Surviving on a Rock, but for How Long? Deviations in the Thermoregulatory Strategy of the Milos Wall Lizard ().

Reptiles are unable to generate metabolic heat and regulate body temperature behaviorally depending on environmental conditions. The thermal quality of their habitat is therefore of pivotal importance for their survival. Lizards render themselves as ideal ectothermic models, and their thermal biology has been extensively studied.

Development of the "LAser Surgical skills Evaluation for Residents" (LASER) Scale Through a Modified Delphi Method.

Background: The CO laser is frequently used during microlaryngeal surgery (MLS) for a variety of pathology including laryngeal malignancy and stenosis. Learning how to use the laser safely is part of the curriculum for every otolaryngology resident. However, assessment of laryngoscopy technical skills can be challenging for supervisors, making it difficult to adequately provide feedback to trainees.

Positive allosteric modulation of a GPCR ternary complex.

The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterized by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and the efficacy of orthosteric agonists. The influence allosteric modulators have on the high-affinity active state of the GPCR-G protein ternary complex is unknown due to limitations on attempting to characterize this interaction in recombinant whole cell or membrane-based assays.

Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs.

Class B1 G protein-coupled receptors (GPCRs) are peptide hormone receptors and well validated therapeutic targets, however development of non-peptide drugs targeting this class of receptors is challenging. Recently, a series of isoquinoline-based derivates were reported in the patent literature as allosteric ligands for the glucagon receptor subfamily, and two compounds, LSN3451217 and LSN3556672, were used to facilitate structural studies with the glucagon-like peptide-1 receptor (GLP-1R) and glucose dependent insulinotropic peptide receptor (GIPR) bound to orthosteric agonists. Here we pharmacologically characterized stereoisomers of LSN3451217 and LSN3556672, across the class B1 GPCR family.

Cholesterol-dependent dynamic changes in the conformation of the type 1 cholecystokinin receptor affect ligand binding and G protein coupling.

Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding and reducing calcium signaling, while agonist actions of the closely related CCK2R are not. In this work, we identified a set of chimeric human CCK1R/CCK2R mutations that exchange the cholesterol sensitivity of these 2 receptors, providing powerful tools when expressed in CHO and HEK-293 model cell lines to explore mechanisms.

Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges.

Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors (GPCRs) that are activated by the endogenous neurotransmitter, acetylcholine (ACh). Disruption of mAChR signalling has been associated with a variety of neurological disorders and non-neurological diseases. Consequently, the development of agonists and antagonists of the mAChRs has been a major avenue in drug discovery.

Discovery of 2-Methyl-5-(1-pyrazol-4-yl)pyridines and Related Heterocycles as Promising M mAChR Positive Allosteric Modulators for the Treatment of Neurocognitive Disorders.

The M muscarinic acetylcholine receptor (mAChR) is a biological target for neurocognitive disorders. Compound is an -PAM for the M mAChR. Herein, we report the design, synthesis, and evaluation of novel putative M mAChR PAMs based on .

The inability to mourn: Past and current challenges for psychoanalysis.

Although the capacity to mourn is ubiquitously acknowledged as critical for individual psychic functioning, the impact of this capacity on a collective social level has been examined to a very limited extent in the psychoanalytic literature to date. The two papers that take up this this topic thus bring various critical and complex issues to our attention. After reviewing and commenting on these papers, I discuss how these issues are particularly relevant today to society in general and psychoanalysis in particular.

Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice.

Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development.

Impact of secretin receptor homo-dimerization on natural ligand binding.

Class B G protein-coupled receptors can form dimeric complexes important for high potency biological effects. Here, we apply pharmacological, biochemical, and biophysical techniques to cells and membranes expressing the prototypic secretin receptor (SecR) to gain insights into secretin binding to homo-dimeric and monomeric SecR. Spatial proximity between peptide and receptor residues, probed by disulfide bond formation, demonstrates that the secretin N-terminus moves from adjacent to extracellular loop 3 (ECL3) at wild type SecR toward ECL2 in non-dimerizing mutants.

The use of artificial intelligence in reconstructive surgery for head and neck cancer: a systematic review.

Objectives: The popularity of artificial intelligence (AI) in head and neck cancer (HNC) management is increasing, but postoperative complications remain prevalent and are the main factor that impact prognosis after surgery. Hence, recent studies aim to assess new AI models to evaluate their ability to predict free flap complications more effectively than traditional algorithms. This systematic review aims to summarize current evidence on the utilization of AI models to predict complications following reconstructive surgery for HNC.

Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.

Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor exists, the amylin (Amy) 1 receptor (AMYR), yet its involvement in the pathology of migraine is poorly understood. AMYR and CGRPR are heterodimers consisting of receptor activity-modifying protein 1 (RAMP1) with the calcitonin receptor (CTR) and the calcitonin receptor-like receptor (CLR), respectively.

Spatiotemporal Patterns of Reptile and Amphibian Road Fatalities in a Natura 2000 Area: A 12-Year Monitoring of the Lake Karla Mediterranean Wetland.

The pervasive expansion of human-engineered infrastructure, particularly roads, has fundamentally reshaped landscapes, profoundly affecting wildlife interactions. Wildlife-vehicle collisions, a common consequence of this intricate interplay, frequently result in fatalities, extending their detrimental impact within Protected Areas (PAs). Among the faunal groups most susceptible to road mortality, reptiles and amphibians stand at the forefront, highlighting the urgent need for global comprehensive mitigation strategies.

Ligand-directed biased agonism at human histamine H receptor isoforms across Gα- and β-arrestin2-mediated pathways.

The histamine H receptor (HR) is a neurotransmitter receptor that is primarily found in the brain, where it controls the release and synthesis of histamine, as well as the release of other neurotransmitters (e.g. dopamine, serotonin).

Predictors of prolonged treatment time intervals in oral cavity cancer.

Objectives: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals.

Material And Methods: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy.

Patterns of alaryngeal voice adoption and predictive factors of vocal rehabilitation failure following total laryngectomy.

Objective: We aimed to determine patterns of alaryngeal voice acquisition and predictive factors of vocal rehabilitation (VR) failure following total laryngectomy (TL) at a large Canadian tertiary care center.

Methods: All consecutive patients having undergone a TL between January 1st, 2011 and December 31st, 2019, at the Centre Hospitalier de l'Université de Montréal were included.

Results: One hundred and ninety-seven laryngectomized patients were identified.

Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer.

Importance: Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada.

Objective: To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival.