Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Respiratory plasticity in response to changes in oxygen supply and demand

Aerobic organisms maintain O2 homeostasis by responding to changes in O2 supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O2 supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O2 capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O2 supply and deman

Porous N- and S-doped carbon-carbon composite electrodes by soft-templating for redox flow batteries

Highly porous carbon–carbon composite electrodes for the implementation in redox flow battery systems have been synthesized by a novel soft-templating approach. A PAN-based carbon felt was embedded into a solution containing a phenolic resin, a nitrogen source (pyrrole-2-carboxaldehyde) and a sulfur source (2-thiophenecarboxaldehyde), as well as a triblock copolymer (Pluronic® F-127) acting as the structure-directing agent. By this strategy, highly porous carbon phase co-doped with nitrogen and sulfur was obtained inside the macroporous carbon felt. For the investigation of electrode structure and porosity X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and nitrogen sorption (BET) were used. The electrochemical performance of the carbon felts was evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The N- and S-doped carbon electrodes show promising activity for the positive side reaction and could be seen as a significant advance in the design of carbon felt electrodes for use in redox flow batteries

Multimodal characterization of carbon electrodes\u27 thermal activation for vanadium redox flow batteries

Thermal activation has proven to be a valuable procedure to improve the performance of carbon electrodes in vanadium redox flow batteries (VRFBs). This work investigates how different activation temperatures impact the rayon-based carbon felt\u27s structure, surface composition, wettability, and electrochemical activity. A unique combination of non-standard techniques, including atomic force microscopy (AFM), dynamic vapor sorption (DVS), and electrochemical impedance spectroscopy (EIS) combined with the distribution of relaxation times (DRT) analysis, was used for the first time in the context of VRFB electrodes. The wettability of the carbon felts improved, and the process impedances decreased with higher activation temperatures. However, severe carbon decomposition occurs at high activation temperatures. The optimum electrochemical performance of the carbon felts in the vanadium(IV)/vanadium(V) redox reaction was observed after activation at 400 °C. Thus, we conclude that the optimum activation temperature for this type of carbon felt concerning the investigated properties is around 400 °C. Furthermore, we want to highlight the successful approach of using AFM, DVS, and EIS combined with DRT analysis for an integral investigation of key properties such as structure, wettability, and performance of VRFB electrodes

Impact of catalyst layer morphology on the operation of high temperature PEM fuel cells

Electrochemical impedance spectroscopy (EIS) is a well-established method to analyze a polymer electrolyte membrane fuel cell (PEMFC). However, without further data processing, the impedance spectrum yields only qualitative insight into the mechanism and individual contribution of transport, kinetics, and ohmic losses to the overall fuel cell limitations. The distribution of relaxation times (DRT) method allows quantifying each of these polarization losses and evaluates their contribution to a given electrocatalyst\u27s depreciated performances. We coupled this method with a detailed morphology study to investigate the impact of the 3D-structure on the processes occurring inside a high-temperature polymer electrolyte membrane fuel cell (HT-PEMFC). We tested a platinum catalyst (Pt/C), a platinum-cobalt alloy catalyst (Pt$_{3}$Co/C), and a platinum group metal-free iron-nitrogen-carbon (Fe–N–C) catalyst. We found that the hampered mass transport in the latter is mainly responsible for its low performance in the MEA (along with its decreased intrinsic performances for the ORR reaction). The better performance of the alloy catalyst can be explained by both improved mass transport and a lower ORR resistance. Furthermore, single-cell tests show that the catalyst layer morphology influences the distribution of phosphoric acid during conditioning

Deciphering the regulatory landscapte of fetal and adult γδ T-cell development at single-cell resolution

γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high‐resolution map of γδ T‐cell differentiation from the fetal and adult thymus using single‐cell RNA sequencing. We reveal novel sub‐types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T‐cell differentiation. By performing a combined single‐cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL ‐17‐producing γδ T‐cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T‐cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages

Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status

BACKGROUND: Macrophages play a dual role in multiple sclerosis (MS) pathology. They can exert neuroprotective and growth promoting effects but also contribute to tissue damage by production of inflammatory mediators. The effector function of macrophages is determined by the way they are activated. Stimulation of monocyte-derived macrophages in vitro with interferon-γ and lipopolysaccharide results in classically activated (CA/M1) macrophages, and activation with interleukin 4 induces alternatively activated (AA/M2) macrophages. METHODS: For this study, the expression of a panel of typical M1 and M2 markers on human monocyte derived M1 and M2 macrophages was analyzed using flow cytometry. This revealed that CD40 and mannose receptor (MR) were the most distinctive markers for human M1 and M2 macrophages, respectively. Using a panel of M1 and M2 markers we next examined the activation status of macrophages/microglia in MS lesions, normal appearing white matter and healthy control samples. RESULTS: Our data show that M1 markers, including CD40, CD86, CD64 and CD32 were abundantly expressed by microglia in normal appearing white matter and by activated microglia and macrophages throughout active demyelinating MS lesions. M2 markers, such as MR and CD163 were expressed by myelin-laden macrophages in active lesions and perivascular macrophages. Double staining with anti-CD40 and anti-MR revealed that approximately 70% of the CD40-positive macrophages in MS lesions also expressed MR, indicating that the majority of infiltrating macrophages and activated microglial cells display an intermediate activation status. CONCLUSIONS: Our findings show that, although macrophages in active MS lesions predominantly display M1 characteristics, a major subset of macrophages have an intermediate activation status

Synchrotron X-ray Radiography and Tomography of Vanadium Redox Flow Batteries—Cell Design, Electrolyte Flow Geometry, and Gas Bubble Formation

The wetting behavior and affinity to side reactions of carbon‐based electrodes in vanadium redox flow batteries (VRFBs) are highly dependent on the physical and chemical surface structures of the material, as well as on the cell design itself. To investigate these properties, a new cell design was proposed to facilitate synchrotron X‐ray imaging. Three different flow geometries were studied to understand the impact on the flow dynamics, and the formation of hydrogen bubbles. By electrolyte injection experiments, it was shown that the maximum saturation of carbon felt was achieved by a flat flow field after the first injection and by a serpentine flow field after continuous flow. Furthermore, the average saturation of the carbon felt was correlated to the cyclic voltammetry current response, and the hydrogen gas evolution was visualized in 3D by X‐ray tomography. The capabilities of this cell design and experiments were outlined, which are essential for the evaluation and optimization of cell components of VRFBs

High Electron Mobility in Vacuum and Ambient for PDIF-CN2 Single-Crystal Transistors

We have investigated the electron mobility on field-effect transistors based on PDIF-CN$_{2}$ single crystals. The family of the small molecules PDI8-CN$_{2}$ has been chosen for the promising results obtained for vapour-deposited thin film FETs. We used as gate dielectric a layer of PMMA (spinned on top of the SiO$_{2}$), to reduce the possibility of electron trapping by hydroxyl groups present at surface of the oxide. For these devices we obtained a room temperature mobility of 6 cm$^{2}$/Vs in vacuum and 3 cm$^{2}$/Vs in air. Our measurements demonstrate the possibility to obtain n-type OFETs with performances comparable to those of p-type devices.Comment: published online in JAC