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Viktoria Fischer Martin Both Andreas Draguhn Alexei V. Egorov 《Journal of neurochemistry》2014,129(5):792-805
The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave–ripple complexes (SPW‐R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7‐containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks.
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Laura C. Burzynski Melanie Humphry Martin R. Bennett Murray C. H. Clarke 《The Journal of biological chemistry》2015,290(41):25188-25196
Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection. 相似文献
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Reduced Recombination in High Efficiency Molecular Nematic Liquid Crystalline: Fullerene Solar Cells 下载免费PDF全文
Ardalan Armin Jegadesan Subbiah Martin Stolterfoht Safa Shoaee Zeyun Xiao Shirong Lu David J. Jones Paul Meredith 《Liver Transplantation》2016,6(22)
Bimolecular recombination in bulk heterojunction organic solar cells is the process by which nongeminate photogenerated free carriers encounter each other, and combine to form a charge transfer (CT) state which subsequently relaxes to the ground state. It is governed by the diffusion of the slower and faster carriers toward the electron donor–acceptor interface. In an increasing number of systems, the recombination rate constant is measured to be lower than that predicted by Langevin's model for relative Brownian motion and the capture of opposite charges. This study investigates the dynamics of charge generation, transport, and recombination in a nematic liquid crystalline donor:fullerene acceptor system that gives solar cells with initial power conversion efficiencies of >9.5%. Unusually, and advantageously from a manufacturing perspective, these efficiencies are maintained in junctions thicker than 300 nm. Despite finding imbalanced and moderate carrier mobilities in this blend, strongly suppressed bimolecular recombination is observed, which is ≈150 times less than predicted by Langevin theory, or indeed, more recent and advanced models that take into account the domain size and the spatial separation of electrons and holes. The suppressed bimolecular recombination arises from the fact that ground‐state decay of the CT state is significantly slower than dissociation. 相似文献
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Alfred Burian Martin J. Kainz Michael Schagerl Andrew Yasindi 《Freshwater Biology》2014,59(6):1257-1265
- The analysis of functional groups with a resolution to the individual species level is a basic requirement to better understand complex interactions in aquatic food webs. Species‐specific stable isotope analyses are currently applied to analyse the trophic role of large zooplankton or fish species, but technical constraints complicate their application to smaller‐sized plankton.
- We investigated rotifer food assimilation during a short‐term microzooplankton bloom in the East African soda lake Nakuru by developing a method for species‐specific sampling of rotifers.
- The two dominant rotifers, Brachionus plicatilis and Brachionus dimidiatus, were separated to single‐species samples (purity >95%) and significantly differed in their isotopic values (4.1‰ in δ13C and 1.5‰ in δ15N). Bayesian mixing models indicated that isotopic differences were caused by different assimilation of filamentous cyanobacteria and particles <2 μm and underlined the importance of species‐specific sampling of smaller plankton compartments.
- A main difference was that the filamentous cyanobacterium Arthrospira fusiformis, which frequently forms blooms in African soda lakes, was an important food source for the larger‐sized B. plicatilis (48%), whereas it was hardly ingested by B. dimidiatus. Overall, A. fusiformis was, relative to its biomass, assimilated to small extents, demonstrating a high grazing resistance of this species.
- In combination with high population densities, these results demonstrate a strong potential of rotifer blooms to shape phytoplankton communities and are the first in situ demonstration of a quantitatively important direct trophic link between rotifers and filamentous cyanobacteria.
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In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears. 相似文献
10.
Fianne L. P. Sips Elin Nyman Martin Adiels Peter A. J. Hilbers Peter Str?lfors Natal A. W. van Riel Gunnar Cedersund 《PloS one》2015,10(9)
In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30–45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease. 相似文献