Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection

Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats

An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability

Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model

Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages

Oxygen is a critical parameter proposed to modulate the functions of chondrocytes ex-vivo as well as in damaged joints. This article investigates the effect of low (more physiological) oxygen percentage on the biosynthetic and catabolic activity of human articular chondrocytes (HAC) at different phases of in vitro culture

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to- DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation

MMBnet 2017 - Proceedings of the 9th GI/ITG Workshop „Leistungs-, Verlässlichkeits- und Zuverlässigkeitsbewertung von Kommunikationsnetzen und Verteilten Systemen“

Nowadays, mathematical methods of systems and network monitoring, modeling, simulation, and performance, dependability and reliability analysis constitute the foundation of quantitative evaluation methods with regard to software-defined next-generation networks and advanced cloud computing systems. Considering the application of the underlying methodologies in engineering practice, these sophisticated techniques provide the basis in many different areas. The GI/ITG Technical Committee “Measurement, Modelling and Evaluation of Computing Systems“ (MMB) and its members have investigated corresponding research topics and initiated a series of MMB conferences and workshops over the last decades. Its 9th GI/ITG Workshop MMBnet 2017 „Leistungs-, Verlässlichkeits- und Zuverlässigkeitsbewertung von Kommunikationsnetzen und Verteilten Systemen“ was held at Hamburg University of Technology (TUHH), Germany, on September 14, 2017. The proceedings of MMBnet 2017 summarize the contributions of one invited talk and four contributed papers of young researchers. They deal with current research issues in next-generation networks, IP-based real-time communication systems, and new application architectures and intend to stimulate the reader‘s future research in these vital areas of modern information society

Spiders in caves: the CAWEB project

World experts of different disciplines, from molecular biology to macroecology, recognize the value of cave ecosystems as ideal ecological and evolutionary laboratories. Among other subterranean taxa, spiders stand out as intriguing model organisms for their ecological role of top-predators, their unique adaptations to the hypogean medium and their sensitivity to anthropogenic disturbance. Here, we provide a general overview of the spider families recorded in hypogean habitats in Europe–20 families including nearly 500 species, most of them with restricted distributions. We also review the different adaptations of hypogean spiders to subterranean life and summarize the information gathered so far about their origin, population structure, ecology and conservation status. Taxonomic knowledge on subterranean spiders in Europe appears to be well, but not exhaustively documented. The origin of the European assemblages is mostly explained by past climate dynamics, although other factors are likely to be involved. Most of the macroecological issues related to spiders in European caves are based on qualitative assessments or have been quantified only at a sub-regional scale. In order to shed light on cave spiders’ biogeography and the macroecological patterns driving the diversity of European subterranean spiders we created the CAWEB network, a spontaneous collaboration between subterranean arachnologists from 30 different European countries. We here present the team and provide some preliminary results, which highlight Southern Europe as an important hot-spot for the European subterranean spider diversity

Continental data on cave-dwelling spider communities across Europe (Arachnida: Araneae)

Background Spiders (Arachnida: Araneae) are widespread in subterranean ecosystems worldwide and represent an important component of subterranean trophic webs. Yet, global-scale diversity patterns of subterranean spiders are still mostly unknown. In the frame of the CAWEB project, a European joint network of cave arachnologists, we collected data on cave dwelling spider communities across Europe in order to explore their continental diversity patterns. Two main datasets were compiled: one listing all subterranean spider species recorded in numerous subterranean localities across Europe and another with high resolution data about the subterranean habitat in which they were collected. From these two datasets, we further generated a third dataset with individual geo-referenced occurrence records for all these species. New information Data from 475 geo-referenced subterranean localities (caves, mines and other artificial subterranean sites, interstitial habitats) are herein made available. For each subterranean locality, information about the composition of the spider community is provided, along with local geomorphological and habitat features. Altogether, these communities account for > 300 unique taxonomic entities and 2,091 unique geo-referenced occurrence records, that are made available via the Global Biodiversity Information Facility (GBIF) (Mammola and Cardoso 2019). This dataset is unique in that it covers both a large geographic extent (from 35 south to 67 degrees north) and contains high-resolution local data on geomorphological and habitat features. Given that this kind of high-resolution data are rarely associated with broad-scale datasets used in macroecology, this dataset has high potential for helping researchers in tackling a range of biogeographical and macroecological questions, not necessarily uniquely related to arachnology or subterranean biology