Obesity Pillars roundtable: Excessive weight reduction with highly effective anti-obesity medications (heAOMs).

Background: Historically, many anti-obesity medications (AOMs) were withdrawn from development and/or the market due to safety concerns. Another challenge was that, with some exceptions, most of these AOMs had limited weight reducing efficacy. Approved AOMs often did not meet the weight reduction expectations of either clinicians, or their patients.

Corrigendum to "Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022" [Obes Pillars 2 (2022) 100018].

[This corrects the article DOI: 10.1016/j.obpill.

Formation of styrene maleic acid lipid nanoparticles (SMALPs) using SMA thin film on a substrate.

Despite the important role of membrane proteins in biological function and physiology, studying them remains challenging because of limited biomimetic systems for the protein to remain in its native membrane environment. Cryo electron microscopy (Cryo-EM) is emerging as a powerful tool for analyzing the structure of membrane proteins. However, Cryo-EM and other membrane protein analyses are better studied in a native lipid bilayer.

Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This "Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association Clinical Practice Statement 2022" is intended to provide clinicians an overview of Food and Drug Administration (FDA) approved anti-obesity medications and investigational anti-obesity agents in development.

Methods: The scientific information for this Clinical Practice Statement (CPS) is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.

Results: This CPS describes pharmacokinetic principles applicable to those with obesity, and discusses the efficacy and safety of anti-obesity medications [e.

Nutrition and physical activity: An Obesity Medicine Association (OMA) Clinical Practice Statement 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on Nutrition and Physical Activity provides clinicians an overview of nutrition and physical activity principles applicable to the care of patients with increased body fat, especially those with adverse fat mass and adiposopathic metabolic consequences.

Methods: The scientific information and clinical guidance is based upon referenced evidence and derived from the clinical perspectives of the authors.

Results: This OMA CPS on Nutrition and Physical Activity provides basic clinical information regarding carbohydrates, proteins, fats (including trans fats, saturated fats, polyunsaturated fats, and monounsaturated fats), general principles of healthful nutrition, nutritional factors associated with improved health outcomes, and food labels.

Obesity history, physical exam, laboratory, body composition, and energy expenditure: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on History, Physical Exam, Body Composition and Energy Expenditure is intended to provide clinicians an overview of the clinical and diagnostic evaluation of patients with pre-obesity/obesity.

Methods: The scientific information for this CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.

Results: This CPS outlines important components of medical, dietary, and physical activity history as well as physical exams, with a focus on specific aspects unique to managing patients with pre-obesity or obesity.

Two-distinct polymer ubiquitin conjugates by photochemical grafting-from.

Protein-polymer bioconjugates present a way to make enzymes more efficient and robust for industrial and medicinal applications. While much work has focused on mono-functional conjugates, i.e.

Mapping protein-polymer conformations in bioconjugates with atomic precision.

Rational design of protein-polymer bioconjugates is hindered by limited experimental data and mechanistic understanding on interactions between the two. In this communication, nuclear magnetic resonance (NMR) paramagnetic relaxation enhancement (PRE) reports on distances between paramagnetic spin labels and NMR active nuclei, informing on the conformation of conjugated polymers. H/N-heteronuclear single quantum coherence (HSQC) NMR spectra were collected for ubiquitin (Ub) modified with block copolymers incorporating spin labels at different positions along their backbone.

Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells.

Background: Syndecans regulate cell migration thus having key roles in scarring and wound healing processes. Our previous results have shown that Thy-1/CD90 can engage both αvβ3 integrin and Syndecan-4 expressed on the surface of astrocytes to induce cell migration. Despite a well-described role of Syndecan-4 during cell movement, information is scarce regarding specific Syndecan-4 partners involved in Thy-1/CD90-stimulated cell migration.

Simple Derivatization of RAFT-Synthesized Styrene-Maleic Anhydride Copolymers for Lipid Disk Formulations.

Styrene-maleic acid copolymers have received significant attention because of their ability to interact with lipid bilayers and form styrene-maleic acid copolymer lipid nanoparticles (SMALPs). However, these SMALPs are limited in their chemical diversity, with only phenyl and carboxylic acid functional groups, resulting in limitations because of sensitivity to low pH and high concentrations of divalent metals. To address this limitation, various nucleophiles were reacted with the anhydride unit of well-defined styrene-maleic anhydride copolymers in order to assess the potential for a new lipid disk nanoparticle-forming species.

The role of endothelial MERTK during the inflammatory response in lungs.

As a key homeostasis regulator in mammals, the MERTK receptor tyrosine kinase is crucial for efferocytosis, a process that requires remodeling of the cell membrane and adjacent actin cytoskeleton. Membrane and cytoskeletal reorganization also occur in endothelial cells during inflammation, particularly during neutrophil transendothelial migration (TEM) and during changes in permeability. However, MERTK's function in endothelial cells remains unclear.

Vinculin and metavinculin exhibit distinct effects on focal adhesion properties, cell migration, and mechanotransduction.

Vinculin (Vcn) is a ubiquitously expressed cytoskeletal protein that links transmembrane receptors to actin filaments, and plays a key role in regulating cell adhesion, motility, and force transmission. Metavinculin (MVcn) is a Vcn splice isoform that contains an additional exon encoding a 68-residue insert within the actin binding tail domain. MVcn is selectively expressed at sub-stoichiometic amounts relative to Vcn in smooth and cardiac muscle cells.

Software for lattice light-sheet imaging of FRET biosensors, illustrated with a new Rap1 biosensor.

Lattice light-sheet microscopy (LLSM) is valuable for its combination of reduced photobleaching and outstanding spatiotemporal resolution in 3D. Using LLSM to image biosensors in living cells could provide unprecedented visualization of rapid, localized changes in protein conformation or posttranslational modification. However, computational manipulations required for biosensor imaging with LLSM are challenging for many software packages.

Mechanotransduction: from the cell surface to the nucleus via RhoA.

Cells respond and adapt to their physical environments and to the mechanical forces that they experience. The translation of physical forces into biochemical signalling pathways is known as mechanotransduction. In this review, we focus on two aspects of mechanotransduction.

Structural characterization of styrene-maleic acid copolymer-lipid nanoparticles (SMALPs) using EPR spectroscopy.

Spectroscopic studies of membrane proteins (MPs) are challenging due to difficulties in preparing homogenous and functional lipid membrane mimetic systems into which membrane proteins can properly fold and function. It has recently been shown that styrene-maleic acid (SMA) copolymers act as a macromolecular surfactant and therefore facilitate the formation of disk-shaped lipid bilayer nanoparticles (styrene-maleic acid copolymer-lipid nanoparticles (SMALPs)) that retain structural characteristics of native lipid membranes. We have previously reported controlled synthesis of SMA block copolymers using reversible addition-fragmentation chain transfer (RAFT) polymerization, and that alteration of the weight ratio of styrene to maleic acid affects nanoparticle size.

Talin: a protein designed for mechanotransduction.

Mechanotransduction, the topic of this volume, has become a major area of cell biological research. That cells respond to their external environments has been known for decades; however, research was largely confined to studying how cells respond to soluble factors and not mechanical forces. Here, I will use talin, a canonical mechanosensitive protein, to illustrate certain emerging concepts.

Characterizing the structure of styrene-maleic acid copolymer-lipid nanoparticles (SMALPs) using RAFT polymerization for membrane protein spectroscopic studies.

Membrane proteins play an important role in maintaining the structure and physiology of an organism. Despite their significance, spectroscopic studies involving membrane proteins remain challenging due to the difficulties in mimicking their native lipid bilayer environment. Membrane mimetic systems such as detergent micelles, liposomes, bicelles, nanodiscs, lipodisqs have improved the solubility and folding properties of the membrane proteins for structural studies, however, each mimetic system suffers from its own limitations.

Cell-Cycle-Dependent Regulation of Cell Adhesions: Adhering to the Schedule: Three papers reveal unexpected properties of adhesion structures as cells progress through the cell cycle.

Focal adhesions disassemble during mitosis, but surprisingly little is known about how these structures respond to other phases of the cell cycle. Three recent papers reveal unexpected results as they examine adhesions through the cell cycle. A biphasic response is detected where focal adhesions grow during S phase before disassembly begins early in G2.

Small GTPase Rap1A/B Is Required for Lymphatic Development and Adrenomedullin-Induced Stabilization of Lymphatic Endothelial Junctions.

Objective- Maintenance of lymphatic permeability is essential for normal lymphatic function during adulthood, but the precise signaling pathways that control lymphatic junctions during development are not fully elucidated. The G-coupled AM (adrenomedullin) signaling pathway is required for embryonic lymphangiogenesis and the maintenance of lymphatic junctions during adulthood. Thus, we sought to elucidate the downstream effectors mediating junctional stabilization in lymphatic endothelial cells.

A Rnd3/p190RhoGAP pathway regulates RhoA activity in idiopathic pulmonary fibrosis fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is an incurable disease of the lung that is characterized by excessive deposition of extracellular matrix (ECM), resulting in disruption of normal lung function. The signals regulating fibrosis include both transforming growth factor beta (TGF-β) and tissue rigidity and a major signaling pathway implicated in fibrosis involves activation of the GTPase RhoA. During studies exploring how elevated RhoA activity is sustained in IPF, we discovered that not only is RhoA activated by profibrotic stimuli but also that the expression of Rnd3, a major antagonist of RhoA activity, and the activity of p190RhoGAP (p190), a Rnd3 effector, are both suppressed in IPF fibroblasts.

Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction.

The nucleus has long been postulated to play a critical physical role during cell polarization and migration, but that role has not been defined or rigorously tested. Here, we enucleated cells to test the physical necessity of the nucleus during cell polarization and directed migration. Using enucleated mammalian cells (cytoplasts), we found that polarity establishment and cell migration in one dimension (1D) and two dimensions (2D) occur without the nucleus.

LARG GEF and ARHGAP18 orchestrate RhoA activity to control mesenchymal stem cell lineage.

The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure.

Polymer Conjugation to Enhance Cellulase Activity and Preserve Thermal and Functional Stability.

A thermophilic cellulase, FnCel5a, from Fervidobacterium nodosum was conjugated with various functional polymers including cationic, anionic, and strongly and weakly hydrogen bonding polymers. The activity of FnCel5a toward a high-molecular-weight carboxymethyl cellulose substrate was enhanced by polymer conjugation. Activity enhancements of 50% or greater observed for acrylamide and mixed N,N-dimethyl acrylamide-2-(N,N-dimethylamino)ethyl methacrylate polymers, suggesting that the greatest enhancements were caused by polymers capable of noncovalent interactions with the substrate.