Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study.

This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg.

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers.

Modern humans have populated Europe for more than 45,000 years. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago.

Dynamics of small unilamellar vesicles.

In this paper, we investigate the dynamics of small unilamellar vesicles with the aid of neutron spin-echo spectroscopy. The purpose of this investigation is twofold. On the one hand, we investigate the influence of solubilised cosurfactant on the dynamics of the vesicle's surfactant bilayer.

Potential and limitations of microscopy and Raman spectroscopy for live-cell analysis of 3D cell cultures.

Today highly complex 3D cell culture formats that closely mimic the in vivo situation are increasingly available. Despite their wide use, the development of analytical methods and tools that can work within the depth of 3D-tissue constructs lags behind. In order to get the most information from a 3D cell sample, adequate and reliable assays are required.

Nanocasting hierarchical carbide-derived carbons in nanostructured opal assemblies for high-performance cathodes in lithium-sulfur batteries.

Silica nanospheres are used as templates for the generation of carbide-derived carbons with monodisperse spherical mesopores (d=20-40 nm) and microporous walls. The nanocasting approach with a polycarbosilane precursor and subsequent pyrolysis, followed by silica template removal and chlorine treatment, results in carbide-derived carbons DUT-86 (DUT=Dresden University of Technology) with remarkable textural characteristics, monodisperse, spherical mesopores tunable in diameter, and very high pore volumes up to 5.0 cm3 g(-1).

Nanoporous and highly active silicon carbide supported CeO₂-catalysts for the methane oxidation reaction.

CeOx @SiO2 nanoparticles are used for the first time for the generation of porous SiC materials with tailored pore diameter in the mesopore range containing encapsulated and catalytically active CeO2 nanoparticles. The nanocasting approach with a preceramic polymer and subsequent pyrolysis is performed at 1300 °C, selective leaching of the siliceous part results in CeOx /SiC catalysts with remarkable characteristics like monodisperse, spherical pores and specific surface areas of up to 438 m(2) ·g(-1) . Porous SiC materials are promising supports for high temperature applications.

Integrating macrophages into organotypic co-cultures: a 3D in vitro model to study tumor-associated macrophages.

Tumor progression is controlled by signals from cellular and extra-cellular microenvironment including stromal cells and the extracellular matrix. Consequently, three-dimensional in vitro tumor models are essential to study the interaction of tumor cells with their microenvironment appropriately in a biologically relevant manner. We have previously used organotypic co-cultures to analyze the malignant growth of human squamous cell carcinoma (SCC) cell lines on a stromal equivalent in vitro.

Preparation and application of cellular and nanoporous carbides.

A tutorial review on cellular as well as nanoporous carbides covering their structure, synthesis and potential applications. Especially new carbide materials with a hierarchical pore structure are in focus. As a central theme silicon carbide based materials are picked out, but also titanium, tungsten and boron carbides, as well as carbide-derived carbons, are part of this review.

In macrophages, caspase-1 activation by SopE and the type III secretion system-1 of S. typhimurium can proceed in the absence of flagellin.

The innate immune system is of vital importance for protection against infectious pathogens. Inflammasome mediated caspase-1 activation and subsequent release of pro-inflammatory cytokines like IL-1beta and IL-18 is an important arm of the innate immune system. Salmonella enterica subspecies 1 serovar Typhimurium (S.

The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation.

In the healthy intestinal mucosa, homeostasis between the immune system and commensal microflora prevents detrimental inflammatory responses. Infection with acute enteropathogens such as Salmonella enterica serovar Typhimurium disturbs this homeostasis and triggers inflammation, but the underlying mechanisms are poorly understood. We found that bacterial delivery or ectopic expression of the S.

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: a contribution to understand colloidal protein stabilisation.

The development of liquid therapeutic protein drugs imposes the presence of specific stabilisation agents to prevent protein degradation in order to reach shelf-lives of at least 2 years for drugs stored at 2-8 degrees C. Non-ionic detergents are used to avoid protein adsorption and the formation of protein aggregates. Depending on the protein and excipient (detergent) used the stabilisation effect is quite different and cannot be predicted up to now.

Insights into protein-polysorbate interactions analysed by means of isothermal titration and differential scanning calorimetry.

Therapeutic proteins formulated as liquid solutions at high protein concentration are very sensitive to chemical and physical degradation. Especially avoiding the formation of protein aggregates is very crucial for product quality. In order to stabilize the colloidal properties of protein therapeutics various excipient are used.

Testosterone supplementation for hypogonadal men by the nasal route.

Although multiple forms of testosterone replacement therapy are available to treat hypogonadism, none is ideal. This article reports on the pharmacokinetics of an innovative nasal formulation of testosterone in hypogonadal men. The first study was undertaken in eight men with a baseline total testosterone (TT) of 130.

The cytotoxic necrotizing factors from Yersinia pseudotuberculosis and from Escherichia coli bind to different cellular receptors but take the same route to the cytosol.

The cytotoxic necrotizing factors CNF1 and CNF2 produced by pathogenic Escherichia coli strains and CNF(Y) of Yersinia pseudotuberculosis constitutively activate small GTPases of the Rho family. They deamidate a glutamine (Gln63 in RhoA), which is crucial for GTP hydrolysis. CNF1 and CNF(Y) exhibit 61% identity on the amino acid level, with equal distribution over the whole molecule.

Change in substrate specificity of cytotoxic necrotizing factor unmasks proteasome-independent down-regulation of constitutively active RhoA.

Cytotoxic necrotizing factors CNF1 and CNF2 are produced by pathogenic Escherichia coli strains. They constitutively activate small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. Recently, a novel CNF (CNF(Y)) encompassing 65% identity to CNF1 has been identified in Yersinia pseudotuberculosis.

The Yersinia pseudotuberculosis cytotoxic necrotizing factor (CNFY) selectively activates RhoA.

The cytotoxic necrotizing factors (CNF)1 and CNF2 from pathogenic Escherichia coli strains activate RhoA, Rac1, and Cdc42 by deamidation of Gln63 (RhoA) or Gln61 (Rac and Cdc42). Recently, a novel cytotoxic necrotizing factor termed CNFY was identified in Yersinia pseudotuberculosis strains (Lockman, H. A.

The C terminus of YopT is crucial for activity and the N terminus is crucial for substrate binding.

Recently, it was shown that Yersinia outer protein T (YopT) belongs to a new family of cysteine proteases containing invariant C, H, and D residues that are crucial for its activity. YopT cleaves RhoA, Rac, and Cdc42 at their C termini, thereby releasing them from the membrane. Moreover, YopT inhibits the Rho-rhotekin and Rho-guanine nucleotide dissociation inhibitor interactions.

Survey of adverse drug reactions on a pediatric ward: a strategy for early and detailed detection.

Objective: Adverse drug reactions (ADRs) occur frequently in children. However, the exact incidence of ADRs is unknown. Therefore, we studied ADRs in 1 ward and assessed whether a general approach, eg, by a computerized monitoring system, to detect ADRs in children is feasible and likely to yield a higher rate of early detected ADRs.