Effects of a Secretin Receptor Antagonist on Cerebellar Learning

Eyeblink conditioning (EBC) is an important procedure used to understand the neuronal plasticity that occurs with learning and memory. Delay EBC requires a brainstem-cerebellar circuit while the role of the cerebellum in trace EBC is not as well understood because it requires a more complex neural circuitry involving regions of the medial prefrontal cortex and hippocampus. Secretin is a neuropeptide that is found in high concentrations within the cerebellum. Previous work has shown that blocking secretin’s effects in the cerebellum with intra-cerebellar infusion of relatively large volume of a secretin receptor antagonist impairs delay EBC (Fuchs et al. 2014). Here we study the effect that intra-cerebellar infusion of 0.5 μL secretin receptor antagonist (5-27 secretin) or vehicle prior to training sessions 1 and 2 has on delay and trace EBC in rats. A 600-ms tone CS was used for the delay EBC paradigm and a 300-ms tone CS followed by a 300-ms trace interval was used for the trace EBC paradigm. For delay EBC, the delay vehicle and antagonist groups displayed similar acquisition of conditioned responses (CRs). There was a trend for the trace antagonist group to underperform compared to the trace vehicle group though not quite at a significant level. One explanation for why the results for the delay EBC do not support previous work is that slow learning occurred in the delay vehicle group that may have prevented the effects of secretin receptor antagonist from reaching significance. The trend for the trace antagonist group to display decreased acquisition of CRs suggests that the cerebellum does play an important role in trace EBC. However, in order to better understand the neural circuitry involved in trace EBC, future work should analyze the role that cerebellar secretin itself has on trace EBC

From Natural Science to Philosophical Cosmology. On Function and Transformation of Metaphysics in 20th and 21st Century

Daß Metaphysik überhaupt noch eine Funktion habe, wurde seit dem 19. Jahrhundert von vielen Philosophen bestritten. Dabei ist der Begriff der Metaphysik vielschichtig. Er erschöpft sich keineswegs darin, ein letztbegründetes System zu entwickeln. Im vorliegenden Artikel wird er im Sinne einer philosophischen Kosmologie verstanden. Ausgangspunkt sind die Naturwissenschaften, die aufgrund ihrer Methode den Beobachter aus ihrem Bild der Welt ausschließen, das deshalb unvollständig bleiben muß. Die Aufgabe einer philosophischen Kosmologie ist es daher, die naturwissenschaftliche Interpretation der Wirklichkeit durch andere Sichtweisen der Natur zu ergänzen und diese untereinander zu verbinden. Der innere Zusammenhang der Wirklichkeit ebenso wie der der menschlichen Erfahrungen verbieten ein bloßes Nebeneinander von “Sprachspielen”. Eine philosophische Kosmologie entwickelt eine Sicht der Wirklichkeit, die ausgehend von den Naturwissenschaften und ihrer Methode auch den Beobachter in seiner Subjektivität und die durch sie bestimmten Relationen zur Welt umfaßt. Diese Anliegen hatte bereits Leibniz; im 20. Jahrhundert wurde es vor allem von Whitehead unter veränderten Bedingungen exemplarisch durchgeführt. Eine moderne Metaphysik vollzieht sich als ein letztlich unabschließbarer Prozeß der Synthese von allen dem Menschen zu einer bestimmten Zeit zugänglichen relevanten Erfahrungen.Since the 19th century many philosophers have argued, that metaphysics will have no more function at all. But the concept of metaphysics has many aspects. It must not only be understood as a system, based on everlasting principles. In the following article it is used in the sense of a philosophical cosmology. The startingpoint are the sciences, which exclude by their method the observer in his subjectivity; their view of the world must remain incomplete. Philosophical cosmology therefore has the task to complete the scientific interpretation of reality by other perspectives and to connect them with one another. The unity of reality as well as that of human experience forbids a side by side of different “Sprachspiele”. A philosophical cosmology therefore develops an interpretation of reality which embraces the scientific view of the world as well as the observer in his subjectivity and those relations, which are determined by it. Already Leibniz has tried to integrate both perspectives; in the 20th century, under new conditions, especially Whitehead has developed a philosopical cosmology. For a modern concept of metaphysics it is characteristic, that it is not a system, but a permanent process, in which all relevant experiences of man in a certain epoch are synthesized

Pro- and antiapoptotic events in Herpes simplex virus type 1 (HSV-1) infection of immature dendritic cells

Herpes simplex virus Typ 1 (HSV-1) ist ein humanpathogenes Virus der Familie Herpesviridae. Für eine erfolgreiche Virusreplikation besitzt HSV-1 mehrere Gene, die in den meisten infizierten Zelltypen Apoptose verhindern. Im Gegensatz dazu führt die HSV-1 Infektion eines zentralen Zelltyps des Immunsystems, den unreifen dendritischen Zellen (iDCs), zu Apoptose. Dies könnte ein Aspekt der HSV-1 Immunevasion sein. Bisher waren die Ursachen der Apoptose von HSV-1 infizierten iDCs unzureichend aufgeklärt. Es wurde jedoch gezeigt, dass das antiapoptotische zelluläre Protein c-FLIP in HSV-1 infizierten iDCs reduziert ist. In dieser Arbeit wurde die c-FLIP Menge in iDCs erstmalig mit Hilfe von RNA Interferenz erfolgreich reduziert. Dies bestätigte die Bedeutung von c-FLIP für die Lebensfähigkeit von iDCs. Folglich könnte auch die Reduktion der c-FLIP Menge nach HSV-1 Infektion iDCs für Apoptose empfindlich machen. Die HSV-1 induzierte c-FLIP Reduktion erfolgte in späten Stadien der Infektion, abhängig von der ordnungsgemäßen Expression viraler „early“ und „leaky late“ Gene. Sie fand nicht auf RNA Ebene statt und war unabhängig vom Proteasom und der Bindung an den „death inducing signaling complex“. Stattdessen wurde c-FLIP wahrscheinlich von einer viralen oder zellulären Protease abgebaut. In dieser Arbeit wurde erstmals gezeigt, dass zusätzlich zu Veränderungen im zellulären Apoptosesignalnetzwerk der Mangel an einem antiapoptotischen viralen Faktor zur Apoptose von HSV-1 infizierten iDCs beiträgt. Eine Microarray Analyse der HSV-1 Genexpression ergab, dass HSV-1 Latenz-assoziierte Transkripte (LATs) in apoptotischen iDCs signifikant geringer exprimiert waren als in nicht-apoptotischen epithelialen Zellen. LATs besitzen in Neuronen und epithelialen Zellen eine antiapoptotische Aktivität. Diese könnte den Mangel an c-FLIP kompensieren. Übereinstimmend mit dieser Hypothese induzierte eine HSV-1 LAT-Deletionsmutante mehr Apoptose in iDCs im Vergleich zum Wildtyp-Virus.Herpes simplex virus type 1 (HSV-1) is a human pathogen which belongs to the family Herpesviridae. HSV-1 encodes several genes, which serve to efficiently prevent apoptosis in most infected cell types, thereby ensuring successful virus replication. In contrast, HSV-1 infection of one central cell type of the immune system, immature dendritic cells (iDCs), results in apoptosis. This could be one aspect of HSV-1 immunevasion. So far, the mechanisms underlying apoptosis of HSV-1 infected iDCs were poorly defined. However, it has been shown that the antiapoptotic cellular protein c-FLIP is reduced in HSV-1 infected iDCs. In this work, the amount of c-FLIP was for the first time successfully reduced in iDCs by RNA interference. This confirmed the importance of c-FLIP for viability of iDCs. Therefore, it is likely that c-FLIP reduction after HSV-1 infection also sensitizes iDCs to apoptosis. HSV-1 induced c-FLIP reduction occurred at late stages of infection and was dependent on proper expression of early and leaky late virus genes. Furthermore, it was not operative at the RNA level and was independent from the proteasome and binding to the death inducing signaling complex. Rather, c-FLIP was presumably degraded by a viral or cellular protease. In this work it was shown for the first time, that in addition to changes in the cellular apoptosis signaling network, the lack of one antiapoptotic viral factor contributes to apoptosis of HSV-1 infected iDCs. HSV-1 latency-associated transcripts (LATs) were significantly lower expressed in apoptotic iDCs compared to non-apoptotic epithelial cells, determined by microarray analysis of HSV-1 gene expression. It is known that in neurons and epithelial cells, LATs possess a potent antiapoptotic activity. This could compensate the lack of c-FLIP. Consistent with this hypothesis, a LAT deletion mutant of HSV-1 induced more apoptosis in iDCs compared to the respective wild type virus

Post-combustion CO2 capture in coal-fired power plants: Comparison of integrated chemical absorption processes with piperazine promoted potassium carbonate and MEA

AbstractA thermodynamic and economic comparison of post-combustion CO2 capture processes using aqueous solutions of piperazine (PZ) promoted potassium carbonate (K2CO3) and monoethanolamine (MEA) based on fair boundary conditions and constant assumptions using rigorous thermodynamic models is described. In contrast to a first preliminary comparison, it is shown that under the stated assumptions and considered boundary conditions, a 7 m MEA solution performs better in both thermodynamic and economic terms than aqueous solutions of K2CO3 and PZ

Part Load Behaviour of Power Plants with a Retrofitted Post-combustion CO2 Capture Process

AbstractThe flexible and part load operation of fossil-fuelled power plants will increase due to the higher share of fluctuating renewable energies, like wind and solar power. In this work the part load behaviour of the post-combustion CO2 capture (PCC) process is evaluated. The net efficiency of the conventional hard-coal-fired power plant decreases from 45.6% at full load to 41.5% at 40% load. The net efficiency with PCC using 7 m MEA (monoethanolamine) as solvent decreases to 34.8% at full load and to 30.1% at 40% load. The pressure of the intermediate pressure/low pressure crossover section has major influence on the efficiency. In part load higher pressures are in advantage due to lower throttling losses. The shutdown of the PCC is a possibility to generate balancing power. A reduced capture rate of 75% leads to a generation of 5% additional power

Life threatening hypercalcemia: An unusual cause

Hypercalcemia is commonly seen in patients with primary hyperparathyroidism and malignancy. Rarely, it can be seen in adrenal insufficiency. We report a case of a 42 year old female who presented with altered mental status and weakness. The patient had decreased appetite, nausea and significant weight loss of 60 pounds in the last few months. Laboratory evaluation was significant for hypercalcemia (15 mg/ dL) and acute kidney injury (1.5 mg/ dL). Work up for malignancy and hyperparathyroidism was negative. She was diagnosed with adrenal insufficiency based on cortisol levels prior to steroids of \u3c 0.5 mcg/ dL. She was treated with steroids and her hypercalcemia resolved within two days of steroids. This case shows that adrenal insufficiency may present as hypercalcemia and acute kidney injury. It should be considered as a potential cause while evaluating a patient for hypercalcemia.https://scholarlycommons.henryford.com/merf2020caserpt/1008/thumbnail.jp