Structural studies on Ca3Al4MgO10 (C3A2M)—A ternary phase in the system CaO–Al2O3–MgO

In a sequence of temperature-dependent solid-state reactions in the system CaO–Al₂O₃–MgO the formation of the ternary phase Ca₃Al₄MgO₁₀ or C₃A₂M has been studied. Whereas the compound could not be prepared at 1200°C, a yield of 85 wt.-% of Ca₃Al₄MgO₁₀ was obtained at 1320°C (incongruent melting point: 1330°C). Powder diffraction data compare well with results of previous investigations from the 1960s. Single crystals of Ca₃Al₄MgO₁₀ could be retrieved from the sinter-pellets. Basic crystallographic data are as follows: orthorhombic symmetry, space group Pbcm, a = 5.14073(8), b = 16.7576(2), c = 10.70977(16) Å, V = 922.61(2) ų, Z = 4. Using synchrotron diffraction data it was possible to solve the crystal structure. Least-squares refinements resulted in a residual of R(|F|) = 0.021 for 1000 independent observed reflections with I > 2σ(I) and 97 parameters. The structure contains [TO₄]-tetrahedra (T=Al,Mg) forming a three-dimensional (3-D) framework whose topological characteristics have been determined. Al-Mg distributions on the different T-sites have been studied. The calcium cations are located in voids of the network. More than 50 years after its first observation our investigation clarifies the crystal structure of a compound belonging to a system that is of relevance for several fields of materials science.     

Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.     

Mild Muscle Mitochondrial Fusion Distress Extends Drosophila Lifespan through an Early and Systemic Metabolome Reorganization

In a global aging population, it is important to understand the factors affecting systemic aging and lifespan. Mitohormesis, an adaptive response caused by different insults affecting the mitochondrial network, triggers a response from the nuclear genome inducing several pathways that promote longevity and metabolic health. Understanding the role of mitochondrial function during the aging process could help biomarker identification and the development of novel strategies for healthy aging. Herein, we interfered the muscle expression of the Drosophila genes Marf and Opa1, two genes that encode for proteins promoting mitochondrial fusion, orthologues of human MFN2 and OPA1. Silencing of Marf and Opa1 in muscle increases lifespan, improves locomotor capacities in the long term, and maintains muscular integrity. A metabolomic analysis revealed that muscle down-regulation of Marf and Opa1 promotes a non-autonomous systemic metabolome reorganization, mainly affecting metabolites involved in the energetic homeostasis: carbohydrates, lipids and aminoacids. Interestingly, the differences are consistently more evident in younger flies, implying that there may exist an anticipative adaptation mediating the protective changes at the older age. We demonstrate that mild mitochondrial muscle disturbance plays an important role in Drosophila fitness and reveals metabolic connections between tissues. This study opens new avenues to explore the link of mitochondrial dynamics and inter-organ communication, as well as their relationship with muscle-related pathologies, or in which muscle aging is a risk factor for their appearance. Our results suggest that early intervention in muscle may prevent sarcopenia and promote healthy aging.     

Generation of a Triadin KnockOut Syndrome Zebrafish Model

Different forms of sudden cardiac death have been described, including a recently identified form of genetic arrhythmogenic disorder, named “Triadin KnockOut Syndrome” (TKOS). TKOS is associated with recessive mutations in the TRDN gene, encoding for TRIADIN, but the pathogenic mechanism underlying the malignant phenotype has yet to be completely defined. Moreover, patients with TKOS are often refractory to conventional treatment, substantiating the need to identify new therapeutic strategies in order to prevent or treat cardiac events. The zebrafish (Danio rerio) heart is highly comparable to the human heart in terms of functions, signal pathways and ion channels, representing a good model to study cardiac disorders. In this work, we generated the first zebrafish model for trdn loss-of-function, by means of trdn morpholino injections, and characterized its phenotype. Although we did not observe any gross cardiac morphological defect between trdn loss-of-function embryos and controls, we found altered cardiac rhythm that was recovered by the administration of arrhythmic drugs. Our model will provide a suitable platform to study the effect of TRDN mutations and to perform drug screening to identify new pharmacological strategies for patients carrying TRDN mutations.     

Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.     

Online monitoring of the curing of adhesives with a miniaturised interdigital sensor using impedance spectroscopy

Monitoring adhesives during manufacturing and their lifetime has become increasingly important due to the variety of materials and applications. Impedance spectroscopy is a suitable method for online monitoring of the curing process. We present a miniaturised interdigital structure to monitor the curing process of the adhesives using impedance spectroscopy. Compared to other sensors, our sensor is ultrathin, so that it disappears in the adhesive joint. Therefore, it can remain in the joint and be used for lifetime monitoring. In addition it is suitable for thin adhesive layers due to its fine grid. We demonstrate that the impedance of the sensor embedded in the adhesive gives insight into the curing mechanisms. Therefore monitoring of a dispersion and an epoxy is shown. In addition, the curing cycles can be reliably controlled using this monitoring method. The permittivity of the adhesives is extracted from the impedance measurements, applying analytical models of the electrical field of the interdigital structure.     

Temperature‐dependent coefficient of thermal expansion (CTE) of injection molded,short‐glass‐fiber‐reinforced polymers

A deep understanding of the anisotropic, composite‐, geometry‐, and temperature‐dependent coefficient of thermal expansion (CTE) of short‐fiber‐reinforced polymers is often needed in material development and at early stages of the design process of injection molded parts. Usually, the data available does not reflect the complex behavior and the knowledge about the influences and interactions are missing. This paper deals with a method for calculating the composite‐, geometry‐, and temperature‐dependent anisotropic CTE of parts made from short‐fiber reinforced polymers without respectively low preload to create an understanding of its origins and influential factors. Here, a good accordance between the measurements and calculations was achieved. POLYM. ENG. SCI., 55:2661–2668, 2015. © 2015 Society of Plastics Engineers     

Fiber formation and properties of polyester/lignin blends

Thermotropic liquid crystalline polyesters with varied chemical structure are synthesized by melt transesterification polycondensation. They are employed as matrix for blends with lignin materials to obtain melt-spinnable precursors for carbon fibers. The lignin samples are carefully purified by fractionation, enzymatic removal of reducing sugars, and subsequent modification of the terminal OH groups. Effective melt blending is achieved with liquid-crystalline aromatic–aliphatic polyesters having melting ranges that match the softening temperature of the lignin fractions, which is necessary to prevent thermal decomposition of the lignin. Polyester/lignin blends are partially compatibilized, phase-separated materials. The polyester/lignin materials are melt-spun successfully. The fiber properties depend on the lignin purification process. X-ray scattering reveals that orientation in lignin-containing fibers is maintained. First experiments show that the fibers can be converted successfully to carbon fibers by thermal annealing procedures. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48257.     

Suspension and Mixing Characterization of Intermittent Agitation Modes in DASGIP Bioreactors

Intermittent agitation strategies have been increasingly used for a range of process development applications, i.e., to modulate physical cues, to improve stem cell differentiation yields, and to control hydrodynamic shear stresses in microcarrier suspension; however, there is a distinct lack of characterization. Both continuous and intermittent agitation modes in relation to suspension and mixing dynamics within a DASGIP bioreactor were characterized. Suspension dynamics were found to be affected by microcarrier porosity and the degree of settling was found to be more pronounced at the top of the bioreactor. Mixing time characterization showed a marked improvement in mixing efficiency for intermittent agitation, with an overall dependence on the timing of tracer insertion.