Dendritic Inhibition Effects in Memory Retrieval of a Neuromorphic Microcircuit Model of the Rat Hippocampus

Background: Studies have shown that input comparison in the hippocampus between the Schaffer collateral (SC) input in apical dendrites and the perforant path (PP) input in the apical tufts dramatically changes the activity of pyramidal cells (PCs). Equally, dendritic inhibition was shown to control PC activity by minimizing the depolarizing signals in their dendritic trees, controlling the synaptic integration time window, and ensuring temporal firing precision. Objectives: We computationally investigated the diverse roles of inhibitory synapses on the PC dendritic arbors of a CA1 microcircuit model in mnemonic retrieval during the co-occurrence of SC and PP inputs. Results: Our study showed inhibition in the apical PC dendrites mediated thresholding of firing during memory retrieval by restricting the depolarizing signals in the dendrites of non-engram cells, thus preventing them from firing, and ensuring perfect memory retrieval (only engram cells fire). On the other hand, inhibition in the apical dendritic tuft removed interference from spurious EC during recall. When EC drove only the engram cells of the SC input cue, recall was perfect under all conditions. Removal of apical tuft inhibition had no effect on recall quality. When EC drove 40% of engram cells and 60% of non-engram cells of the SC input cue, recall was disrupted, and this disruption was worse when the apical tuft inhibition was removed. When EC drove only the non-engram cells of the cue, then recall was perfect again but only when the population of engram cells was small. Removal of the apical tuft inhibition disrupted recall performance when the population of engram cells was large. Conclusions: Our study deciphers the divers

Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells

AbstractImmature dendritic cells (iDCs) have been shown to be able to induce peripheral T-cell tolerance through distinct pathways. Here, we investigated the tolerogenic property of recipient iDCs whose maturation was arrested by a dominant negative mutant of inhibitor of nuclear factor kappa-B kinase 2 (dnIKK2) gene. We found that dnIKK2-iDCs presented a typical semi-mature morphology and expressed lower levels of CD80 and CD86, slightly higher MHC-II than untransfected iDCs. The expression of these molecules had no significant change even dnIKK2-iDCs were pulsed by donor antigen. In primary mixed leukocyte reaction (MLR), dnIKK2-iDCs exhibited impaired ability to stimulate allogeneic T-cells, but induced CD4+CD25− T-cell formation. In co-culture MLR, these CD4+CD25− T-cells suppressed T-cell alloreaction in an antigen-specific manner. Besides, CD4+CD25− T-cells inhibited IL-2 and IFN-γ release, whereas promoted IL-10 and TGF-β secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4+CD25− T-cell formation

Η επίδραση της εφαρμογής των capital control στις οικονομικές καταστάσεις των εισηγμένων εταιριών που δραστηριοποιούνται στον κλάδο των κατασκευών

Ο κατασκευαστικός κλάδος στην Ελλάδα αποτέλεσε και αποτελεί τη «βαριά» βιομηχανία μιας χώρας που διάνυσε περιόδους ανάπτυξης αλλά παράλληλα και κρίσης. Η κατάρρευση του Κατασκευαστικού κλάδου αποτέλεσε τον βασικό πυλώνα ύπαρξης της πρόσφατης παγκόσμιας οικονομικής κρίσης. Η προβλεπτική ικανότητα της πορείας του κατασκευαστικού κλάδου μιας χώρας αποτελεί σημαντικό παράγοντα πρόληψης για την οικονομία της στο μέλλον. Προκειμένου να προβλεφθεί η πορεία του κατασκευαστικού κλάδου στη χώρα μας τα επόμενα χρόνια, απαιτείται η ανάλυση της πορείας του κλάδου σε προηγούμενες περιόδους. Για τον λόγο αυτό επιλέχθηκε η ως χρονική περίοδος έρευνας η πενταετία των capital controls 2015-2019 η οποία αναλογικά με την μετά Covid19 περίοδο έχει αρκετά κοινά χαρακτηριστικά . Στην έρευνα, παρουσιάζονται στοιχεία της Ελληνικής οικονομίας για το διάστημα 2015-2019 και στην συνέχεια εξετάζεται τον τρόπο με τον οποίο εισηγμένες εταιρίες στο Χρηματιστήριο Αθηνών διαχειρίστηκαν την επιβολή μέτρων βάση των καταστάσεών τους. Αναλύεται για τα έτη αυτά ο Κατασκευαστικός κλάδος στους 4 τομείς του, στις κατασκευές, στις μεταποιήσεις, στις τεχνικές μελέτες και στο Real Estate, μεμονωμένα αλλά και συγκριτικά, ενώ παρουσιάζονται συμπεράσματα και προβλέψεις για το μέλλον του κατασκευαστικού κλάδου στη χώρα μας.The construction industry in Greece was and is the "heavy" industry of a country that went through periods of development but also crisis. The collapse of the construction industry was the main pillar of the recent global financial crisis. The foresight of a country's construction industry is an important precautionary factor for its economy in the future. To predict the course of the construction industry in our country in the coming years, it is necessary to analyze the course of the industry in previous periods. For this reason, the five-year period of capital controls 2015-2019 was chosen as the research period, which in proportion to the post-Covid19 period has several common features. The research presents data of the Greek economy for the period 2015-2019 and then examines the way in which listed companies on the Athens Stock Exchange managed the imposition of measures based on their statements. The Construction sector is analyzed for these years in its 4 sectors, in construction, processing, technical studies and Real Estate, individually and comparatively, while conclusions and forecasts for the future of the construction sector in our country are presented

Modelling reaction time distribution in schizophrenia with Ratcliff’s Diffusion Model

Σε αρκετές έρευνες έχει παρατηρηθεί επιβράδυνση στην ταχύτητα απόκρισης σε ερεθίσματα σε ασθενείς με σχιζοφρένεια. Η παρούσα έρευνα στοχεύει στο να μοντελοποιήσει το χρόνο αντίδρασης μιας απλής δοκιμασίας απόφασης σε ασθενείς με σχιζοφρένεια και συγγενείς πρώτου βαθμού. Σκοπός ήταν να μπορέσουμε να εξάγουμε συμπεράσματα για το ποιες από τις παραμέτρους του μοντέλου σχετίζονται με γενετικά χαρακτηριστικά της ασθένειας και ποιες με συμπτώματα αυτής. Οι συμμετέχοντες του πειράματος διατέλεσαν μια δοκιμασία διπλής απόφασης και οι χρόνοι αντίδρασης αποσυντέθησαν στις παραμέτρους του Μοντέλου Διάχυσης του Ratcliff. Τα αποτελέσματα έδειξαν μείωση στην ταχύτητα συλλογής πληροφοριών (v) των ασθενών και των συγγενών αυτών σε σχέση με τους υγιείς. Επίσης, υπήρξε αύξηση στην παράμετρο του μοντέλου, που σχετίζεται με το μη-σχετικό με την απόφαση χρόνο (κωδικοποίηση ερεθίσματος και κινητική απόκριση, t0) στους ασθενείς. Τα αποτελέσματα αυτά μπορούν να παρέχουν αποδεικτικά στοιχεία για την κληρονομικότητα του ελλείμματος στην ταχύτητα συλλογής πληροφοριών στη σχιζοφρένεια, ενώ μπορούν να συσχετιστούν και με άλλες ασθένειες, όπως η ΔΕΠ-Υ (Διαταραχή Ελειμματικής Προσοχής – Υπερκινητικότητας).Slowing of processing speed is observed in patients with schizophrenia. The present study aimed to model RT distribution in a simple decision task in schizophrenia patients and their first-degree relatives to identify, which of the modelled processes, that are deviant in these patients, have state dependent and which trait dependent characteristics. Schizophrenia patients, siblings of patients and healthy controls performed a combined two-choice oddball, verbal n-back task and the RT distributions were modelled using the DDM model. RT model parameters were compared among patients, siblings and healthy controls. Use of the Drift Diffusion Model (DDM) showed a decrease in the speed of the basic decision process (diffusion drift rate (v)) in patients and relatives compared to controls. Also, an increase in the mean of the non-decisional processing time (t0) was present only for patients. These results could provide evidence for the heritability of the decrease in the speed of decision processing in schizophrenia that could be shared with other mental disorders such as Attention Deficit Hyperactivity Disorder

T-cell contact-dependent regulation of CC and CXC chemokine production in monocytes through differential involvement of NFκB: implications for rheumatoid arthritis

We and others have reported that rheumatoid arthritis (RA) synovial T cells can activate human monocytes/macrophages in a contact-dependent manner to induce the expression of inflammatory cytokines, including tumour necrosis factor alpha (TNFα). In the present study we demonstrate that RA synovial T cells without further activation can also induce monocyte CC and CXC chemokine production in a contact-dependent manner. The transcription factor NFκB is differentially involved in this process as CXC chemokines but not CC chemokines are inhibited after overexpression of IκBα, the natural inhibitor of NFκB. This effector function of RA synovial T cells is also shared by T cells activated with a cytokine cocktail containing IL-2, IL-6 and TNFα, but not T cells activated by anti-CD3 cross-linking that mimics TCR engagement. This study demonstrates for the first time that RA synovial T cells as well as cytokine-activated T cells are able to induce monocyte chemokine production in a contact-dependent manner and through NFκB-dependent and NFκB-independent mechanisms, in a process influenced by the phosphatidyl-inositol-3-kinase pathway. Moreover, this study provides further evidence that cytokine-activated T cells share aspects of their effector function with RA synovial T cells and that their targeting in the clinic has therapeutic potential

Dexamethasone induces ω3-derived immunoresolvents driving resolution of allergic airway inflammation.

To the Editor: Resolution of inflammation has long been considered to be a passive process that ensues in an inflammatory response following the dilution of proinflammatory cues. However, this paradigm is shifting as it is becoming increasingly evident that resolution is an active reaction that uses a complex molecular machinery that orderly terminates inflammation. Among the multiple mechanisms involved, specialized proresolving lipid mediators (SPMs) such as resolvins, protectins, and lipoxins have taken center stage.1 These are derived from ω3 and ω6 polyunsaturated fatty acids through complex intracellular and transcellular biosynthetic pathways, and promote resolution of inflammation by their manifold and concerted functions inhibiting leukocyte trafficking, dampening proinflammatory signaling, inducing apoptosis, and promoting anti-inflammatory M2-like macrophage phenotypes, efferocytosis, and tissue restitution.1This work was supported by core funding from the Hellenic Ministry of Education, Research and Religious Affairs and the Hellenic Ministry of Health, and by the research grants PREDICTA (contract no. 260895) from the European Commission, MIDAS (contract no. MIS 377047), and RESOLVE-ASTHMA (contract no. 2601) from the Hellenic Ministry of Education, Research and Religious Affairs

Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation.

Although specialized pro-resolving mediators (SPMs) biosynthesized from polyunsaturated fatty acids are critical for the resolution of acute inflammation, the molecules and pathways that induce their production remain elusive. Here, we show that TLR7, a receptor recognizing viral ssRNA and damaged self-RNA, mobilizes the docosahexaenoic acid (DHA)-derived biosynthetic pathways that lead to the generation of D-series SPMs. In mouse macrophages and human monocytes, TLR7 activation triggered production of DHA-derived monohydroxy metabolome markers and generation of protectin D1 (PD1) and resolvin D1 (RvD1). In mouse allergic airway inflammation, TLR7 activation enhanced production of DHA-derived SPMs including PD1 and accelerated the catabasis of Th2-mediated inflammation. D-series SPMs were critical for TLR7-mediated resolution of airway inflammation as this effect was lost in Alox15(-/-) mice, while resolution was enhanced after local administration of PD1 or RvD1. Together, our findings reveal a new previously unsuspected role of TLR7 in the generation of D-series SPMs and the resolution of allergic airway inflammation. They also identify TLR stimulation as a new approach to drive SPMs and resolution of inflammatory diseases