IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this ...study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients.
IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides.
IL-9 was overexpressed in RA synovial tissues and correlated with the degree of histological organization of B and T cells in ectopic lymphoid structures. The majority of IL-9-producing cells were identified as CD3(+) cells. Increased mRNA and protein expression of IL-9R, IL-4, TSLP and TGF-β was also observed in RA synovial tissue. Blood peripheral Th9 cells were expanded by citrullinated peptides.
These results indicate that Th9 cells and IL-9 were frequently detected in peripheral blood mononuclear cells and synovia of RA patients. A possible pathogenic role for Th9 in RA is discussed.
By inspection of the predicted proteome of the fungus Myceliophthora thermophila C1 for vanillyl-alcohol oxidase (VAO)-type flavoprotein oxidases, a putative oligosaccharide oxidase was identified. ...By homologous expression and subsequent purification, the respective protein could be obtained. The protein was found to contain a bicovalently bound FAD cofactor. By screening a large number of carbohydrates, several mono- and oligosaccharides could be identified as substrates. The enzyme exhibits a strong substrate preference toward xylooligosaccharides; hence it is named xylooligosaccharide oxidase (XylO). Chemical analyses of the product formed upon oxidation of xylobiose revealed that the oxidation occurs at C1, yielding xylobionate as product. By elucidation of several XylO crystal structures (in complex with a substrate mimic, xylose, and xylobiose), the residues that tune the unique substrate specificity and regioselectivity could be identified. The discovery of this novel oligosaccharide oxidase reveals that the VAO-type flavoprotein family harbors oxidases tuned for specific oligosaccharides. The unique substrate profile of XylO hints at a role in the degradation of xylan-derived oligosaccharides by the fungus M. thermophila C1.
Heterogeneities in structure and polarization have been employed to enhance the energy storage properties of ferroelectric films. The presence of nonpolar phases, however, weakens the net ...polarization. Here, we achieve a slush-like polar state with fine domains of different ferroelectric polar phases by narrowing the large combinatorial space of likely candidates using machine learning methods. The formation of the slush-like polar state at the nanoscale in cation-doped BaTiO3 films is simulated by phase field simulation and confirmed by aberration-corrected scanning transmission electron microscopy. The large polarization and the delayed polarization saturation lead to greatly enhanced energy density of 80 J/cm3 and transfer efficiency of 85% over a wide temperature range. Such a data-driven design recipe for a slush-like polar state is generally applicable to quickly optimize functionalities of ferroelectric materials.
We report on the mechanism for hydrogen-induced topotactic phase transitions in perovskite (PV) oxides using La0.7Sr0.3MnO3 as a prototypical example. Hydrogenation starts with lattice expansion ...confirmed by X-ray diffraction (XRD). The strain- and oxygen-vacancy-mediated electron-phonon coupling in turn produces electronic structure changes that manifest through the appearance of a metal insulator transition accompanied by a sharp increase in resistivity. The ordering of initially randomly distributed oxygen vacancies produces a PV to brownmillerite phase (La0.7Sr0.3MnO2.5) transition. This phase transformation proceeds by the intercalation of oxygen vacancy planes confirmed by in situ XRD and neutron reflectometry (NR) measurements. Despite the prevailing picture that hydrogenation occurs by reaction with lattice oxygen, NR results are not consistent with deuterium (hydrogen) presence in the La0.7Sr0.3MnO3 lattice at steady state. The film can reach a highly oxygen-deficient La0.7Sr0.3MnO2.1 metastable state that is reversible to the as-grown composition simply by annealing in air. Theoretical calculations confirm that hydrogenation-induced oxygen vacancy formation is energetically favorable in La0.7Sr0.3MnO3. The hydrogenation-driven changes of the oxygen sublattice periodicity and the electrical and magnetic properties similar to interface effects induced by oxygen-deficient cap layers persist despite hydrogen not being present in the lattice.
Objective
To investigate microvascular alterations in an experimental model of metabolic syndrome induced by a high‐fat diet (HFD) associated with salt supplementation (0.5% NaCl).
Design and Methods
...Wistar Kyoto rats were fed standard chow (control group, CONT) or HFD for 20 weeks. The functional capillary density (FCD) was assessed using intravital fluorescence videomicroscopy.
Results
The HFD group presented a higher systolic blood pressure, plasma glucose and insulin levels, total and LDL‐cholesterol levels, triglycerides, and visceral and epididymal fat when compared with the CONT group. When compared with the CONT group, the HFD group showed a lower FCD in the skeletal muscle (P < 0.05) but not in the skin (P > 0.05). The HFD group also had a lower capillary‐to‐fiber ratio in the skeletal muscle (P < 0.01). The capillary volume density‐to‐fiber volume density ratio in the left ventricle of the HFD was also reduced (P < 0.01). Finally, rats fed with HFD showed ventricular hypertrophy and increased cardiomyocyte diameter (P < 0.01).
Conclusions
The long‐term administration of a HFD associated with salt supplementation to rats generates an experimental model of metabolic syndrome characterized by central body fat deposition, insulin resistance, glucose intolerance, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, cardiac remodeling, and rarefaction of the microcirculation in the heart and skeletal muscle.
Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s and ...vaccination has proved highly successful in reducing the disease burden, the development of the carrier state and the HB-related morbidity and mortality in the countries where vaccination has been implemented.
Neutralizing (protective) antibodies (anti-HBs) induced by vaccination are targeted largely towards the amino acid hydrophilic region, referred to as the common a determinant which is present on the outer protein coat or surface antigen (HBsAg), spanning amino acids 124-149. This provides protection against all HBV genotypes (from A to H) and is responsible for the broad immunity afforded by hepatitis B vaccination. Thus, alterations of residues within this region of the surface antigen may determine conformational changes that can allow replication of the mutated HBV in vaccinated people.
An important mutation in the surface antigen region was identified in Italy some 25 years ago in infants born to HBsAg carrier mothers who developed breakthrough infections despite having received HBIG and vaccine at birth. This virus had a point mutation from guanosine to adenosine at nucleotide position 587, resulting in aa substitution from glycine (G) to arginine (R) at position 145 in the a determinant. Since the G145R substitution alters the projecting loop (aa 139-147) of the a determinant, the neutralizing antibodies induced by vaccination are no longer able to recognize the mutated epitope. Beside G145R, other S-gene mutations potentially able to evade neutralizing anti-HBs and infect vaccinated people have been described worldwide.
In addition, the emergence of Pol mutants associated with resistance to treatment with nucleos(t)ide analogues can select viruses with crucial changes in the overlapping S-gene, potentially able to alter the S protein immunoreactivity. Thus such mutants have the potential to infect both naïve and immunized people, negatively affecting the efficacy of both the antiviral treatment and the vaccination programs.
Despite concern, at present the overall impact of vaccine escapes mutants seems to be low and they do not pose a public health threat or a need to modify the established hepatitis B vaccination programs. The development of novel NAs with a high barrier to resistance is warranted.
Modifying the properties of graphene has gained wide interest for a plethora of potential applications, including spintronics. One approach has demonstrated that proton irradiation can induce ...ferromagnetism in graphene as well as in graphite. However, little is known about how the protons interact with graphene, the mechanism that creates the ferromagnetism, or whether the protons remain in the graphene. Here we report an investigation, broadly relevant to graphitic carbon, using low-energy (360–2000 eV) ions of hydrogen, deuterium, and helium implanted into multilayer epitaxial graphene. Complementary x-ray and neutron reflectivity demonstrate that essentially all of the implanted hydrogen remains chemisorbed in graphene. In situ x-ray diffraction reveals significantly different rates of interlayer expansion of the multilayer graphene. Analysis of these data demonstrates that the interlayer expansion arises entirely from the interstitials created by the ions and not from hydrogen that remains in the graphene. The results also establish a quantitative measure of the layer expansion due to carbon interstitials. Magnetometry and x-ray diffraction studies show that the magnetic moment relates to the amount of interstitial carbon rather than the amount of hydrogen, demonstrating that the induced room-temperature ferromagnetism arises directly from the disrupted bonding of the carbon lattice.
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In contrast to perovskites that share only common corners of cation‐occupied octahedra, binary‐oxides in addition share edges and faces increasing the versatility for tuning the properties and ...functionality of reduced dimensionality systems of strongly correlated oxides. This approach for tuning the electronic structure is based on the ability of X‐ray spectroscopy methods to monitor the creation and transformation of occupied and unoccupied electronic states produced by interface coupling and lattice distortions. X‐ray diffraction reveals a new range of structural metastability in (TiO2)m/(VO2)m/TiO2(001) superlattices with m = 1, 3, 5, 20, 40, and electrical transport measurements show metal insulator transition (MIT) behavior typically associated with presence of high oxygen vacancy concentrations. However, X‐ray absorption spectroscopy (XAS) at the Ti and V L3,2‐edge and resonant inelastic X‐ray scattering (RIXS) at the Ti and V L3‐edge show no excitations characteristic of oxygen vacancy induced valance change in V and negligible intensities in Ti RIXS. The unexpected absence of oxygen vacancy related states in the X‐ray spectroscopy data suggests that superlattice fabrication is capable of suppressing oxygen vacancy formation while still affording a wide tunability range of the MIT. Achieving a wide range of MIT tunability while reducing or eliminating oxygen vacancies that are detrimental to electrical properties is highly desirable for technological applications of strongly correlated oxides.
It is reported here that superlattices consisting of alternating VO2 and TiO2 epitaxial layers provide a new metastability range with dramatically altered VO2 properties. Electrical transport and X‐ray spectroscopy measurements reveal that the superlattice properties are governed by multiple strain mechanisms and despite unexpectedly low oxygen vacancy concentration provide a wide tunability range of the VO2 metal insulator transition.
We report on the mechanism for hydrogen-induced topotactic phase transitions in perovskite (PV) oxides using La
Sr
MnO
as a prototypical example. Hydrogenation starts with lattice expansion confirmed ...by X-ray diffraction (XRD). The strain- and oxygen-vacancy-mediated electron-phonon coupling in turn produces electronic structure changes that manifest through the appearance of a metal insulator transition accompanied by a sharp increase in resistivity. The ordering of initially randomly distributed oxygen vacancies produces a PV to brownmillerite phase (La
Sr
MnO
) transition. This phase transformation proceeds by the intercalation of oxygen vacancy planes confirmed by in situ XRD and neutron reflectometry (NR) measurements. Despite the prevailing picture that hydrogenation occurs by reaction with lattice oxygen, NR results are not consistent with deuterium (hydrogen) presence in the La
Sr
MnO
lattice at steady state. The film can reach a highly oxygen-deficient La
Sr
MnO
metastable state that is reversible to the as-grown composition simply by annealing in air. Theoretical calculations confirm that hydrogenation-induced oxygen vacancy formation is energetically favorable in La
Sr
MnO
. The hydrogenation-driven changes of the oxygen sublattice periodicity and the electrical and magnetic properties similar to interface effects induced by oxygen-deficient cap layers persist despite hydrogen not being present in the lattice.
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