Bayesian modeling of HFC production pipeline suggests growth in unreported CFC by-product and feedstock production.

Observationally-derived emissions of ozone depleting substances must be scrutinized to maintain the progress made by the Montreal Protocol in protecting the stratospheric ozone layer. Recent observations of three chlorofluorocarbons (CFCs), CFC-113, CFC-114, and CFC-115, suggest that emissions of these compounds have not decreased as expected given global reporting of their production. These emissions have been associated with hydrofluorocarbon (HFC) production, which can require CFCs as feedstocks or generate CFCs as by-products, yet emissions from these pathways have not been rigorously quantified.

Effects of topical 0.5% tropicamide and 1% atropine on pupil diameter, intraocular pressure, and tear production, in healthy pet rabbits.

Objective: To evaluate the effects of topical application of 0.5% tropicamide and 1% atropine on pupil diameter (PD), intraocular pressure (IOP), and tear production (TP) in healthy pet rabbits.

Animals Studied: Ten healthy client-owned rabbits.

What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants.

The study of the adverse effects of chemical substances on living organisms is an old and intense field of research. However, toxicological and environmental health sciences have long been dominated by descriptive approaches that enable associations or correlations but relatively few robust causal links and molecular mechanisms. Recent achievements have shown that structural biology approaches can bring this added value to the field.

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen.

is the most prevalent bacterial sexually transmitted pathogen worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and de-centralized production of recombinant protein vaccine antigens.

Ventricular Access Utilizing Cutaneous Reference Points: Statistical Analysis and Proposal of a New Ventricular Entry Point.

Objectives: Perform radiologic measurements and analysis of normal brain computed tomography (CT) scans; delineate a new ventricular entry point from cutaneous landmarks, highlighting the potential surgical implications of these findings.

Methods: Six radiologic distances (AR; BR; AL; BL, C, and D) were measured in normal brain CT scans using Horos software. Statistical analysis of the measurements was performed with minitab18 software based on age, sex, and side.

Corrigendum: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project.

[This corrects the article DOI: 10.3389/ftox.2023.

Nutritional cataracts in a wolf litter treated by phacoemulsification.

Objective: To describe the clinical findings in a wolf litter with nutritional cataracts and determine the treatment outcomes after phacoemulsification.

Procedure: Bilateral nutritional cataracts were diagnosed in four hand-fed 10-week-old wolves (Canis lupus). The information collected included signalment, physical and ophthalmic examination findings, ocular ultrasonography and electroretinography results, and postoperative outcomes.

Evaluation of Inactivation Methods for Rift Valley Fever Virus in Mouse Microglia.

Rift Valley fever phlebovirus (RVFV) is a highly pathogenic mosquito-borne virus with bioweapon potential due to its ability to be spread by aerosol transmission. Neurological symptoms are among the worst outcomes of infection, and understanding of pathogenesis mechanisms within the brain is limited. RVFV is classified as an overlap select agent by the CDC and USDA; therefore, experiments involving fully virulent strains of virus are tightly regulated.

Structural Insights into the Activation of Human Aryl Hydrocarbon Receptor by the Environmental Contaminant Benzo[a]pyrene and Structurally Related Compounds.

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor belonging to the bHLH/PAS protein family and responding to hundreds of natural and chemical substances. It is primarily involved in the defense against chemical insults and bacterial infections or in the adaptive immune response, but also in the development of pathological conditions ranging from inflammatory to neoplastic disorders. Despite its prominent roles in many (patho)physiological processes, the lack of high-resolution structural data has precluded for thirty years an in-depth understanding of the structural mechanisms underlying ligand-binding specificity, promiscuity and activation of AHR.

Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project.

In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals.

2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors.

2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether 2,4-DTBP is a potential obesogen.

Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex.

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.

A novel nuclear receptor subfamily enlightens the origin of heterodimerization.

Background: Nuclear receptors are transcription factors of central importance in human biology and associated diseases. Much of the knowledge related to their major functions, such as ligand and DNA binding or dimerization, derives from functional studies undertaken in classical model animals. It has become evident, however, that a deeper understanding of these molecular functions requires uncovering how these characteristics originated and diversified during evolution, by looking at more species.

Design and in vitro characterization of RXR variants as tools to investigate the biological role of endogenous rexinoids.

Retinoid X receptors (RXRα, β, and γ) are essential members of the nuclear receptor (NR) superfamily of ligand-dependent transcriptional regulators that bind DNA response elements and control the expression of large gene networks. As obligate heterodimerization partners of many NRs, RXRs are involved in a variety of pathophysiological processes. However, despite this central role in NR signaling, there is still no consensus regarding the precise biological functions of RXRs and the putative role of the endogenous ligands (rexinoids) previously proposed for these receptors.

Large-scale application of free energy perturbation calculations for antibody design.

Alchemical free energy perturbation (FEP) is a rigorous and powerful technique to calculate the free energy difference between distinct chemical systems. Here we report our implementation of automated large-scale FEP calculations, using the Amber software package, to facilitate antibody design and evaluation. In combination with Hamiltonian replica exchange, our FEP simulations aim to predict the effect of mutations on both the binding affinity and the structural stability.

MAVS mediates a protective immune response in the brain to Rift Valley fever virus.

Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice.

Nest-site selection and its influence on breeding success in a poorly-known and declining seabird: The Tahiti petrel Pseudobulweria rostrata.

The Tahiti petrel (Pseudobulweria rostrata) is a rare and declining seabird whose breeding biology and nest-site selection are poorly known. Nest-site selection is critical to seabird population fitness, and understanding the factors driving it is essential for designing effective conservation measures. Here, we measured several variables (topographical, physical and environmental) to characterize Tahiti petrel nesting habitats and burrows (i.

Human Neuraminidases: Structures and Stereoselective Inhibitors.

This Perspective describes the classification, structures, substrates, mechanisms of action, and implications of human neuraminidases (hNEUs) in various pathologies. Some inhibitors have been developed for each isoform, leading to more precise interactions with hNEUs. Although crystal structure data are available for NEU2, most of the findings are based on NEU1 inhibition, and limited information is available for other hNEUs.

Structure-Based and Knowledge-Informed Design of B-Raf Inhibitors Devoid of Deleterious PXR Binding.

Dabrafenib is an anticancer drug currently used in the clinics, alone or in combination. However, dabrafenib was recently shown to potently activate the human nuclear receptor pregnane X receptor (PXR). PXR activation increases the clearance of various chemicals and drugs, including dabrafenib itself.

Interspecies Differences in Activation of Peroxisome Proliferator-Activated Receptor γ by Pharmaceutical and Environmental Chemicals.

Endocrine disrupting chemicals (EDCs) are able to deregulate the hormone system, notably through interactions with nuclear receptors (NRs). The mechanisms of action and biological effects of many EDCs have mainly been tested on human and mouse but other species such as zebrafish and xenopus are increasingly used as a model to study the effects of EDCs. Among NRs, peroxisome proliferator-activated receptor γ (PPARγ) is a main target of EDCs, for which most experimental data have been obtained from human and mouse models.

Functional analyses of phosphatidylserine/PI(4)P exchangers with diverse lipid species and membrane contexts reveal unanticipated rules on lipid transfer.

Background: Lipid species are accurately distributed in the eukaryotic cell so that organelle and plasma membranes have an adequate lipid composition to support numerous cellular functions. In the plasma membrane, a precise regulation of the level of lipids such as phosphatidylserine, PI(4)P, and PI(4,5)P, is critical for maintaining the signaling competence of the cell. Several lipid transfer proteins of the ORP/Osh family contribute to this fine-tuning by delivering PS, synthesized in the endoplasmic reticulum, to the plasma membrane in exchange for PI(4)P.

Development of potent and effective synthetic SARS-CoV-2 neutralizing nanobodies.

The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives of over 3.9 million people globally, at the time of this publication. Neutralizing humanized nanobody (VH)-based antibodies (VH-huFc) represent a promising therapeutic intervention strategy to address the current SARS-CoV-2 pandemic and provide a powerful toolkit to address future virus outbreaks.