Modular Photoswitchable Molecular Glues for Chemo-optogenetic Control of Protein Function in Living Cells.

Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological systems and to dissect complex biological regulatory networks. Here, we report a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs) that can undergo repeated cycles of optical control to switch protein function on and off. We use molecular dynamics (MD) simulations to rationally design the sMGs and further expand their scope by incorporating different photoswitches, resulting in sMGs with customizable properties.

Bio-Based Polyurethane Composites with Adjustable Fluorescence and Ultraviolet Shielding for Anti-Counterfeiting and Ultraviolet Protection.

Polyurethane and its composites play an important role in innovative packing materials including anticounterfeiting and ultraviolet protection, however, they are mainly derived from petroleum resources that are not sustainable. In this study, a 100% biobased thermoplastic polyurethane (Bio-TPU) was synthesized using biobased poly(trimethylene ether) glycol, pentamethylene disocyanate, and 1,4-butanediol. Subsequently, biobased tannic acid (TA) was employed to prepare biobased composites.

A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation.

The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging.

Distortion Effect on the UHPC Box Girder with Vertical Webs: Theoretical Analysis and Case Study.

Distortion deformation usually imposes a potential threat to bridge safety. In order to comprehensively understand the distortion effect on thin-walled ultra-high performance concrete (UHPC) box girders, an innovative approach encompassing the governing distortion differential equation is introduced in this study based on the general definition of distortion angle within the cross-section plane. The analytical results obtained from the proposed method are in accordance with those obtained from the energy method, and exhibit favorable agreement with experimental findings documented in the existing literature.

In-situ self-crosslinking strategy for super-tough polylactic acid/ bio-based polyurethane blends.

As a bio-based degradable plastic, polylactic acid (PLA) is highly commercialized, but its inherent brittleness limits its widespread use. In-situ polymerization techniques are effective in improving the toughness of PLA. However, the enhancement of the toughening effect in polyurethanes (PUs) through in-situ self-crosslinking still requires improvement and heavily relies on petroleum-derived feedstocks in certain approaches.

Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles.

Rho GTPases play a key role in the spatio-temporal coordination of cytoskeletal dynamics during cell migration. Here, we directly investigate crosstalk between the major Rho GTPases Rho, Rac and Cdc42 by combining rapid activity perturbation with activity measurements in mammalian cells. These studies reveal that Rac stimulates Rho activity.

ATG12-ATG5-TECPR1: an alternative E3-like complex utilized during the cellular response to lysosomal membrane damage.

ATG16L1 is an essential component of the Atg8-family protein conjugation machinery, providing membrane targeting for the ATG12-ATG5 conjugate. Recently, we identified an alternative E3-like complex that functions independently of ATG16L1. This complex utilizes the autophagosome-lysosome tethering factor TECPR1 for membrane targeting.

Inducin Triggers LC3-Lipidation and ESCRT-Mediated Lysosomal Membrane Repair.

Lipidation of the LC3 protein has frequently been employed as a marker of autophagy. However, LC3-lipidation is also triggered by stimuli not related to canonical autophagy. Therefore, characterization of the driving parameters for LC3 lipidation is crucial to understanding the biological roles of LC3.

An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes.

Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms to maintain lysosomal integrity. Small membrane lesions are detected and repaired by the endosomal sorting complex required for transport (ESCRT) machinery while more extensively damaged lysosomes are cleared by a galectin-dependent selective macroautophagic pathway (lysophagy).

Eating while intoxicated: characterizing the molecular mechanism behind toxin MakA-regulated autophagy.

Extracellular pathogens utilize secreted virulence factors to regulate host cell function. Recently we characterized the molecular mechanism behind host macroautophagy/autophagy regulation by the toxin MakA. Cholesterol binding at the plasma membrane induces MakA endocytosis and pH-dependent pore assembly.

V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy.

Pore-forming toxins (PFTs) are important virulence factors produced by many pathogenic bacteria. Here, we show that the Vibrio cholerae toxin MakA is a novel cholesterol-binding PFT that induces non-canonical autophagy in a pH-dependent manner. MakA specifically binds to cholesterol on the membrane at pH < 7.

Bio-Based, Recyclable and Self-Healing Polyurethane Composites with High Energy Dissipation and Shape Memory.

Rubber composites make an important contribution to eliminating vibration and noise owing to their unique viscoelasticity. However, it is important to find alternative bio-based products with high damping properties owing to the shortage of petrochemical resources and poor performance. The ability to self-heal is an additional characteristic that is highly desirable because it can further increase the service life and safety of such products.

Nonenzymatic Browning of Amorphous Maltose/Whey Protein Isolates Matrix: Effects of Water Sorption and Molecular Mobility.

Nonenzymatic browning (NEB) reactions often affect the nutritional quality and safety properties of amorphous food solids. Developing a proper approach to control the NEB reaction has been of particular interest in the food industry. An NEB reaction in an amorphous maltose/Whey protein isolates (WPI) matrix containing L-lysine and D-xylose as reactants were studied at ambient temperatures ≤ 0.

Ultrafast and selective labeling of endogenous proteins using affinity-based benzotriazole chemistry.

Chemical modification of proteins is enormously useful for characterizing protein function in complex biological systems and for drug development. Selective labeling of native or endogenous proteins is challenging owing to the existence of distinct functional groups in proteins and in living systems. Chemistry for rapid and selective labeling of proteins remains in high demand.

Bio-Based Polyurethane and Its Composites towards High Damping Properties.

The operation of mechanical equipment inevitably generates vibrations and noise, which are harmful to not only the human body but also to the equipment in use. Damping materials, which can convert mechanical energy into thermal energy, possess excellent damping properties in the glass transition region and can alleviate the problems caused by vibration and noise. However, these materials mainly rely on petroleum-based resources, and their glass transition temperatures () are lower than room temperature.

Physicochemical properties and Strength analysis of vitreous encapsulated solids for the safe delivery of β-Carotene.

β-Carotene (β-Car) is insoluble compounds in water and liable to degradation, which has health benefits for human beings. Although layer-by-layer (LBL) emulsions provide a better protection for β-Car towards environmental stresses, the handling and transportation of LBL emulsions still faces restrictions. In this paper, therefore, the LBL emulsions including β-Car were carefully prepared and encapsulated to obtain vitreous encapsulated solids (VES) using trehalose and maltodextrins (MD) as wall materials.

Synthesis of 20-Membered Macrocyclic Pseudo-Natural Products Yields Inducers of LC3 Lipidation.

Design and synthesis of pseudo-natural products (PNPs) through recombination of natural product (NP) fragments in unprecedented arrangements enables the discovery of novel biologically relevant chemical matter. With a view to wider coverage of NP-inspired chemical and biological space, we describe the combination of this principle with macrocycle formation. PNP-macrocycles were synthesized efficiently in a stereoselective one-pot procedure including the 1,3-dipolar cycloadditions of different dipolarophiles with dimeric cinchona alkaloid-derived azomethine ylides formed in situ.

Monitoring the Response of Multiple Signal Network Components to Acute Chemo-Optogenetic Perturbations in Living Cells.

Cells process information via signal networks that typically involve multiple components which are interconnected by feedback loops. The combination of acute optogenetic perturbations and microscopy-based fluorescent response readouts enables the direct investigation of causal links in such networks. However, due to overlaps in spectra of photosensitive and fluorescent proteins, current approaches that combine these methods are limited.

Biobased and Recyclable Polyurethane for Room-Temperature Damping and Three-Dimensional Printing.

Petroleum-based polymer materials heavily rely on nonrenewable petrochemical resources, and damping materials are an important category of them. As far as green chemistry, recycling, and damping materials are concerned, there is an urgent need for renewable and recyclable biobased materials with high damping performance. Thus, this study designs and synthesizes a series of polylactic acid-based thermoplastic polyurethanes (PLA-based TPUs) composed of modified polylactic acid polyols, 4,4'-diphenylmethane diisocyanate, and 1,4-butanediol.

Imaging of Spatial Cycling of Rab GTPase in the Cell.

Rab GTPases (>60 members in human) function as master regulators of intracellular membrane trafficking. To fulfill their functions, Rab proteins need to localize on specific membranes in cells. It remains elusive how the distinct spatial distribution of Rab GTPases in the cell is regulated.

Color-based clustering algorithm as a novel image analytical method for characterizing maltose crystallinity in amorphous food models.

Maltose crystallization affects the processibility and stability of sugar-rich foods. This study introduced a color-based clustering algorithm (CCA) to analyze crystallinity from the images of amorphous maltose/protein models. The XRD and DSC were also implemented in maltose crystallization characterization and validated the CCA analysis.

Spatiotemporal Imaging of Small GTPase Activity Using Conformational Sensors for GTPase Activity (COSGA).

Small GTPases cycle between active GTP bound and inactive GDP bound forms in live cells. They act as molecular switches and regulate diverse cellular processes at different times and locations in the cell. Spatiotemporal visualization of their activity provides important insights into dynamics of cellular signaling.

Thermal proteome profiling identifies the membrane-bound purinergic receptor P2X4 as a target of the autophagy inhibitor indophagolin.

Signaling pathways are frequently activated through signal-receiving membrane proteins, and the discovery of small molecules targeting these receptors may yield insights into their biology. However, due to their intrinsic properties, membrane protein targets often cannot be identified by means of established approaches, in particular affinity-based proteomics, calling for the exploration of new methods. Here, we report the identification of indophagolin as representative member of an indoline-based class of autophagy inhibitors through a target-agnostic phenotypic assay.