Biomimetic Design of Artificial Hybrid Nanocells for Boosted Vascular Regeneration in Ischemic Tissues.

Restoration of sufficient blood supply for the treatment of ischemia remains a significant scientific and clinical challenge. Here, a cell-like nanoparticle delivery technology is introduced that is capable of recapitulating multiple cell functions for the spatiotemporal triggering of vascular regeneration. Specifically, a copper-containing protein is successfully prepared using a recombinant protein scaffold based on a de novo design strategy, which facilitates the timely release of nitric oxide and improved accumulation of particles within ischemic tissues.

Experimental mapping of short-wavelength phonons in proteins.

Phonons are quasi-particles, observed as lattice vibrations in periodic materials, that often dampen in the presence of structural perturbations. Nevertheless, phonon-like collective excitations exist in highly complex systems, such as proteins, although the origin of such collective motions has remained elusive. Here we present a picture of temperature and hydration dependence of collective excitations in green fluorescent protein (GFP) obtained by inelastic neutron scattering.

In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins.

Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (Na) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions.

Methanol carbonylation to acetaldehyde on Au particles supported by single-layer MoSgrown on silica.

Homogenous single-layer MoSfilms coated with sub-single layer amounts of gold are found to isolate the reaction of methanol with carbon monoxide, the fundamental step toward higher alcohols, from an array of possible surface reactions. Active surfaces were prepared from homogenous single-layer MoSfilms coated with sub-single layer amounts of gold. These gold atoms formed clusters on the MoSsurface.

Immunology and Immunotherapy of Endometriosis.

Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future.

Photothermal Conjugated Polymer Nanoparticles for Suppressing Breast Tumor Growth by Regulating TRPA1 Ion Channels.

Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS-sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca which upregulates the anti-apoptotic pathway to lead breast cancer cells to produce oxidative stress defense and enhance the resistance to ROS related chemotherapy. Targeting and inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcoming cellular resistance.

A Model for the Signal Initiation Complex Between Arrestin-3 and the Src Family Kinase Fgr.

Arrestins regulate a wide range of signaling events, most notably when bound to active G protein-coupled receptors (GPCRs). Among the known effectors recruited by GPCR-bound arrestins are Src family kinases, which regulate cellular growth and proliferation. Here, we focus on arrestin-3 interactions with Fgr kinase, a member of the Src family.

Stable Aqueous Colloidal Solutions of Nd: LaF Nanoparticles, Promising for Luminescent Bioimaging in the Near-Infrared Spectral Range.

Two series of stable aqueous colloidal solutions of Nd: LaF single-phase well-crystallized nanoparticles (NPs), possessing a fluorcerite structure with different activator concentrations in each series, were synthesized. A hydrothermal method involving microwave-assisted heating (HTMW) in two Berghof speedwave devices equipped with one magnetron (type I) or two magnetrons (type II) was used. The average sizes of NPs are 15.

Attractive internuclear force drives the collective behavior of nuclear arrays in Drosophila embryos.

The collective behavior of the nuclear array in Drosophila embryos during nuclear cycle (NC) 11 to NC14 is crucial in controlling cell size, establishing developmental patterns, and coordinating morphogenesis. After live imaging on Drosophila embryos with light sheet microscopy, we extract the nuclear trajectory, speed, and internuclear distance with an automatic nuclear tracing method. We find that the nuclear speed shows a period of standing waves along the anterior-posterior (AP) axis after each metaphase as the nuclei collectively migrate towards the embryo poles and partially move back.

Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate.

Pulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO) in PH are lacking.

Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer.

Tumor microenvironments shape aggressiveness and are largely maintained by the conditions of angiogenesis formation. Thus, endothelial cells' (ECs) biological reactions are crucial to understand and control the design of efficient therapies. In this work, we used models of ECs to represent a breast cancer tumor site as well as the same, healthy tissue.

Correlated Response of Protein Side-Chain Fluctuations and Conformational Entropy to Ligand Binding.

The heterogeneous fast side-chain dynamics of proteins plays crucial roles in molecular recognition and binding. Site-specific NMR experiments quantify these motions by measuring the model-free order parameter () on a scale of 0 (most flexible) to 1 (least flexible) for each methyl-containing residue of proteins. Here, we have examined ligand-induced variations in the fast side-chain dynamics and conformational entropy of calmodulin (CaM) using five different CaM-peptide complexes.

Lpp positions peptidoglycan at the AcrA-TolC interface in the AcrAB-TolC multidrug efflux pump.

The multidrug efflux pumps of Gram-negative bacteria are a class of complexes that span the periplasm, coupling both the inner and outer membranes to expel toxic molecules. The best-characterized example of these tripartite pumps is the AcrAB-TolC complex of Escherichia coli. However, how the complex interacts with the peptidoglycan (PG) cell wall, which is anchored to the outer membrane (OM) by Braun's lipoprotein (Lpp), is still largely unknown.

Design of Broadly Cross-Reactive M Protein-Based Group A Streptococcal Vaccines.

Group A streptococcal infections are a significant cause of global morbidity and mortality. A leading vaccine candidate is the surface M protein, a major virulence determinant and protective Ag. One obstacle to the development of M protein-based vaccines is the >200 different M types defined by the N-terminal sequences that contain protective epitopes.

Monitoring Human Neutrophil Activation by a Proteinase 3 Near-Infrared Fluorescence Substrate-Based Probe.

A near-infrared fluorescent (NIRF) substrate-based probe (SBP) was conceived to monitor secreted human proteinase 3 (hPR3) activity. This probe, called pro3-SBP, is shaped by a fused peptide hairpin loop structure, which associates a hPR3 recognition domain (Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln, where Nva is norvaline) and an electrostatic zipper (consisting of complementary polyanionic (d-Glu) and polycationic (d-Arg) sequences) in close vicinity of the N- and C-terminal FRET couple (fluorescent donor, sulfoCy5.5; dark quencher, QSY21).

Protein conformational switch discerned via network centrality properties.

Network analysis has emerged as a powerful tool for examining structural biology systems. The spatial organization of the components of a biomolecular structure has been rendered as a graph representation and analyses have been performed to deduce the biophysical and mechanistic properties of these components. For proteins, the analysis of protein structure networks (PSNs), especially via network centrality measurements and cluster coefficients, has led to identifying amino acid residues that play key functional roles and classifying amino acid residues in general.

Research progress of STC2 in breast cancer.

Breast cancer ranks second in the list of most common cancers among women and brings the double burden of economy and health to women. Therefore, it is an urgent and necessary task to study the pathogenic mechanism and the treatment of breast cancer. Glycoprotein hormone is a kind of hormones to promote the growth and the development of cell and stanniocalcin 2 (STC2) is one of them.

Mechanistic Investigation of Dimethylmercury Formation Mediated by a Sulfide Mineral Surface.

Mercury (Hg) pollution is a global environmental problem. The abiotic formation of dimethylmercury (DMeHg) from monomethylmercury (MMeHg) may account for a large portion of DMeHg in oceans. Previous experimental work has shown that abiotic formation of DMeHg from MMeHg can be facilitated by reduced sulfur groups on sulfide mineral surfaces.

Machine Learning Reveals the Critical Interactions for SARS-CoV-2 Spike Protein Binding to ACE2.

SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Herein, we have used molecular dynamics (MD) simulations, machine learning (ML), and free-energy perturbation (FEP) calculations to elucidate the differences in binding by the two viruses. Although only subtle differences were observed from the initial MD simulations of the two RBD-ACE2 complexes, ML identified the individual residues with the most distinctive ACE2 interactions, many of which have been highlighted in previous experimental studies.

Tuning Proton Transfer Thermodynamics in SARS-CoV-2 Main Protease: Implications for Catalysis and Inhibitor Design.

The catalytic reaction in SARS-CoV-2 main protease is activated by a proton transfer (PT) from Cys145 to His41. The same PT is likely also required for the covalent binding of some inhibitors. Here we use a multiscale computational approach to investigate the PT thermodynamics in the apo enzyme and in complex with two potent inhibitors, N3 and the α-ketoamide .

In Vivo bone tissue induction by freeze-dried collagen-nanohydroxyapatite matrix loaded with BMP2/NS1 mRNAs lipopolyplexes.

Messenger RNA (mRNA) activated matrices (RAMs) are interesting to orchestrate tissue and organ regeneration due to the in-situ and sustained production of functional proteins. However, the immunogenicity of in vitro transcribed mRNA and the paucity of proper in vivo mRNA delivery vector need to be overcome to exert the therapeutic potential of RAM. We developed a dual mRNAs system for in vitro osteogenesis by co-delivering NS1 mRNA with BMP2 mRNA to inhibit RNA sensors and enhance BMP-2 expression.

Reproducibility and accuracy of microscale thermophoresis in the NanoTemper Monolith: a multi laboratory benchmark study.

Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.

Cross-reactive immunogenicity of group A streptococcal vaccines designed using a recurrent neural network to identify conserved M protein linear epitopes.

The M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal sequence of the protein defines the more than 200 M types of Strep A and also contains epitopes that elicit opsonic antibodies, some of which cross-react with heterologous M types. Current efforts to develop broadly protective M protein-based vaccines are directed at identifying potential cross-protective epitopes located in the N-terminal regions of cluster-related M proteins for use as vaccine antigens.