Short-Term Effect of SARS-CoV-2 Spike Protein Receptor-Binding Domain-Specific Antibody Induction on Neutrophil-Mediated Immune Response in Mice

Vaccination protects against COVID-19 via the spike protein receptor-binding domain (RBD)-specific antibody formation, but it also affects the innate immunity. The effects of specific antibody induction on neutrophils that can cause severe respiratory inflammation are important, though not completely investigated. In the present study, using a mouse model mimicking SARS-CoV-2 virus particle inhalation, we investigated neutrophil phenotype and activity alterations in the presence of RBD-specific antibodies. Mice were immunized with RBD and a week after a strong antibody response establishment received 100 nm particles in the RBD solution. Control mice received injections of a phosphate buffer instead of RBD. We show that the application of 100 nm particles in the RBD solution elevates neutrophil recruitment to the blood and the airways of RBD-immunized mice rather than in control mice. Analysis of bone marrow cells of mice with induced RBD-specific antibodies revealed the increased population of CXCR2+CD101+ neutrophils. These neutrophils did not demonstrate an enhanced ability of neutrophil extracellular traps (NETs) formation compared to the neutrophils from control mice. Thus, the induction of RBD-specific antibodies stimulates the activation of mature neutrophils that react to RBD-coated particles without triggering excessive inflammation

Murine Intraepithelial Dendritic Cells Interact With Phagocytic Cells During Aspergillus fumigatus-Induced Inflammation

People are constantly exposed to airborne fungal spores, including Aspergillus fumigatus conidia that can cause life-threatening conditions in immunocompromised patients or acute exacerbations in allergics. However, immunocompetent hosts do not exhibit mycoses or systemic inflammation, due to the sufficient but not excessive antifungal immune response that prevent fungal invasion. Intraepithelial dendritic cells (IE-DCs) of the conducting airway mucosa are located in the primary site of the inhalant pathogen entry; these cells can sense A. fumigatus conidia and maintain homeostasis. The mechanisms by which IE-DCs contribute to regulating the antifungal immune response and controlling conidia dissemination are not understood. To clarify the role of IE-DCs in the balance between pathogen sensing and immune tolerance we investigated the A. fumigatus conidia distribution in optically cleared mouse lungs and estimated the kinetics of the local phagocytic response during the course of inflammation. MHCII+ antigen-presenting cells, including IE-DCs, and CD11b+ phagocytes were identified by immunohistochemistry and three-dimensional fluorescence confocal laser-scanning microscopy of conducting airway whole-mounts. Application of A. fumigatus conidia increased the number of CD11b+ phagocytes in the conducting airway mucosa and induced the trafficking of these cells through the conducting airway wall to the luminal side of the epithelium. Some CD11b+ phagocytes internalized conidia in the conducting airway lumen. During the migration through the airway wall, CD11b+ phagocytes formed clusters. Permanently located in the airway wall IE-DCs contacted both single CD11b+ phagocytes and clusters. Based on the spatiotemporal characteristics of the interactions between IE-DCs and CD11b+ phagocytes, we provide a novel anatomical rationale for the contribution of IE-DCs to controlling the excessive phagocyte-mediated immune response rather than participating in pathogen uptake

All - d - Enantiomeric Peptide D3 Designed for Alzheimer’s Disease Treatment Dynamically Interacts with Membrane-Bound Amyloid-β Precursors

Alzheimer’s disease (AD) is a severe neurodegenerative pathology with no effective treatment known. Toxic amyloid-β peptide (Aβ) oligomers play a crucial role in AD pathogenesis. All-d-Enantiomeric peptide D3 and its derivatives were developed to disassemble and destroy cytotoxic Aβ aggregates. One of the D3-like compounds is approaching phase II clinical trials; however, high-resolution details of its disease-preventing or pharmacological actions are not completely clear. We demonstrate that peptide D3 stabilizing Aβ monomer dynamically interacts with the extracellular juxtamembrane region of a membrane-bound fragment of an amyloid precursor protein containing the Aβ sequence. MD simulations based on NMR measurement results suggest that D3 targets the amyloidogenic region, not compromising its α-helicity and preventing intermolecular hydrogen bonding, thus creating prerequisites for inhibition of early steps of Aβ conversion into β-conformation and its toxic oligomerization. An enhanced understanding of the D3 action molecular mechanism facilitates development of effective AD treatment and prevention strategies

Mirror proteorhodopsins

Abstract Proteorhodopsins (PRs), bacterial light-driven outward proton pumps comprise the first discovered and largest family of rhodopsins, they play a significant role in life on the Earth. A big remaining mystery was that up-to-date there was no described bacterial rhodopsins pumping protons at acidic pH despite the fact that bacteria live in different pH environment. Here we describe conceptually new bacterial rhodopsins which are operating as outward proton pumps at acidic pH. A comprehensive function-structure study of a representative of a new clade of proton pumping rhodopsins which we name “mirror proteorhodopsins”, from Sphingomonas paucimobilis (SpaR) shows cavity/gate architecture of the proton translocation pathway rather resembling channelrhodopsins than the known rhodopsin proton pumps. Another unique property of mirror proteorhodopsins is that proton pumping is inhibited by a millimolar concentration of zinc. We also show that mirror proteorhodopsins are extensively represented in opportunistic multidrug resistant human pathogens, plant growth-promoting and zinc solubilizing bacteria. They may be of optogenetic interest

Study of strange matter production in the heavy ion collisions at NUCLOTRON

It is proposed to install an experimental setup in the fixed-target hall of the Nuclotron with the final goal to perform a research program focused on the production of strange matter in heavyion collisions at beam energies between 2 and 6 A GeV. The basic setup will comprise a large acceptance dipole magnet with inner tracking detector modules based on double-sided Silicon micro-strip sensors and GEMs. The outer tracking will be based on the drift chambers and straw tube detector. Particle identification will be based on the time-of-flight measurements. This setup will be sufficient perform a comprehensive study of strangeness production in heavy-ion collisions, including multi-strange hyperons, multi-strange hypernuclei, and exotic multi-strange heavy objects. These pioneering measurements would provide the first data on the production of these particles in heavy-ion collisions at Nuclotron beam energies, and would open an avenue to explore the third (strangeness) axis of the nuclear chart. The extension of the experimental program is related with the study of in-medium effects for vector mesons decaying in hadronic modes. The studies of the NN and NA reactions for the reference is assumed

Transverse polarisation measurement of Λ\Lambda hyperons in ppNe collisions at sNN\sqrt{s_{NN}}=68.4 GeV with the LHCb detector

A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$=68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,$$ Furthermore, the results are shown as a function of the Feynman $x$ variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements.A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$ hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$ = 68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,.$$ Furthermore, the results are shown as a function of the Feynman~$x$~variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements

Transverse polarization measurement of Λ\Lambda hyperons in ppNe collisions at sNN\sqrt{s_{NN}} = 68.4 GeV with the LHCb detector

International audienceA measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$ hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$ = 68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$$$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,.$$ Furthermore, the results are shown as a function of the Feynman~$x$~variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements

Transverse polarization measurement of Λ\Lambda hyperons in ppNe collisions at sNN\sqrt{s_{NN}} = 68.4 GeV with the LHCb detector

International audienceA measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$ hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$ = 68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$$$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,.$$ Furthermore, the results are shown as a function of the Feynman~$x$~variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements