Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

In the pathogenesis of multiple sclerosis (MS), oligodendrocytes and its myelin sheaths are thought to be the primary target of destruction. The mechanism leading to oligodendrocyte injury and demyelination is still elusive. Oligodendrocytes are maintaining up to 50 internodes of myelin, which is an extraordinary metabolic demand. This makes them one of the most vulnerable cell types in the central nervous system (CNS), and even small insults can lead to oligodendrocyte impairment, demyelination, and axonal dysfunction. For this reason, oligodendrocytes are viewed as more or less the "lame ducks” of the CNS who can easily become victims. However, recent data demonstrate that this perception possibly needs to be revised. The latest data suggest that oligodendrocytes may also act as "fierce creatures,” influencing the surrounding cells in many ways to preserve its own, as well as their function, allowing sustained functionality of the CNS upon an attack. In this review, the concept of "reactive or activated oligodendrocyte” is introduced, describing alterations in oligodendrocytes which are either protective mechanisms allowing survival in otherwise lethal environment or influence and possibly modulate the ongoing inflammation. Although "harnessed”, oligodendrocytes might actively modulate and shape their environment and be part of the immune privilege of the brai

Single crystal field-effect transistors based on an organic selenium-containing semiconductor

We report on the fabrication and characterization of single crystal field-effect transistors (FETs) based on diphenylbenzo diselenophene (DPh-BDSe). These organic field-effect transistors (OFETs) function as p-channel accumulation-mode devices. At room temperature, for the best devices, the threshold voltage is less than -7V and charge carrier mobility is nearly gate bias independent, ranging from 1cm2/Vs to 1.5 cm2/Vs depending on the source-drain bias. Mobility is increased slightly by cooling below room temperature and decreases below 280 K

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

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

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

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

Strong differences in the clonal variation of two Daphnia species from mountain lakes affected by overwintering strategy

<p>Abstract</p> <p>Background</p> <p>The population structure of cyclical parthenogens such as water fleas is strongly influenced by the frequency of alternations between sexual and asexual (parthenogenetic) reproduction, which may differ among populations and species. We studied genetic variation within six populations of two closely related species of water fleas of the genus <it>Daphnia </it>(Crustacea, Cladocera). <it>D. galeata </it>and <it>D. longispina </it>both occur in lakes in the Tatra Mountains (Central Europe), but their populations show distinct life history strategies in that region. In three studied lakes inhabited by <it>D. galeata</it>, daphnids overwinter under the ice as adult females. In contrast, in lakes inhabited by <it>D. longispina</it>, populations apparently disappear from the water column and overwinter as dormant eggs in lake sediments. We investigated to what extent these different strategies lead to differences in the clonal composition of late summer populations.</p> <p>Results</p> <p>Analysis of genetic variation at nine microsatellite loci revealed that clonal richness (expressed as the proportion of different multilocus genotypes, MLGs, in the whole analysed sample) consistently differed between the two studied species. In the three <it>D. longispina </it>populations, very high clonal richness was found (MLG/N ranging from 0.97 to 1.00), whereas in <it>D. galeata </it>it was much lower (0.05 to 0.50). The dominant MLGs in all <it>D. galeata </it>populations were heterozygous at five or more loci, suggesting that such individuals all represented the same clonal lineages rather than insufficiently resolved groups of different clones.</p> <p>Conclusions</p> <p>The low clonal diversities and significant deviations from Hardy-Weinberg equilibrium in <it>D. galeata </it>populations were likely a consequence of strong clonal erosion over extended periods of time (several years or even decades) and the limited influence of sexual reproduction. Our data reveal that populations of closely related <it>Daphnia </it>species living in relatively similar habitats (permanent, oligotrophic mountain lakes) within the same region may show strikingly different genetic structures, which most likely depend on their reproductive strategy during unfavourable periods. We assume that similar impacts of life history on population structures are also relevant for other cyclical parthenogen groups. In extreme cases, prolonged clonal erosion may result in the dominance of a single clone within a population, which might limit its microevolutionary potential if selection pressures suddenly change.</p