PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed.     

Validation of the performance of a GMO multiplex screening assay based on microarray detection

A new screening method for the detection and identification of GMO, based on the use of multiplex PCR followed by microarray, has been developed and is presented. The technology is based on the identification of quite ubiquitous GMO genetic target elements first amplified by PCR, followed by direct hybridisation of the amplicons on a predefined microarray (DualChip^® GMO, Eppendorf, Germany). The validation was performed within the framework of a European project (Co-Extra, contract no 007158) and in collaboration with 12 laboratories specialised in GMO detection. The present study reports the strategy and the results of an ISO complying validation of the method carried out through an inter-laboratory study. Sets of blind samples were provided consisting of DNA reference materials covering all the elements detectable by specific probes present on the array. The GMO concentrations varied from 1% down to 0.045%. In addition, a mixture of two GMO events (0.1% RRS diluted in 100% TOPAS19/2) was incorporated in the study to test the robustness of the assay in extreme conditions. Data were processed according to ISO 5725 standard. The method was evaluated with predefined performance criteria with respect to the EC CRL method acceptance criteria. The overall method performance met the acceptance criteria; in particular, the results showed that the method is suitable for the detection of the different target elements at 0.1% concentration of GMO with a 95% accuracy rate. This collaborative trial showed that the method can be considered as fit for the purpose of screening with respect to its intra- and inter-laboratory accuracy. The results demonstrated the validity of combining multiplex PCR with array detection as provided by the DualChip^® GMO (Eppendorf, Germany) for the screening of GMO. The results showed that the technology is robust, practical and suitable as a screening tool.     

Particle atomic layer deposition of alumina for sintering yttria-stabilized cubic zirconia

The addition of aluminum oxide (Al₂O₃) as a sintering aid to yttria-stabilized zirconia (YSZ) reduces the required densification temperature. Sintering aids are incorporated using a number of processes which can lead to ambiguity when determining the effect of the sintering aid on the densification mechanism. In this study, a novel method for sintering aid addition, Particle Atomic Layer Deposition (ALD), was used to deposit an amorphous Al₂O₃ thin film on YSZ particles. Transmission electron microscopy confirmed the deposition of conformal Al₂O₃ thin films on the surface of the YSZ particles. The addition of Al₂O₃ to YSZ reduced the temperature at which densification began by ~75°C, and 2.2 wt% Al₂O₃ addition resulted in a minimum activation energy for the intermediate stage of densification. This concentration is well in excess of the solubility limit of Al₂O₃ in YSZ, showing that Al₂O₃ does not enhance the densification of YSZ solely by dissolving into the YSZ lattice and activating volume diffusion. The addition of 0.7 wt% Al₂O₃ with one Particle ALD cycle enhanced the ionic conductivity of YSZ by 23% after sintering at 1350°C for 2 hours, demonstrating that dense parts with high oxygen ion conductivities can be produced after sintering at reduced temperatures. One Particle ALD cycle is a fast, easily scaled-up process that eliminates the use of solvents and has substantial cost/performance advantages over conventional processing.     

New Paradigm in NKT Cell Antigens: MCS-0208 (2-(Hydroxymethyl)phenylthio-phytoceramide) – an Aryl-Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells

Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS-0208, an unprecedented arylthioether-phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT cells. This arylsphingolipid analog has a simple phenyl group containing a single hydroxyl substituent as a surrogate of the sugar ring. The phenylthioether structure contrasts with α-galactosylceramide ( 1 ), the prototypical glycolipid used to induce iNKT cell stimulation, where the galactose 2’-OH and 3’-OH substituents are accepted as the minimal footprint and considered critical for NKT T cell receptor (TCR) recognition. A computational study supports the recognition of aromatic compound by the CD1d and TCR proteins as radically new structures for NKT cell stimulation.     

Evaluation of dynamic modulus measurement for C/C-SiC composites at different temperatures

The determination of elastic properties at application temperature is fundamental for the design of fibre reinforced ceramic composite components. An attractive method to characterize the flexural modulus at room and high temperature under specific atmosphere is the nondestructive Resonant Frequency Damping Analysis (RFDA). The objective of this paper was to evaluate and validate the modulus measurement via RFDA for orthotropic C/C-SiC composites at the application temperature. At room temperature flexural moduli of C/C-SiC with 0/90° reinforcement were measured under quasi-static 4-point bending loads and compared with dynamic moduli measured via RFDA longitudinally to fibre direction. The dynamic modulus of C/C-SiC was then measured via RFDA up to 1250°C under flowing inert gas and showed an increase with temperature which fitted with literature values. The measured fundamental frequencies were finally compared to those resulting from numerical modal analyses. Dynamic and quasi-static flexural moduli are comparable and the numerical analyses proved that bending modes are correctly modeled by means of dynamic modulus measured via RFDA. The nondestructive RFDA as well as the numerical modeling approach are suitable for evaluation of C/C-SiC and may be transferred to other fibre reinforced ceramic composite materials.     

Partial Sperm beta1 Integrin Subunit Deletion Proves Its Involvement in Mouse Gamete Adhesion/Fusion

We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion in vitro. Here we report the conditional knockdown of the sperm Itgb1 gene. It induced a drastic failure of sperm fusogenic ability with sperm accumulation in the perivitelline space of in vitro inseminated oocytes deleted or not for the Itgb1 gene. These data demonstrate that sperm, but not oocyte, beta1 integrin subunit is involved in gamete adhesion/fusion. Curiously, knockdown males were fertile in vivo probably because of the incomplete Cre-mediated deletion of the sperm Itgb1 floxed gene. Indeed, this was shown by Western blot analysis and confirmed by both the viability and litter size of pups obtained by mating partially sperm Itgb1 deleted males with females producing completely deleted Itgb1 oocytes. Because of the total peri-implantation lethality of Itgb1 deletion in mice, we assume that sperm that escaped the Itgb1 excision seemed to be preferentially used to fertilize in vivo. Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary.     

Nano‐Architectured Composite Anode Enabling Long‐Term Cycling Stability for High‐Capacity Lithium‐Ion Batteries

Failure mechanisms associated with silicon‐based anodes are limiting the implementation of high‐capacity lithium‐ion batteries. Understanding the aging mechanism that deteriorates the anode performance and introducing novel‐architectured composites offer new possibilities for improving the functionality of the electrodes. Here, the characterization of nano‐architectured composite anode composed of active amorphous silicon domains (a‐Si, 20 nm) and crystalline iron disilicide (c‐FeSi₂, 5–15 nm) alloyed particles dispersed in a graphite matrix is reported. This unique hierarchical architecture yields long‐term mechanical, structural, and cycling stability. Using advanced electron microscopy techniques, the nanoscale morphology and chemical evolution of the active particles upon lithiation/delithiation are investigated. Due to the volumetric variations of Si during lithiation/delithiation, the morphology of the a‐Si/c‐FeSi₂ alloy evolves from a core‐shell to a tree‐branch type structure, wherein the continuous network of the active a‐Si remains intact yielding capacity retention of 70% after 700 cycles. The root cause of electrode polarization, initial capacity fading, and electrode swelling is discussed and has profound implications for the development of stable lithium‐ion batteries.