBC219, which are two efficient cAMP-independent potentiators, acting at low concentration of forskolin with EC close to 1 μM and in a synergic way with the drug VX-770 on several CFTR mutants of classes II and III.

A Quality Improvement Initiative to Decrease Platelet Ordering Errors and a Proposed Model for Evaluating Clinical Decision Support Effectiveness.

Background And Objectives: Clinical decision support (CDS) and computerized provider order entry have been shown to improve health care quality and safety, but may also generate previously unanticipated errors. We identified multiple CDS tools for platelet transfusion orders. In this study, we sought to evaluate and improve the effectiveness of those CDS tools while creating and testing a framework for future evaluation of other CDS tools.

An underestimated sexually transmitted infection: amoebiasis.

is a cosmopolitan pathogenic parasite. It is spread via the feco-oral route and, to a lesser extent, via sexual intercourse. We report a case of hepatic and intestinal amoebiasis in a 67-year-old man who had never travelled to an endemic area.

2nd PSL Chemical Biology Symposium (2019): At the Crossroads of Chemistry and Biology.

Chemical Biology is the science of designing chemical tools to dissect and manipulate biology at different scales. It provides the fertile ground from which to address important problems of our society, such as human health and environment.

Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia.

Bicarbonate facilitates mucin unpacking and bacterial killing; however, its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through the cystic fibrosis (CF) transmembrane conductance regulator (CFTR; ABCC7) anion channel, and this is defective in CF. The anion exchanger pendrin (SLC26A4) also mediates HCO efflux and is upregulated by proinflammatory cytokines.