Development of an oral protein subunit COVID-19 vaccine to induce mucosal and systemic immune response

It is widely recognized that mucosal immunization is the most efficient route of delivery to offer protective immunity. Oral administration can boost the economic value of vaccines, make needle-free delivery possible, and allow for safe and convenient self-administration. Despite these critical advantages, there are very few oral or nasal COVID-19 vaccine in development, and none on the market. The main challenge for an efficacious vaccine administered orally is the need for an efficient antigen delivery system into the mucosa. VaxForm has developed a technology that consists of co-adsorbing antigen(s) and a C-type lectin (CTL) receptor agonist to an aluminum delivery particle and encapsulating the vaccine with an enteric polymer to protect it from the stomach acidic environment and enhance stability. Once in the intestines, the protective polymer dissolves, and the CTL agonist targets the microfold (M) cells in the gut associated lymphoid tissues (GALT), allowing efficient delivery of the antigens adsorbed to aluminum particle Please click Download on the upper right corner to see the full abstract

Spring Water Geochemistry: A Geothermal Exploration Tool in the Rhenohercynian Fold-and-Thrust Belt in Belgium

peer reviewedSpring water geochemistry is applied here to evaluate the geothermal potential in Rhenohercynian fold and thrust belt around the deepest borehole in Belgium (Havelange borehole: 5648 m MD). Fifty springs and (few) wells around Havelange borehole were chosen according to a multicriteria approach including the hydrothermal source of “Chaudfontaine” (T ≈ 36 ◦C) taken as a reference for the area. The waters sampled, except Chaudfontaine present an in-situ T range of 3.66–14.04 ◦C (mean 9.83 ◦C) and a TDS (dry residue) salinity range of 46–498 mg/L. The processing methods applied to the results are: hierarchical clustering, Piper and Stiff diagrams, TIS, heat map, boxplots, and geothermometry. Seven clusters are found and allow us to define three main water types. The first type, locally called “pouhon”, is rich in Fe and Mn. The second type contains an interesting concentration of the geothermal indicators: Li, Sr, Rb. Chaudfontaine and Moressée (≈5 km East from the borehole) belong to this group. This last locality is identified as a geothermal target for further investigations. The third group represents superficial waters with frequently high NO3 concentration. The application of conventional geothermometers in this context indicates very different reservoir temperatures. The field of applications of these geothermometers need to be review in these geological conditions.MEE

Results of a Precrash Application Based on Laser Scanner and Short-Range Radars

International audienceIn this paper, we present a vehicle safety application based on data gathered by a laser scanner and two short-range radars that recognize unavoidable collisions with stationary objects before they take place to trigger restraint systems. Two different software modules that perform the processing of raw data and deliver a description of the vehicle's environment are compared. A comprehensive experimental evaluation based on relevant crash and noncrash scenarios is presented

Maternally deposited germline piRNAs silence the tirant

International audienceTransposable elements (TEs), whose propagation can result in severe damage to the host genome, are silenced in the animal gonad by Piwi-interacting RNAs (piRNAs). piRNAs produced in the ovaries are deposited in the embryonic germline and initiate TE repression in the germline progeny. Whether the maternally transmitted piRNAs play a role in the silencing of somatic TEs is however unknown. Here we show that maternally transmitted piRNAs from the tirant retrotransposon in Drosophila are required for the somatic silencing of the TE and correlate with an increase in histone H3K9 trimethylation an active tirant copy

Mass Spectrometry-based Absolute Quantification of 20S Proteasome Status for Controlled Ex-vivo Expansion of Human Adipose-derived Mesenchymal Stromal/Stem Cells

International audienceIn Brief 20S proteasomes are very heterogeneous protein complexes involved in many cellular processes. In the present study, we combined an MRM-based assay with the production and purification of entire SILAC labelled pro-teasome to monitor absolute quantities of the different 20S proteasome subtypes in various human cells and tissues. This method applied to adipocyte-derived stem cells (ADSCs) amplified under various conditions highlights an increased expression of immunoproteasome when this type of cell is primed with IFN␥ or amplified in a 20% O 2 environment. Graphical Abstract Highlights • Design of an MRM assay to determine the absolute quantity and stoichiometry of ubiquitous and tissue-specific human 20S proteasome subtypes. • Use of purified isotopically labelled 20S proteasome as internal standard for accurate quantification. • Variation in the expression of immunoproteasome in adipocyte-derived stem cells (ADSCs) grown under different O 2 levels might be causal for change in cells differentiation capacity. • The status of 20S proteasome during ADSCs expansion might constitute an additional relevant quality control parameter to contribute to predict, among other quality markers, their therapeutic capacity

PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ

PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28γ, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28γ. Its recruitment to proteasome-containing complexes depends on PA28γ and its expression increases the association of PA28γ with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28γ-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28γ in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28γ interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28γ in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus

Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy

textabstractSpinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 messenger ribonucleic acid (mRNA) is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail. In contrast, how much SMN protein is produced at different developmental time points and in different tissues remains under-characterized. In this study, we addressed this issue by determining SMN protein expression levels at three developmental time points across six different mouse tissues and in two distinct mouse models of SMA ('severe' Taiwanese and 'intermediate' Smn2B/mice). We found that, in healthy control mice, SMN protein expression was significantly influenced by both age and tissue type.When comparing mouse models of SMA, we found that, despite being transcribed from genetically different alleles, control SMN levels were relatively similar. In contrast, the degree of SMN depletion between tissues in SMA varied substantially over time and between the two models. These findings offer an explanation for the differential vulnerability of tissues and organs observed in SMA and further our understanding of the systemic and temporal requirements for SMN with direct relevance for developing effective therapies for SMA