Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.

Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).

Blobby is a synaptic active zone assembly protein required for memory in Drosophila.

At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, "Blobby", essential for proper AZ nano-organization.

Antigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange.

Major histocompatibility complex class II (MHC-II) presents antigens to T helper cells. The spectrum of presented peptides is regulated by the exchange catalyst human leukocyte antigen DM (HLA-DM), which dissociates peptide-MHC-II complexes in the endosome. How susceptible a peptide is to HLA-DM is mechanistically not understood.

Design of facilitated dissociation enables control over cytokine signaling duration.

Protein design has focused primarily on the design of ground states, ensuring they are sufficiently low energy to be highly populated. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that are traversed in transitions from one low-lying state to another. This is a challenging task as such states must be sufficiently strained to be poorly populated, but not so strained that they are not populated at all, and because protein design methods have generally focused on creating near-ideal structures.

Prognostic implications of a CD8 T to CD4T imbalance in mandibular fracture healing: a prospective analysis of immune profiles.

Introduction: Open reduction and fixation are the standard of care for treating mandibular fractures and usually lead to successful healing. However, complications such as delayed healing, non-union, and infection can compromise patient outcomes and increase healthcare costs. The initial inflammatory response, particularly the response involving specific CD8 T cell subpopulations, is thought to play a critical role in healing long bone fractures.

Asparagusic Golgi Trackers.

Thiol-mediated uptake (TMU) is thought to occur through dynamic covalent cascade exchange networks. Here we show that the cascade accounting for TMU of asparagusic acid derivatives (AspA) ends in the Golgi apparatus (G) and shifts from disulfide to thioester exchange with palmitoyl transferases as the final exchange partner. As a result, AspA combined with pH-sensitive fluoresceins, red-shifted silicon-rhodamines, or mechanosensitive flipper probes selectively labels the Golgi apparatus in fluorescence microscopy images in living and fixed cells.

Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation.

The lymphatic system is formed during embryonic development by the commitment of specialized lymphatic endothelial cells (LECs) and their subsequent assembly in primary lymphatic vessels. Although lymphatic cells are in continuous contact with mesenchymal cells during development and in adult tissues, the role of mesenchymal cells in lymphatic vasculature development remains poorly characterized. Here, we show that a subpopulation of mesenchymal cells expressing the transcription factor Osr1 are in close association with migrating LECs and established lymphatic vessels in mice.

Temporal regulation of BMP2 growth factor signaling in response to mechanical loading is linked to cytoskeletal and focal adhesion remodeling.

Biophysical cues have the ability to enhance cellular signaling response to Bone Morphogenetic Proteins, an essential growth factor during bone development and regeneration. Yet, therapeutic application of Bone Morphogenetic Protein 2 (BMP2) is restricted due to uncontrolled side effects. An understanding of the temporal characteristics of mechanically regulated signaling events and underlying mechanism is lacking.

When less is more - a fast TurboID knock-in approach for high-sensitivity endogenous interactome mapping.

In recent years, proximity labeling has established itself as an unbiased and powerful approach to map the interactome of specific proteins. Although physiological expression of labeling enzymes is beneficial for the mapping of interactors, generation of the desired cell lines remains time-consuming and challenging. Using our established pipeline for rapid generation of C- and N-terminal CRISPR-Cas9 knock-ins (KIs) based on antibiotic selection, we were able to compare the performance of commonly used labeling enzymes when endogenously expressed.

Bacterial epigenetics and its implication for agriculture, probiotics development, and biotechnology design.

In their natural habitats, organisms encounter numerous external stimuli and must be able to sense and adapt to those stimuli to survive. Unlike mutations, epigenetic changes do not alter the underlying DNA sequence. Instead, they create modifications that promote or silence gene expression.

Fraternal twins at work: Structures of PLD3/4 reveal mechanism for lysosomal nucleic acid breakdown.

Phospholipase D (PLD) family proteins degrade phospholipids and nucleic acids. In the current issue of Structure, Yuan et al. report crystal structures of lysosomal PLD3 and PLD4 with and without a single-stranded DNA substrate.

Automated Analysis of Neuronal Morphology in 2D Fluorescence Micrographs through an Unsupervised Semantic Segmentation of Neurons.

Brain function emerges from a highly complex network of specialized cells that are interlinked by billions of synapses. The synaptic connectivity between neurons is established between the elongated processes of their axons and dendrites or, together, neurites. To establish these connections, cellular neurites have to grow in highly specialized, cell-type dependent patterns covering extensive distances and connecting with thousands of other neurons.

Correlating semiconductor nanoparticle architecture and applicability for the controlled encoding of luminescent polymer microparticles.

Luminophore stained micro- and nanobeads made from organic polymers like polystyrene (PS) are broadly used in the life and material sciences as luminescent reporters, for bead-based assays, sensor arrays, printable barcodes, security inks, and the calibration of fluorescence microscopes and flow cytometers. Initially mostly prepared with organic dyes, meanwhile luminescent core/shell nanoparticles (NPs) like spherical semiconductor quantum dots (QDs) are increasingly employed for bead encoding. This is related to their narrower emission spectra, tuneability of emission color, broad wavelength excitability, and better photostability.

Mechanical heterogeneity in a soft biomaterial niche controls BMP2 signaling.

The extracellular matrix is known to impact cell function during regeneration by modulating growth factor signaling. However, how the mechanical properties and structure of biomaterials can be used to optimize the cellular response to growth factors is widely neglected. Here, we engineered a macroporous biomaterial to study cellular signaling in environments that mimic the mechanical stiffness but also the mechanical heterogeneity of native extracellular matrix.

First-Principles Study of Adsorption of CH on a Fluorinated Model NiF Surface.

Electrochemical fluorination on nickel anodes, also known as the Simons' process, is an important fluorination method used on an industrial scale. Despite its success, the mechanism is still under debate. One of the proposed mechanisms involves higher valent nickel species formed on an anode acting as effective fluorinating agents.

Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α.

Chinese hamster ovary (CHO) cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational modifications. However, toxic proteins and membrane proteins are often difficult-to-express in living cells. Alternatively, cell-free protein synthesis can be employed.

Photoswitchable Endocytosis of Biomolecular Condensates in Giant Vesicles.

Interactions between membranes and biomolecular condensates can give rise to complex phenomena such as wetting transitions, mutual remodeling, and endocytosis. In this study, light-triggered manipulation of condensate engulfment is demonstrated using giant vesicles containing photoswitchable lipids. UV irradiation increases the membrane area, which can be stored in nanotubes.

Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination.

In neurons, the microtubule (MT) cytoskeleton forms the basis for long-distance protein transport from the cell body into and out of dendrites and axons. To maintain neuronal polarity, the axon initial segment (AIS) serves as a physical barrier, separating the axon from the somatodendritic compartment and acting as a filter for axonal cargo. Selective trafficking is further instructed by axonal enrichment of MT post-translational modifications, which affect MT dynamics and the activity of motor proteins.

Easy Synthetic Access to High-Melting Sulfurated Copolymers and their Self-Assembling Diblock Copolymers from Phenylisothiocyanate and Oxetane.

Although sulfurated polymers promise unique properties, their controlled synthesis, particularly when it comes to complex and functional architectures, remains challenging. Here, we show that the copolymerization of oxetane and phenyl isothiocyanate selectively yields polythioimidocarbonates as a new class of sulfur containing polymers, with narrow molecular weight distributions (M=5-80 kg/mol with Đ≤1.2; M=124 kg/mol) and high melting points of up to 181 °C.

Reduced Protein Stability of 11 Pathogenic Missense STXBP1/MUNC18-1 Variants and Improved Disease Prediction.

Background: Pathogenic variants in STXBP1/MUNC18-1 cause severe encephalopathies that are among the most common in genetic neurodevelopmental disorders. Different molecular disease mechanisms have been proposed, and pathogenicity prediction is limited. In this study, we aimed to define a generalized disease concept for STXBP1-related disorders and improve prediction.

Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.

Recurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation.