Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by erm(41) in Mycobacterium abscessus.

Background: Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections, particularly in individuals with underlying conditions, such as cystic fibrosis or chronic obstructive pulmonary disease. Macrolides, such as clarithromycin (CLR) or azithromycin (AZM), represent the cornerstone of antibiotherapy against the M. abscessus species.

Membrane mechanics dictate axonal pearls-on-a-string morphology and function.

Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string.

Unravelling impacts of the insecticide deltamethrin on neuronal sodium channels in honey bees: Molecular insights and behavioural outcomes.

The current risk assessment framework for insecticides suffers from certain shortcomings in adequately addressing the effects of low doses on off-target species. To remedy this gap, a combination of behavioural assays and in vitro cellular approaches are required to refine the precision of toxicity assessment. The domestic honey bee has long been standing as an emblematic pollinator in ecotoxicology, and once more, it provides us with a practical testing model for this purpose.

Selective binding and removal of copper from biological fluids-why are PSP ligands so efficient?

The following comment tries to answer why the reported removal of copper from buffer, cell culture medium, and cell extract by a supported chelator called phenPS is so selective and efficient. It is further argued that the family of PSP (phosphine sulfide-stabilized phosphines) chelators, due to their unique properties, have various potential future application in biology and medicine such as chelation therapy, copper-sensors, or tools to understand copper metabolism.

ERBB2 Comprehensive Profiling and Prognostication in Stage III Colon Cancer: Findings From PETACC8 and IDEA-France Cohorts.

Background & Aims: ERBB2 pathway activation, through amplification or activating mutations, represents a new target for colon cancer (CC) treatment. Molecular methods were compared with the gold standard for assessing ERBB2 status, and the prognostic value of ERBB2 amplification, mutations, and expression was determined using data from 2 phase 3 trials involving nearly 3000 patients with stage III CC.

Methods: In the PETACC8 trial, immunohistochemistry and fluorescence in situ hybridization, DNA, and RNA analysis were performed on 1813, 1719, and 1733 samples, respectively.

Fluopyram SDHI pesticide alters fish physiology and behaviour despite low in vitro effects on mitochondria.

Pollution from pesticides is an increasing concern for human health and biodiversity conservation. However, there is lack of knowledge about some emerging molecules such as SDHI fungicides (succinate dehydrogenase inhibitors) that are widely used but potentially highly toxic for vertebrates. Boscalid, fluopyram, and bixafen are 3 frequent SDHI molecules commonly detected in surface waters, which may pose risks to aquatic species.

Facilitators and challenges in collaboration between public health units and faith-based organizations to promote COVID-19 vaccine confidence in Ontario.

Background: Equitable access to vaccination remains a concern, particularly among population groups made structurally vulnerable. These population groups reflect the diversity of communities that are confronted with structural barriers caused by systemic racism and oppression and result in them experiencing suffer disadvantage and discrimination based on citizenship, race, ethnicity, ancestry, religion, spiritual beliefs, and/or gender identity. In Canada, Ontario public health units (PHUs) engage with faith-based organizations (FBOs) to improve vaccine confidence among populations made structurally vulnerable.

Variability of functional and biodiversity responses to perturbations is predictable and informative.

Perturbations such as climate change, invasive species and pollution, impact the functioning and diversity of ecosystems. However diversity has many meanings, and ecosystems provide a plethora of functions. Thus, on top of the various perturbations that global change represents, there are also many ways to measure a perturbation's ecological impact.

Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors.

Background: Lung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients' outcome.

Methods: We applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages.

Remodelling of Rea1 linker domain drives the removal of assembly factors from pre-ribosomal particles.

The ribosome maturation factor Rea1 (or Midasin) catalyses the removal of assembly factors from large ribosomal subunit precursors and promotes their export from the nucleus to the cytosol. Rea1 consists of nearly 5000 amino-acid residues and belongs to the AAA+ protein family. It consists of a ring of six AAA+ domains from which the ≈1700 amino-acid residue linker emerges that is subdivided into stem, middle and top domains.

Insulin-degrading enzyme regulates insulin-directed cellular autoimmunity in murine type 1 diabetes.

Type 1 diabetes results from the destruction of pancreatic beta cells by autoreactive T cells. As an autoantigen with extremely high expression in beta cells, insulin triggers and sustains the autoimmune CD4 and CD8 T cell responses and islet inflammation. We have previously shown that deficiency for insulin-degrading enzyme (IDE), a ubiquitous cytosolic protease with very high affinity for insulin, induces endoplasmic reticulum (ER) stress and proliferation in islet cells and protects non-obese diabetic mice (NOD) from diabetes.

Prenatal Acoustic Signals Influence Nestling Heat Shock Protein Response to Heat and Heterophil-to-Lymphocyte Ratio in a Desert Bird.

Heat shock proteins (HSPs) are essential to cellular protection against heat stress. However, the causes of inter-individual variation in HSP regulation remain unclear. This study aimed to test the impact of early-life conditions on the HSP response to heat in zebra finches.

Deciphering Folate Receptor alphaGene Expression and mRNA Signatures in Ovarian Cancer: Implications for Precision Therapies.

Antibody-drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC.

Modulating the Iron Microenvironment for a Cooperative Interplay Between Fe-N-C Single Atoms and FeC Nanoclusters on the Oxygen Reduction Reaction.

The coexistence of single atoms and nanoparticles is shown to increase the oxygen reduction performance in Fe-N-C electrocatalysts, but the mechanisms underlying this synergistic effect remain elusive. In this study, model Fe-N-C electrocatalysts with controlled ratios of FeN sites and FeC nanoclusters is systematically designed and synthesized. Experiments and density functional theory (DFT) computations reveal that FeC nanoclusters near FeN sites modulate the electron density of the Fe single-atom microenvironment through an electron withdrawing effect.

The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.

Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of the viral genomes within the nucleus. A key pattern involves quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML NBs) forming viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated that these viral genomes are chromatinized with the H3.

Liquid Biopsy versus CT: Comparison of Tumor Burden Quantification in 1065 Patients with Metastases.

Background Tumor fraction (TF) at liquid biopsy is a potential noninvasive marker for tumor burden, but validation is needed. Purpose To evaluate TF as a potential surrogate for tumor burden, assessed at contrast-enhanced CT across diverse metastatic cancers. Methods This retrospective monocentric study included patients with cancer and metastatic disease, with TF results and contemporaneous contrast-enhanced CT performed between January 2021 and January 2023.