Phorbol-12-myristate-13-acetate is a potent enhancer of B cells with a granzyme B+ regulatory phenotype

IntroductionThe infusion of ex-vivo-generated regulatory B cells may represent a promising novel therapeutic approach for a variety of autoimmune and hyperinflammatory conditions including graft-versus-host disease.MethodsPreviously, we developed a protocol for the generation of a novel population of regulatory B cells, which are characterized by secretion of enzymatically active granzyme B (GraB cells). This protocol uses recombinant interleukin 21 (IL-21) and goat-derived F(ab)’2 fragments against the human B cell receptor (anti-BCR). Generally, the use of xenogeneic material for the manufacturing of advanced therapy medicinal products should be avoided to prevent adverse immune reactions as well as potential transmission of so far unknown diseases.ResultsIn the present work we demonstrated that phorbol-12-myristate-13-acetate (PMA/TPA), a phorbol ester with a particular analogy to the second messenger diacylglycerol (DAG), is a potent enhancer of IL-21-induced differentiation of pre-activated B cells into GraB cells. The percentage of GraB cells after stimulation of pre-activated B cells with IL-21 and PMA/TPA was not significantly lower compared to stimulation with IL-21 and anti-BCR.DiscussionGiven that PMA/TPA has already undergone encouraging clinical testing in patients with certain haematological diseases, our results suggest that PMA/TPA may be a safe and feasible alternative for ex-vivo manufacturing of GraB cells

Prediction of Glioblastoma Multiform Response to Bevacizumab Treatment Using Multi-Parametric MRI

Glioblastoma multiform (GBM) is a highly malignant brain tumor. Bevacizumab is a recent therapy for stopping tumor growth and even shrinking tumor through inhibition of vascular development (angiogenesis). This paper presents a non-invasive approach based on image analysis of multi-parametric magnetic resonance images (MRI) to predict response of GBM to this treatment. The resulting prediction system has potential to be used by physicians to optimize treatment plans of the GBM patients. The proposed method applies signal decomposition and histogram analysis methods to extract statistical features from Gd-enhanced regions of tumor that quantify its microstructural characteristics. MRI studies of 12 patients at multiple time points before and up to four months after treatment are used in this work. Changes in the Gd-enhancement as well as necrosis and edema after treatment are used to evaluate the response. Leave-one-out cross validation method is applied to evaluate prediction quality of the models. Predictive models developed in this work have large regression coefficients (maximum R2 = 0.95) indicating their capability to predict response to therapy

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Comparative evaluation of macrohemodynamic parameters in perioperative algorithms of the goal-directed therapy

In dieser Studie wurden Algorithmen der perioperativen hämodynamischen zielgerichteten Therapie miteinander verglichen. Anhand perioperativ erhobener hämodynamischer Daten von abdominal- und thoraxchirurgischen Patienten wurde untersucht, welche Konsequenzen sich bei der Wahl eines Algorithmus für den Patienten ergeben würden. Dabei zeigten sich erhebliche Unterschiede in den Interventionshäufigkeiten. Bei fehlender Evidenz für die Überlegenheit eines Algorithmus gegenüber anderen, sollten bei der Wahl eines Algorithmus therapeutische und wirtschaftliche Konsequenzen berücksichtigt werden.In this study we compared for the first time some perioperative algorithms of hemodynamic goal-directed therapy. Based on the perioperative hemodynamic data of abdominal and thoracic surgical patients we examined which consequences the patient would face depending on the chosen algorithm. The results show significant differences in the intervention rates. Because advantages of one specific algorithm over the other is not evident the therapeutic and economic consequences should be considered when choosing an algorithm for perioperative goal-directed therapy

Women of Middletown : a compilation and review : an honors thesis (HONRS 499)

There is no abstract available for this thesisHonors CollegeThesis (B.?.

Women of Middletown : a compilation and review : an honors thesis (HONRS 499)

There is no abstract available for this thesisThesis (B.?.)Honors Colleg

Cycling Behavior and Memory Formation

Circadian research has spent considerable effort in the determining clock output pathways, including identifying both physiological and behavioral processes that demonstrate significant time-of-day variation. Memory formation and consolidation represent notable processes shaped by endogenous circadian oscillators. To date, very few studies on memory mechanisms have considered potential confounding effects of time-of-day and the organism's innate activity cycles (e.g., nocturnal, diurnal, or crepuscular). The following studies highlight recent work describing this interactive role of circadian rhythms and memory formation, and were presented at a mini-symposium at the 2009 annual meeting of the Society for Neuroscience. The studies illustrate these time-of-day observations in a variety of behavioral paradigms and model organisms, including olfactory avoidance conditioning in Drosophila , long-term sensitization in Aplysia , active-avoidance conditioning in Zebrafish, and classical fear conditioning in rodents, suggesting that the circadian influence on memory behavior is highly conserved across species. Evidence also exists for a conserved mechanistic relationship between specific cycling molecules and memory formation, and the extent to which proper circadian cycling of these molecules is necessary for optimal cognitive performance. Studies describe the involvement of the core clock gene period , as well as vasoactive intestinal peptide, melatonin, and the cAMP/MAPK (cAMP/mitogen-activated protein kinase) cascade. Finally, studies in humans describe evidence for alterations in cognitive performance based on an interaction between sleep–wake homeostasis and the internal circadian clock. Conservation of a functional relationship between circadian rhythms with learning and memory formation across species provides a critical framework for future analysis of molecular mechanisms underlying complex behavior

Masterprojekt Zweitwohnsitz im alpinen Raum. Gesamtbericht WS 2020/21

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