The Membrane Phase Transition Gives Rise to Responsive Plasma Membrane Structure and Function.

Several groups have recently reported evidence for the emergence of domains in cell plasma membranes when membrane proteins are organized by ligand binding or assembly of membrane proximal scaffolds. These domains recruit and retain components that favor the liquid-ordered phase, adding to a decades-old literature interrogating the contribution of membrane phase separation in plasma membrane organization and function. Here we propose that both past and present observations are consistent with a model in which membranes have a high compositional susceptibility, arising from their thermodynamic state in a single phase that is close to a miscibility phase transition.

Cardioprotective properties of quercetin in fescue toxicosis-induced cardiotoxicity via heart-gut axis in lambs (Ovis Aries).

The present study investigated whether quercetin mitigated fescue toxicosis-induced cardiovascular injury via the heart-gut axis. Twenty-four commercial Dorper lambs were stratified by body weight and assigned randomly to diets in one of four groups: endophyte-free without quercetin (E-,Q-), endophyte-positive without quercetin (E+,Q-), endophyte-positive plus 4 g/kg quercetin (E+,Q+) or endophyte-free plus 4 g/kg quercetin (E-,Q+) for 42 days. Body weight and average daily feed intake (ADFI) of lambs fed the endophyte-positive diets showed significant decreases.

Measuring the Co-Localization and Dynamics of Mobile Proteins in Live Cells Undergoing Signaling Responses.

Single molecule imaging in live cells enables the study of protein interactions and dynamics as they participate in signaling processes. When combined with fluorophores that stochastically transition between fluorescent and reversible dark states, as in super-resolution localization imaging, labeled molecules can be visualized in single cells over time. This improvement in sampling enables the study of extended cellular responses at the resolution of single molecule localization.

Membrane phase separation drives responsive assembly of receptor signaling domains.

Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on phase separation alone fall short of describing the rich organization available within cell membranes. Here we present comprehensive experimental evidence motivating an updated model of plasma membrane heterogeneity in which membrane domains assemble in response to protein scaffolds. Quantitative super-resolution nanoscopy measurements in live B lymphocytes detect membrane domains that emerge upon clustering B cell receptors (BCRs).

The plasma membrane as an adaptable fluid mosaic.

The fluid mosaic model proposed by Singer and Nicolson established a powerful framework to interrogate biological membranes that has stood the test of time. They proposed that the membrane is a simple fluid, meaning that proteins and lipids are randomly distributed over distances larger than those dictated by direct interactions. Here we present an update to this model that describes a spatially adaptable fluid membrane capable of tuning local composition in response to forces originating outside the membrane plane.

Effects of two dietary crude protein levels on finishing performance, meat quality, and gene expression of market lambs.

Seventeen crossbred lambs were assigned randomly to low-protein (LP; 8% crude protein [CP]; n = 9) and high-protein (HP; 13% CP; n = 8) diets for 9 weeks. The final body weight, average daily feed intake (ADFI), and average daily gain (ADG) of the HP lambs were significantly higher (P < 0.05) than the LP lambs; however, gain to feed ratio (G:F) for the LP lambs was significantly higher (P < 0.

Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function.

Chimeric antigen receptor (CAR)-modified T cell therapy is effective in treating lymphomas, leukemias, and multiple myeloma in which the tumor cells express high amounts of target antigen. However, achieving durable remission for these hematological malignancies and extending CAR T cell therapy to patients with solid tumors will require receptors that can recognize and eliminate tumor cells with a low density of target antigen. Although CARs were designed to mimic T cell receptor (TCR) signaling, TCRs are at least 100-fold more sensitive to antigen.

Comparison of Growth Performance and Meat Quality Traits of Commercial Cross-Bred Pigs versus the Large Black Pig Breed.

The meat quality of different pig breeds is associated with their different muscle tissue physiological processes, which involves a large variety of genes related with muscle fat and energy metabolism. Understanding the differences of biological processes of muscle after slaughter is helpful to reveal the meat quality development of different breeds. Therefore, eight native Large Black pigs (BP), with high fat content in meat, and seven cross-bred commercial pigs (CP), which had a high feed efficiency with high lean meat, were used to investigate the differences in their meat quality and RNA transcriptomes.

SMAUG: Analyzing single-molecule tracks with nonparametric Bayesian statistics.

Single-molecule fluorescence microscopy probes nanoscale, subcellular biology in real time. Existing methods for analyzing single-particle tracking data provide dynamical information, but can suffer from supervisory biases and high uncertainties. Here, we develop a method for the case of multiple interconverting species undergoing free diffusion and introduce a new approach to analyzing single-molecule trajectories: the Single-Molecule Analysis by Unsupervised Gibbs sampling (SMAUG) algorithm, which uses nonparametric Bayesian statistics to uncover the whole range of information contained within a single-particle trajectory dataset.

Effects of eicosapentaenoic acid and docosahexaenoic acid on C2C12 cell adipogenesis and inhibition of myotube formation.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulate cellular metabolic functions and gene expression. This study investigated the impacts of EPA and DHA on gene expression and morphological changes during adipogenic inducement in C2C12 myoblasts. Cells were cultured and treated with differentiation medium with and without 50 μM EPA and DHA.

Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane.

Lipids and the membranes they form are fundamental building blocks of cellular life, and their geometry and chemical properties distinguish membranes from other cellular environments. Collective processes occurring within membranes strongly impact cellular behavior and biochemistry, and understanding these processes presents unique challenges due to the often complex and myriad interactions between membrane components. Super-resolution microscopy offers a significant gain in resolution over traditional optical microscopy, enabling the localization of individual molecules even in densely labeled samples and in cellular and tissue environments.

Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.

Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain.

Functional nanoscale coupling of Lyn kinase with IgE-FcεRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling.

The allergic response is initiated on the plasma membrane of mast cells by phosphorylation of the receptor for immunoglobulin E (IgE), FcεRI, by Lyn kinase after IgE-FcεRI complexes are cross-linked by multivalent antigen. Signal transduction requires reorganization of receptors and membrane signaling proteins, but this spatial regulation is not well defined. We used fluorescence localization microscopy (FLM) and pair-correlation analysis to measure the codistribution of IgE-FcεRI and Lyn on the plasma membrane of fixed cells with 20- to 25-nm resolution.

Rab11 Regulates the Mast Cell Exocytic Response.

Stimulated exocytic events provide a means for physiological communication and are a hallmark of the mast cell-mediated allergic response. In mast cells these processes are triggered by antigen crosslinking of IgE bound to its high-affinity receptor, FcϵRI, on the cell surface. Here we use the endosomal v-SNARE VAMP8, and the lysosomal hydrolase β-hexosaminidase (β-Hex), each C-terminally fused to super-ecliptic pHluorin, to monitor stimulated exocytosis.

Bariatric surgery: a viable treatment option for patients with severe mental illness.

Background: Although bariatric surgery has become a recognized treatment for obesity, its utility among patients with severe psychiatric disorders has not been extensively studied. A few studies have reported similar weight loss outcomes in these patients, but psychiatric status after bariatric surgery has been studied only minimally, and it is unknown if exacerbation of the mental illness affects weight loss.

Objectives: The aim of this study was to shed greater light on the issue of serious mental illness and bariatric surgery.

Distinct stages of stimulated FcεRI receptor clustering and immobilization are identified through superresolution imaging.

Recent advances in fluorescence localization microscopy have made it possible to image chemically fixed and living cells at 20 nm lateral resolution. We apply this methodology to simultaneously record receptor organization and dynamics on the ventral surface of live RBL-2H3 mast cells undergoing antigen-mediated signaling. Cross-linking of IgE bound to FcεRI by multivalent antigen initiates mast cell activation, which leads to inflammatory responses physiologically.

Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting.

We present an analytical method using correlation functions to quantify clustering in super-resolution fluorescence localization images and electron microscopy images of static surfaces in two dimensions. We use this method to quantify how over-counting of labeled molecules contributes to apparent self-clustering and to calculate the effective lateral resolution of an image. This treatment applies to distributions of proteins and lipids in cell membranes, where there is significant interest in using electron microscopy and super-resolution fluorescence localization techniques to probe membrane heterogeneity.

Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers.

The design and synthesis of protein-like polymers is a fundamental challenge in materials science. A biomimetic approach is to explore the impact of monomer sequence on non-natural polymer structure and function. We present the aqueous self-assembly of two peptoid polymers into extremely thin two-dimensional (2D) crystalline sheets directed by periodic amphiphilicity, electrostatic recognition and aromatic interactions.

Pain, coping and health care utilization in younger and older adults with sickle cell disease.

Sickle cell disease is characterized by acute pain crises. Pain, chronic medical problems, utilization and coping were compared in younger vs older patients using questionnaires and medical record review. Groups reported similar pain intensity and medical conditions.

A nanocube plasmonic sensor for molecular binding on membrane surfaces.

Detection and characterization of molecular interactions on membrane surfaces is important to biological and pharmacological research. Here, silver nanocubes interfaced with glass-supported model membranes form a label-free sensor that measures protein binding to the membrane. The technique utilizes plasmon resonance scattering of nanocubes, which are chemically coupled to the membrane.