Electrosynthesis of Mussel-inspired Adhesive Polymers as a Novel Class of Transient Enzyme Stabilizers.

Multifunctional ortho-quinones are required for the formation of thiol-catechol-connectivities (TCC) but can be delicate to handle. We present the electrochemical oxidation of the dipeptide DiDOPA, achieving up to 92 % conversion efficiency of the catechols to ortho-quinones. Graphite and stainless steel could be employed as cost-efficient electrodes.

Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation.

The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function.

Spns1 is an iron transporter essential for megalin-dependent endocytosis.

Proximal tubule endocytosis is essential to produce protein-free urine as well as to regulate system-wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules.

Polarity transitions of narrow bipolar events in thundercloud tops reaching the lower stratosphere.

Blue corona discharges are often generated in thunderclouds penetrating into the stratosphere and are the optical manifestation of narrow bipolar events (NBEs) observed in radio signals. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we show the observations by a lightning detection array of unusual amounts of 982 NBEs during a tropical storm on the coastline of China.

No signs of microbial-influenced corrosion of cast iron and copper in bentonite microcosms after 400 days.

High-level radioactive waste needs to be safely stored for a long time in a deep geological repository by using a multi-barrier system. In this system, suitable barrier materials are selected that ideally show long-term stability to prevent early radionuclide release into the biosphere. In this study, different container matals (copper and cast iron) and pore water compositions (Opalinus Clay pore water and saline cap rock solution) were combined with Bavarian bentonite in static batch experiments to investigate microbial-influenced corrosion.

Redox-Triggered Debonding of Mussel-Inspired Pressure Sensitive Adhesives: Improving Efficiency Through Functional Design.

Debondable pressure-sensitive adhesives (PSAs) promise access to recyclability in microelectronics in the transition toward a circular economy. Two PSAs were synthesized from a tetravalent thiol star-polyester forming thiol-catechol-connectivities (TCC) with either the biorelated DiDopa-bisquinone (BY*Q) or the fossil-based bisquinone A (BQA). The PSAs enable debonding by oxidation of TCC-catechols to quinones.

Functionally distinct pericyte subsets differently regulate amyloid-β deposition in patients with Alzheimer's disease.

Although the concept that the blood-brain barrier (BBB) plays an important role in the etiology and pathogenesis of Alzheimer's disease (AD) has become increasingly accepted, little is known yet about how it actually contributes. We and others have recently identified a novel functionally distinct subset of BBB pericytes (PCs). In the present study, we sought to determine whether these PC subsets differentially contribute to AD-associated pathologies by immunohistochemistry and amyloid beta (Aβ) peptidomics.

Modulation of GPR133 (ADGRD1) signaling by its intracellular interaction partner extended synaptotagmin 1.

GPR133 (ADGRD1) is an adhesion G-protein-coupled receptor that signals through Gαs/cyclic AMP (cAMP) and is required for the growth of glioblastoma (GBM), an aggressive brain malignancy. The regulation of GPR133 signaling is incompletely understood. Here, we use proximity biotinylation proteomics to identify ESYT1, a Ca-dependent mediator of endoplasmic reticulum-plasma membrane bridge formation, as an intracellular interactor of GPR133.

Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function.

Optically induced charge-transfer in donor-acceptor-substituted p- and m- CBH carboranes.

Icosahedral carboranes, CBH, have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster.

Employing optical lightning data to identify lightning flashes associated to terrestrial gamma-ray flashes.

Terrestrial gamma-ray flashes (TGFs) are bursts of energetic X- and gamma-rays emitted from thunderstorms. The Atmosphere-Space Interactions Monitor (ASIM) mounted onto the International Space Station (ISS) is dedicated to measure TGFs and optical signatures of lightning; ISS LIS (Lightning Imaging Sensor) detects lightning flashes allowing for simultaneous measurements with ASIM. Whilst ASIM measures 300-400 TGFs per year, ISS LIS detects annual lightning flashes giving a disproportion of four orders of magnitude.

VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain.

Phosphorylation of hundreds of protein extracellular domains is mediated by two kinase families, yet the significance of these kinases is underexplored. Here, we find that the presynaptic release of the tyrosine directed-ectokinase, Vertebrate Lonesome Kinase (VLK/Pkdcc), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses, for phosphorylation of the ectodomain of EphB2, and for injury-induced pain. is an essential gene in the nervous system, and VLK is found in synaptic vesicles, and is released from neurons in a SNARE-dependent fashion.

Imaging of 3 bright terrestrial gamma-ray flashes by the atmosphere-space interactions monitor and their parent thunderstorms.

The Atmosphere-Space Interactions Monitor (ASIM) on the International Space Station (ISS) includes an instrument designed to geolocate Terrestrial Gamma-ray Flashes (TGF) produced by thunderstorms. It does so with a coded aperture system shadowing the pixelated Low Energy Detector of the Modular X- and Gamma-ray Sensor (MXGS). Additionally, it locates associated lightning flashes with the Modular Multispectral Imaging Array (MMIA).

Real-Time Monitoring of Cell Adhesion onto a Soft Substrate by a Graphene Impedance Biosensor.

Soft substrates are interesting for many applications, ranging from mimicking the cellular microenvironment to implants. Conductive electrodes on such substrates allow the realization of flexible, elastic, and transparent sensors. Single-layer graphene as a candidate for such electrodes brings the advantage that the active area of the sensor is transparent and conformal to the underlying substrate.

Electrochemistry at the Edge of a van der Waals Heterostructure.

Artificial van der Waals heterostructures, obtained by stacking two-dimensional (2D) materials, represent a novel platform for investigating physicochemical phenomena and applications. Here, the electrochemistry at the one-dimensional (1D) edge of a graphene sheet, sandwiched between two hexagonal boron nitride (hBN) flakes, is reported. When such an hBN/graphene/hBN heterostructure is immersed in a solution, the basal plane of graphene is encapsulated by hBN, and the graphene edge is exclusively available in the solution.

Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human.

Astrocytes are a heterogeneous population of central nervous system glial cells that respond to pathological insults and injury by undergoing a transformation called "reactivity." Reactive astrocytes exhibit distinct and context-dependent cellular, molecular, and functional state changes that can either support or disturb tissue homeostasis. We recently identified a reactive astrocyte sub-state defined by interferon-responsive genes like Igtp, Ifit3, Mx1, and others, called interferon-responsive reactive astrocytes (IRRAs).

The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model.

Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model.

Cardiolipin prolongs the lifetimes of respiratory proteins in Drosophila flight muscle.

Respiratory complexes and cardiolipins have exceptionally long lifetimes. The fact that they co-localize in mitochondrial cristae raises the question of whether their longevities have a common cause and whether the longevity of OXPHOS proteins is dependent on cardiolipin. To address these questions, we developed a method to measure side-by-side the half-lives of proteins and lipids in wild-type Drosophila and cardiolipin-deficient mutants.

Statistical Copolymers that Mimic Aspects of Mussel Adhesive Proteins: Access to Robust Adhesive-Domains for Non-Covalent Surface PEGylation.

Reconstructing functional sequence motifs of proteins, using statistical copolymers greatly reduces the information content, but simplifies synthesis significantly. Key amino acid residues involved in the adhesion of mussel foot proteins are identified. The side-chain functionalities of Dopa, lysine, and arginine are abstracted and incorporated into acrylate monomers to allow controlled radical polymerization.

Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by Tyr-phosphorylated APP βCTF.

Lysosome dysfunction arises early and propels Alzheimer's disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome (DS), acts directly via its β-C-terminal fragment (βCTF) to disrupt lysosomal vacuolar (H)-adenosine triphosphatase (v-ATPase) and acidification. In human DS fibroblasts, the phosphorylated YENPTY internalization motif of APP-βCTF binds selectively within a pocket of the v-ATPase V0a1 subunit cytoplasmic domain and competitively inhibits association of the V1 subcomplex of v-ATPase, thereby reducing its activity.

PTK7 is a positive allosteric modulator of GPR133 signaling in glioblastoma.

The adhesion G-protein-coupled receptor GPR133 (ADGRD1) supports growth of the brain malignancy glioblastoma. How the extracellular interactome of GPR133 in glioblastoma modulates signaling remains unknown. Here, we use affinity proteomics to identify the transmembrane protein PTK7 as an extracellular binding partner of GPR133 in glioblastoma.

Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.

Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights.

Comparing synaptic proteomes across five mouse models for autism reveals converging molecular similarities including deficits in oxidative phosphorylation and Rho GTPase signaling.

Specific and effective treatments for autism spectrum disorder (ASD) are lacking due to a poor understanding of disease mechanisms. Here we test the idea that similarities between diverse ASD mouse models are caused by deficits in common molecular pathways at neuronal synapses. To do this, we leverage the availability of multiple genetic models of ASD that exhibit shared synaptic and behavioral deficits and use quantitative mass spectrometry with isobaric tandem mass tagging (TMT) to compare their hippocampal synaptic proteomes.

Global Distribution of Key Features of Streamer Corona Discharges in Thunderclouds.

We present nighttime worldwide distributions of key features of Blue LUminous Events (BLUEs) detected by the Modular Multispectral Imaging Array of the Atmosphere-Space Interaction Monitor. Around 10% of all detected BLUEs exhibit an impulsive single pulse shape. The rest of BLUEs are unclear (impulsive or not) single, multiple or with ambiguous pulse shapes.