Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis

Contains fulltext : 238107.pdf (Publisher’s version ) (Closed access)Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated phagocytosis (LAP) and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. In particular, we demonstrate that activation of LAP by the human fungal pathogen Aspergillus fumigatus depends on ERK1/2-mediated phosphorylation of p47phox subunit of NADPH oxidase. Physiologically, autocrine IL-6/JAK2/Ninein axis orchestrates microtubule organization and dynamics regulating ERK recruitment to the phagosome and LC3(+) phagosome (LAPosome) formation. In sepsis, loss of IL-6 signaling specifically abrogates microtubule-mediated trafficking of ERK, leading to defective activation of LAP and impaired killing of bacterial and fungal pathogens by monocytes/macrophages, which can be selectively restored by IL-6 supplementation. Our work uncovers a molecular pathway linking IL-6 signaling with LAP and provides insight into the mechanisms underlying immunoparalysis in sepsis

Ατυχηματική εγρήγορση κατά τη γενική αναισθησία

Εισαγωγή: Ο τομέας της αναισθησιολογίας απασχολεί όλο και περισσότερο τους επαγγελματίες υγείας αφού οι εξελίξεις της επιστήμης και της τεχνολογίας έχουν επιτρέψει τη βελτίωση της παροχής φροντίδας, πιο ασφαλείς διαδικασίες για το προσωπικό και τους ασθενείς αλλά και μείωση των ανεπιθύμητων ενεργειών της αναισθησίας. Μια ανεπιθύμητη ενέργεια είναι και η ατυχηματική εγρήγορση η οποία μπορεί να μην συμβαίνει συχνά, 0,1% - 0,2% στον γενικό πληθυσμό, αλλά είναι αρκετά δυσμενής καθώς ο ασθενής αποκτά συνείδηση κατά τη διάρκεια του χειρουργείου και έχει τη δυνατότητα να ανακαλέσει αυτές τις στιγμές αφού ανανήψει. Σκοπός: Ο σκοπός της εργασίας είναι η διερεύνηση και ανάλυση της ατυχηματικής εγρήγορσης κατά τη γενική αναισθησία. Θα αναφερθούν τα αίτια εμφάνισής της και οι παράγοντες κινδύνου, οι τρόποι παρακολούθησης του βάθους της αναισθησίας καθώς και οι συνέπειες που μπορεί να επιφέρει στη ζωή του ασθενή. Μεθοδολογία: Για τη συλλογή των μελετών της παρούσας εργασίας χρησιμοποιήθηκαν οι παρακάτω λέξεις κλειδιά: accidental intraoperative awareness, awareness with recall, intraoperative awareness, awareness anesthesia στις βάσεις δεδομένων Pubmed, Cinahl, Google Scholar. Χρησιμοποιήθηκαν μόνο άρθρα στην Αγγλική και Ελληνική γλώσσα τα οποία είχαν δημοσιευθεί τα τελευταία 30 έτη. Συμπεράσματα: Η εμφάνιση της ατυχηματικής εγρήγορσης κατά τη γενική αναισθησία σχετίζεται με τη φυσική κατάσταση και τα ιδιαίτερα χαρακτηριστικά του κάθε ασθενή αλλά και από το είδος της επέμβασης που πρόκειται να υποβληθεί. Επίσης, ρόλο διαδραματίζει και το είδος της αναισθησίας που χρησιμοποιείται αλλά και η κατάσταση του εξοπλισμού που χορηγεί την αναισθησία όπως και στον ανθρώπινο δυναμικό που τον χειρίζεται. Η ατυχηματική εγρήγορση φαίνεται να μπορεί να δημιουργήσει ακόμα και αγχωτικό μετατραυματικό σύνδρομο σε κάποιους ασθενείς. Θετικό είναι το γεγονός ότι η τεχνολογία έχει συνδράμει στη μείωση αυτού του φαινομένου έχοντας δώσει τη δυνατότητα παρακολούθησης του βάθους της αναισθησίας με κυρίαρχο εργαλείο το monitor BIS.Introduction: The field of anesthesiology has increasing concerns amongst healthcare professionals since the development of science and technology allows improvement in the field of provided care, safer procedures for both patients and caregivers but also a decrease to the unpleasant and unexpected side effects of anaesthesia. One of the side effects is the intraoperative accidental awareness, which even though might not happen often , 0,1% - 0,2% of the general population, is however an extremely unpleasant experience since the patient gains consciousness during their surgery and recalls memories later on. Purpose: The purpose of this paper is to detect and analyse the phenomenon of accidental awareness during general anesthesia. Its causes, risk factors, ways of monitoring the depth of the anesthesia, as well as its consequences on the patient's life will all be mentioned. Methodology: For the collection of the studies the following keywords were used: accidental intraoperative awareness, awareness with recall, intraoperative awareness, awareness anesthesia in Pubmed, Cinahl, Google Scholar databases. The articles that were used, were in English or Greek and had been published within the past 30 years. Conclusions: The occurrence of accidental awareness during general anesthesia is related to the physical condition and the particular characteristics of each individual.In addition, the type of surgery being performed, condition of the equipment with which anesthesia is administered, the type of anesthesia as well as the human personnel handling it all play a role. Post-traumatic stress disorder is a possible side effect in some patients. On a positive note and with the help of technology, this phenomenon has been reduced by enabling a dominant tool ,the BIS monitor, to monitor the depth of anesthesia

The effect of mild pyrolysis on the kinetics of co-combustion of lignite N.Pediou Ptolemaidas with agricultural and industrial waste

Περίληψη: Το αντικείμενο της παρούσας εργασίας ήταν η μελέτη της θερμικής και κινητικής συμπεριφοράς βιομαζικών υλικών (άγριας αγκινάρας, στελέχη βαμβακιού και στερεά αποβλητογενή καύσιμα) κατά τη συν-καύση τους με λιγνίτη Πτολεμαΐδας, Νοτίου Πεδίου. Πραγματοποιήθηκε θερμοβαρυτoμετρική ανάλυση (ΤGΑ/DTG) των δειγμάτων για τον προσδιορισμό των χαρακτηριστικών παραμέτρων της καύσης. Επίσης, διεξήχθησαν πειράματα ήπιας πυρόλυσης στα βιομαζικά δείγματα σε αντιδραστήρα σταθερής κλίνης, με σκοπό την αύξηση της ενεργειακής τους πυκνότητας. Τέλος, αναπτύχθηκε κινητικό μοντέλο, που αποσκοπούσε στην κινητική της καύσης και τον προσδιορισμό των κινητικών παραμέτρων. Η θερμοχημική αντιδραστικότητα των βιομαζικών υλικών ήταν υψηλότερη από αυτή του λιγνίτη. Η καύση των πυρολυμένων δειγμάτων πραγματοποιήθηκε σε υψηλότερες θερμοκρασίες με μικρότερο ρυθμό, ομοιάζοντας περισσότερο με τη θερμική συμπεριφορά του λιγνίτη. Τα μίγματα λιγνίτη/βιομάζας παρουσίασαν φαινόμενα συνέργειας. Η προσαρμογή του κινητικού μοντέλου ήταν καλή, καθώς η απόκλιση κυμάνθηκε από 3-7%. Η ενέργεια ενεργοποίησης του λιγνίτη και των μιγμάτων με τα βιομαζικά υλικά ήταν 80-223kJ/mol

Structural Correlates of CA2 and CA3 Pyramidal Cell Activity in Freely-Moving Mice

Plasticity within hippocampal circuits is essential for memory functions. The hippocampal CA2/CA3 region is thought to be able to rapidly store incoming information by plastic modifications of synaptic weights within its recurrent network. High-frequency spike-bursts are believed to be essential for this process, by serving as triggers for synaptic plasticity. Given the diversity of CA2/CA3 pyramidal neurons, it is currently unknown whether and how burst activity, assessed in vivo during natural behavior, relates to principal cell heterogeneity. To explore this issue, we juxtacellularly recorded the activity of single CA2/CA3 neurons from freely-moving male mice, exploring a familiar environment. In line with previous work, we found that spatial and temporal activity patterns of pyramidal neurons correlated with their topographical position. Morphometric analysis revealed that neurons with a higher proportion of distal dendritic length displayed a higher tendency to fire spike-bursts. We propose that the dendritic architecture of pyramidal neurons might determine burst-firing by setting the relative amount of distal excitatory inputs from the entorhinal cortex

Manipulating Hippocampal Place Cell Activity by Single-Cell Stimulation in Freely Moving Mice

Summary: Learning critically depends on the ability to rapidly form and store non-overlapping representations of the external world. In line with their postulated role in episodic memory, hippocampal place cells can undergo a rapid reorganization of their firing fields upon contextual manipulations. To explore the mechanisms underlying such global remapping, we juxtacellularly stimulated 42 hippocampal neurons in freely moving mice during spatial exploration. We found that evoking spike trains in silent neurons was sufficient for creating place fields, while in place cells, juxtacellular stimulation induced a rapid remapping of their place fields to the stimulus location. The occurrence of complex spikes was most predictive of place field plasticity. Our data thus indicate that plasticity-inducing stimuli are able to rapidly bias place cell activity, simultaneously suppressing existing place fields. We propose that such competitive place field dynamics could support the orthogonalization of the hippocampal map during global remapping. : Place cells can serve as a readout of hippocampal memory. Diamantaki et al. show that the activity of single place cells can be rapidly modified by single-cell stimulation in freely moving mice. This finding provides insights into the cellular mechanisms that support the rapid reorganization of hippocampal place maps

Replication Data for: A simulated roadmap of hydrogen technology contribution to climate change mitigation based on Representative Concentration Pathways considerations.

Hydrogen as fuel has been a promising technology towards climate change mitigation efforts. Having this said, this work analyses the contribution of the technology to future global environmental goals. It is assumed that hydrogen is being produced in higher efficiency across time, as it is indicated to hydrogen source code and this is simulated on Global Change Assessment Model (GCAM) v4.3. The environmental restrictions applied are the expected emissions Representative Concentration Pathways (RCP) 2.6, 4.5, and 6.0

Exploring the significance of morphological diversity for cerebellar granule cell excitability

The relatively simple and compact morphology of cerebellar granule cells (CGCs) has led to the view that heterogeneity in CGC shape has negligible impact upon the integration of mossy fibre (MF) information. Following electrophysiological recording, 3D models were constructed from high-resolution imaging data to identify morphological features that could influence the coding of MF input patterns by adult CGCs. Quantification of MF and CGC morphology provided evidence that CGCs could be connected to the multiple rosettes that arise from a single MF input. Predictions from our computational models propose that MF inputs could be more densely encoded within the CGC layer than previous models suggest. Moreover, those MF signals arriving onto the dendrite closest to the axon will generate greater CGC excitation. However, the impact of this morphological variability on MF input selectivity will be attenuated by high levels of CGC inhibition providing further flexibility to the MF. CGC pathway. These features could be particularly important when considering the integration of multimodal MF sensory input by individual CGCs

Heterogeneous orientation tuning in the primary visual cortex of mice diverges from Gabor-like receptive fields in primates

http://dx.doi.org/10.13039/100010688 Horizon 2020 European Innovation Council Fast Track to Innovationhttp://dx.doi.org/10.13039/100011039 IARPAhttp://dx.doi.org/10.13039/100015388 Kansas NSF EPSCoRhttp://dx.doi.org/10.13039/501100008897 Nihon Superiorhttp://dx.doi.org/10.13039/100022709 Cluster of Excellence on Plant Scienceshttp://dx.doi.org/10.13039/100006133 Advanced Research Projects Agency - Energyhttp://dx.doi.org/10.13039/100000185 DARPAhttp://dx.doi.org/10.13039/100018707 HORIZON EUROPE Reforming and enhancing the European Research and Innovation systemhttp://dx.doi.org/10.13039/100027697 Neighbor Uphttp://dx.doi.org/10.13039/100000002 NIHhttp://dx.doi.org/10.13039/100007569 Carl-Zeiss-Stiftunghttp://dx.doi.org/10.13039/100013177 Interior Business Centerhttp://dx.doi.org/10.13039/501100016986 International Max Planck Research School for Precision Tests of Fundamental Symmetrieshttp://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaf

Combustion performance and kinetic modeling of lignite blended with torrefied biomass of different origin

Summarization: Biomass materials of different origin were upgraded by torrefaction and blended with lignite. Combustion characteristics, reactivity, and synergistic effects were determined through thermal analysis tests. An independent parallel reactions model was developed to describe combustion kinetics. According to the results, torrefaction delayed ignition and reduced the reactivity of biomass fuels. Blending of lignite with either raw or torrefied materials exhibited some synergy and improved the reactivity of lignite up to two times/fold. The model applied fitted the experimental results accurately. The kinetic parameters of lignite/torrefied biomass blends were closer to the values corresponding to lignite (ΔΕl = 74–235 kJ/mol, ΔΕl/t biomass = 80–223 kJ/mol), pointing to a higher similarity in mechanism of combustion and thermal behavior.Presented on: International Journal of Green Energ

H2020 ACCEPT project: D2.4 -ACCEPT system architecture description v2

This report presents the work carried out in Task 2.3 of ACCEPT regarding the system architecture design process and results up to the date of submission of the second version of the deliverable. In particular, the deliverable includes the high-level architecture model of the complete system, with the initial point being the design as presented in the Description of Work, and further refined and updated based on the work carried out in this period. This high-level architecture has also been mapped to the various SGAM layers to assist the future integration and development activities. The main bulk of the document concentrates on detailing the specifications and characteristics of the various system's software components. A dedicated template was created and circulated to all relevant partners in order to provide the components' functional and non-functional specifications, highlight interdependencies with other components, and declare the input/output data requirements (Annex I – Component’s Specifications and Requirements Template). Additionally, detailed component diagrams were created, and finally, the connection with Deliverable 2.1 (D2.1) was performed via a mapping of components to Use Cases that required relevant functionalities. Sequence diagrams were already created for D2.1 and are not presented here. A new section was created for the second version of the deliverable; it includes an update of the Use Cases, as described in D2.1, following necessary refinements and modifications that occurred in the course of the project. Similarly, the SGAM mapping, the component description and diagrams were updated to reflect the advances of the project. This is the second and final version of ACCEPT's system architecture. It will drive the development of the second and final iteration of the system and its constituent components. Following that, further refinements, if necessary, will be integrated in the new versions of the different components of the projec