Plasticity and lineage commitment of individual T1 cells are determined by stable T-bet expression quantities.

T helper 1 (T1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection.

A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses.

The pleiotropic alarmin interleukin-33 (IL-33) drives type 1, type 2 and regulatory T-cell responses via its receptor ST2. Subset-specific differences in ST2 expression intensity and dynamics suggest that transcriptional regulation is key in orchestrating the context-dependent activity of IL-33-ST2 signaling in T-cell immunity. Here, we identify a previously unrecognized alternative promoter in mice and humans that is located far upstream of the curated ST2-coding gene and drives ST2 expression in type 1 immunity.

NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs).

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1 CD8 T cells in chronic viral infection.

T cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8 T cells (CD8SL) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8SL as well as for virus control.

Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth.

Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined.

Menstrual blood-derived mesenchymal stromal cells efficiently ameliorate experimental autoimmune encephalomyelitis by inhibiting T cell activation in mice.

Background: Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE).

Vaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection.

Chronic viral infections subvert protective B cell immunity. An early type I interferon (IFN-I)-driven bias to short-lived plasmablast differentiation leads to clonal deletion, so-called "decimation," of antiviral memory B cells. Therefore, prophylactic countermeasures against decimation remain an unmet need.

Th2 cells lacking T-bet suppress naive and memory T cell responses via IL-10.

Exacerbated immune responses and loss of self-tolerance lead to the development of autoimmunity and immunopathology. Novel therapies to target autoreactive T cells are still needed. Here, we report that Th2-polarized T cells lacking the transcription factor T-bet harbor strong immunomodulatory potential and suppress antigen-specific CD8 T cells via IL-10.

Series of Tetravalent Actinide Amidinates: Structure Determination and Bonding Analysis.

Two series of isostructural tetravalent actinide amidinates [AnX(()-PEBA)] (An = Th, U, Np; X = Cl, N) bearing the chiral (,)-,'-bis(1-phenylethyl)benzamidinate (()-PEBA) ligand have been synthesized and thoroughly characterized in solid and in solution. This study expands the already reported tetravalent neptunium complexes to the lighter actinides thorium and uranium. Furthermore, a rare Ce(IV) amidinate [CeCl(()-PEBA)] was synthesized to compare its properties to those of the analogous tetravalent actinide complexes.

Enantiomerically Pure Tetravalent Neptunium Amidinates: Synthesis and Characterization.

The synthesis of a tetravalent neptunium amidinate [NpCl((S)-PEBA) ] (1) ((S)-PEBA=(S,S)-N,N'-bis-(1-phenylethyl)-benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)-PEBA) ] (X=F (2), Br (3), N (4)) have shown that the chirality-at-metal is preserved for all compounds in the solid state.

Memory CD8 T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals.

Memory CD8 cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells.

Signatures of Indistinguishability in Bosonic Many-Body Dynamics.

The dynamics of bosons in generic multimode systems, such as Bose-Hubbard models, are not only determined by interactions among the particles, but also by their mutual indistinguishability manifested in many-particle interference. We introduce a measure of indistinguishability for Fock states of bosons whose mutual distinguishability is controlled by an internal degree of freedom. We demonstrate how this measure emerges both in the noninteracting and interacting evolution of observables.

Application of F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals.

A simple, rapid, and selective quantitative nuclear magnetic resonance spectroscopic method was evaluated for the determination of the content of fluorinated pharmaceuticals. F NMR spectra were either obtained in dimethylsulfoxide- or aqueous buffer, using trifluoroacetic acid as internal standard. Quantification of 13 fluorine-containing pharmaceuticals spanning various pharmacological classes was accomplished using the proposed method.

Synthesis and post-synthetic modification of amine-, alkyne-, azide- and nitro-functionalized metal-organic frameworks based on DUT-5.

Functionalized 4,4'-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal-organic frameworks and mixed-linker metal-organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials.

Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus.

Background: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy.

Methods: The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial.

Effect of nanoparticulate bioactive glass particles on bioactivity and cytocompatibility of poly(3-hydroxybutyrate) composites.

This work investigated the effect of adding nanoparticulate (29 nm) bioactive glass particles on the bioactivity, degradation and in vitro cytocompatibility of poly(3-hydroxybutyrate) (P(3HB)) composites/nano-sized bioactive glass (n-BG). Two different concentrations (10 and 20 wt %) of nanoscale bioactive glass particles of 45S5 Bioglass composition were used to prepare composite films. Several techniques (Raman spectroscopy, scanning electron microscopy, atomic force microscopy, energy dispersive X-ray) were used to monitor their surface and bioreactivity over a 45-day period of immersion in simulated body fluid (SBF).

Comparative assessment of time-related bioactive glass and calcium hydroxide effects on mechanical properties of human root dentin.

Suspensions of micro- or nanoparticulate SiO(2)-Na(2)O-CaO-P(2)O(5) bioactive glasses could potentially be used as dressings in traumatized front teeth with open apices as an alternative to Ca(OH)(2). These materials have a disinfecting capacity similar to Ca(OH)(2), but bear the advantage of bioactivity. However, because bioactive glasses initially act as alkaline biocides just as Ca(OH)(2) does, they may also negatively affect mechanical dentin properties over time.

In vivo and in vitro evaluation of flexible, cottonwool-like nanocomposites as bone substitute material for complex defects.

The easy clinical handling and applicability of biomaterials has become a focus of materials research due to rapidly increasing time and cost pressures in the public health sector. The present study assesses the in vitro and in vivo performance of a flexible, mouldable, cottonwool-like nanocomposite based on poly(lactide-co-glycolide) and amorphous tricalcium phosphate nanoparticles (PLGA/TCP 60:40). Immersion in simulated body fluid showed exceptional in vitro bioactivity for TCP-containing fibres (mass gain: 18%, 2 days, HAp deposition).

Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites.

This study compares the effects of introducing micro (m-BG) and nanoscale (n-BG) bioactive glass particles on the various properties (thermal, mechanical and microstructural) of poly(3hydroxybutyrate) (P(3HB))/bioactive glass composite systems. P(3HB)/bioactive glass composite films with three different concentrations of m-BG and n-BG (10, 20 and 30 wt%, respectively) were prepared by a solvent casting technique. The addition of n-BG particles had a significant stiffening effect on the composites, modulus when compared with m-BG.

Cotton wool-like nanocomposite biomaterials prepared by electrospinning: in vitro bioactivity and osteogenic differentiation of human mesenchymal stem cells.

The present study evaluates the in vitro biomedical performance of an electrospun, flexible, and cotton wool-like poly(lactide-co-glycolide) (PLGA)/amorphous tricalcium phosphate (ATCP) nanocomposite. Experiments on in vitro biomineralization, applicability in model defects and a cell culture study with human mesenchymal stem cells (hMSC) allowed assessing the application of the material for potential use as a bone graft. Scaffolds with different flame made ATCP nanoparticle loadings were prepared by electrospinning of a PLGA-based composite.

Remineralization of human dentin using ultrafine bioactive glass particles.

Bioactive glass nanoparticles synthesized by flame spray synthesis were tested for their remineralization capabilities in vitro. After artificial demineralization with EDTA, human dentin was treated with 20-50nm size bioactive glass nanoparticles or a micrometer-sized, commercial reference material (PerioGlas) for up to 30 days. The degree of remineralization was measured using quantitative gravimetric methods (thermogravimetry, elemental analysis) and element-sensitive scanning electron microscopy imaging to detect new mineral precipitated on or within the demineralized tooth matrix.

Inorganic nanoparticles for transfection of mammalian cells and removal of viruses from aqueous solutions.

Owing to their small size, synthetic nanoparticles show unprecedented biophysical and biochemical properties which may foster novel advances in life-science research. Using flame-spray synthesis technology we have produced non-coated aluminum-, calcium-, cerium-, and zirconium-derived inorganic metal oxide nanoparticles which not only exhibit high affinity for nucleic acids, but can sequester such compounds from aqueous solution. This non-covalent DNA-binding capacity was successfully used to transiently transfect a variety of mammalian cells including human, reaching transfection efficiencies which compared favorably with classic calcium phosphate precipitation (CaP) procedures and lipofection.

Comparison of amorphous TCP nanoparticles to micron-sized alpha-TCP as starting materials for calcium phosphate cements.

The development of degradable bone cements with a mineral composition similar to natural bone was investigated using highly reactive calcium phosphate phases as starting materials. Mixtures of XRD-amorphous, glassy tricalcium phosphate (amorphous-TCP) nanoparticles of 25-60 nm size and micron sized, milled alpha-TCP were set by hydration with sodium phosphate buffer and investigated for possible application as single component calcium phosphate cements (CPCs). Isothermal calorimetry allowed a precise tracking of the setting process.

In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility.

Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0-30 ppm nanoparticles (microg g(-1)) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos.

Glass and bioglass nanopowders by flame synthesis.

The preparation of amorphous nanopowders by flame synthesis opens access to common soda-lime, metal-doped glasses or bioglasses in the range of 20-80 nm and offers an alternative to conventional wet-phase preparation, solid state reactions or melting.