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Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in the acute phase of ischemic stroke and highlight accompanying changes in immune cells and S1P receptors (S1PR). Using a C57BL/6 mouse model of middle cerebral artery occlusion (MCAO), we assessed S1P concentrations in the brain, plasma, and spleen. We found a steep S1P gradient from the spleen towards the brain. Results obtained by qPCR suggested that cells expressing the S1PR type 1 (S1P1+) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (TH) and regulatory T (TREG) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1PR expression patterns in the brain after MCAO. This study provides insight that the S1P-S1PR axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1PR+ TH and TREG cells. Further insights by which means the S1P-S1PR-axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.
Das Ziel dieser Arbeit ist, einen Text automatisch darauf zu untersuchen, ob er Gebäude beschreibt, und diese gegebenenfalls zu visualisieren. Zu diesem Zweck wurde ein Prototyp entwickelt, der mithilfe von NLP-Software auf Basis einer UIMA-Pipeline einen Text auf Gebäudedaten untersucht und diese anschließend als 3D-Modelle auf einer Karte visualisiert. Um die Güte des Projekts zu bestimmen wurde eine Evaluation durchgeführt, in der die Aufgabe darin bestand, Paragraphen ihren zugehörigen 3D-Modellen zuzuordnen. Die Ergebnisse wiesen eine Erkennungsrate von 88.67\% auf. Jedoch wurden auch Schwächen im Standardisierungsverfahren der Parameter und in der einseitigen Art zu Visualisieren aufgezeigt. Zum Schluss wird vorgestellt, wie diese Schwachstellen mithilfe eines ontologischen Modells behoben werden können und wie mit dem Projekt weiterverfahren werden kann.
Diese Arbeit etabliert eine nicht-invasive, volloptische Methode zur in-vivo Beobachtung des Membranpotentials in erregbaren Zellen des Fadenwurms C. elegans, die als Ersatz oder komplementär zu invasiven, elektrophysiologischen Methoden verwendet werden kann.
This article presents a case study of three different coin series (RRC 468-RRC 470) minted near contemporaneously in Hispania during the latter stages of the civil war, which present strikingly different representations of foreign peoples and places. While Caesar’s coin series (RRC 468) displays an image of submissive Gallic captives and a military trophy, Cnaeus Pompey Jr’s two series (RRC 469=470) feature personifications of the region and local cities and depicts them working together with their Pompeian counterpart in the pursuit of victory in the area. The article incorporates hoard evidence to further develop our understanding of how a contemporary viewer might have experienced these contrasting images of foreign peoples and places. It demonstrates which would have been the more common image in circulation and provides evidence for potential audience targeting with the Pompeian coin series. In light of recent scrutiny of Pompeian patronage networks in Spain, this hoard evidence for potential audience targeting allows a new interpretation of the Pompeian coin series as targeting a potentially wavering host community to be put forward.
Background: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA.
Methods: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. Primary outcome measure: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo.
Results: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation.
Conclusion: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA.
Trial registration: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov
SARS-CoV-2 is the causative agent of COVID-19. Severe COVID-19 disease has been associated with disseminated intravascular coagulation and thrombosis, but the mechanisms underlying COVID-19-related coagulopathy remain unknown. The risk of severe COVID-19 disease is higher in males than in females and increases with age. To identify gene products that may contribute to COVID-19-related coagulopathy, we analyzed the expression of genes associated with the Gene Ontology (GO) term “blood coagulation” in the Genotype-Tissue Expression (GTEx) database and identified four procoagulants, whose expression is higher in males and increases with age (ADAMTS13, F11, HGFAC, KLKB1), and two anticoagulants, whose expression is higher in females and decreases with age (C1QTNF1, SERPINA5). However, the expression of none of these genes was regulated in a proteomics dataset of SARS-CoV-2-infected cells and none of the proteins have been identified as a binding partner of SARS-CoV-2 proteins. Hence, they may rather generally predispose individuals to thrombosis without directly contributing to COVID-19-related coagulopathy. In contrast, the expression of the procoagulant transferrin (not associated to the GO term “blood coagulation”) was higher in males, increased with age, and was upregulated upon SARS-CoV-2 infection. Hence, transferrin warrants further examination in ongoing clinic-pathological investigations.
miR-142-3p expression is predictive for severe traumatic brain injury (TBI) in trauma patients
(2020)
Background: Predictive biomarkers in biofluids are the most commonly used diagnostic method, but established markers in trauma diagnostics lack accuracy. This study investigates promisingmicroRNAs(miRNA)releasedfromaffectedtissueafterseveretraumathathavepredictive values for the effects of the injury.
Methods: A retrospective analysis of prospectively collected data and blood samples of n = 33 trauma patients (ISS≥16) is provided. Levels of miR-9-5p, -124-3p, -142-3p, -219a-5p, -338-3pand-423-3p inseverelyinjuredpatients (PT)withouttraumatic braininjury (TBI) or with severe TBI (PT + TBI) and patients with isolated TBI (isTBI) were measured within 6 h after trauma.
Results: The highest miR-423-3p expression was detected in patients with severe isTBI, followed by patients with PT + TBI, and lowest levels were found in PT patients without TBI (2−∆∆Ct,p = 0.009). ApositivecorrelationbetweenmiR-423-3plevelandincreasingAIShead (p = 0.001) and risk of mortality (RISC II, p = 0.062) in trauma patients (n = 33) was found. ROC analysis of miR-423-3p levels revealed them as statistically significant to predict the severity of brain injury in trauma patients (p = 0.006). miR-124-3p was only found in patients with severe TBI, miR-338-3p was shown in all trauma groups. miR-9-5p, miR-142-3p and miR-219a-5p could not be detected in any of the four groups. Conclusion: miR-423-3p expression is significantly elevated after isolated traumatic braininjuryandpredictableforsevereTBIinthefirsthoursaftertrauma. miR-423-3pcouldrepresent a promising new biomarker to identify severe isolated TBI.
A message from the human placenta: structural and immunomodulatory defense against SARS-CoV-2
(2020)
The outbreak of the coronavirus disease 2019 (COVID-19) pandemic has caused a global public health crisis. Viral infections may predispose pregnant women to a higher rate of pregnancy complications, including preterm births, miscarriage and stillbirth. Despite reports of neonatal COVID-19, definitive proof of vertical transmission is still lacking. In this review, we summarize studies regarding the potential evidence for transplacental transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterize the expression of its receptors and proteases, describe the placental pathology and analyze virus-host interactions at the maternal-fetal interface. We focus on the syncytium, the barrier between mother and fetus, and describe in detail its physical andstructuraldefenseagainstviralinfections. Wefurtherdiscussthepotentialmolecularmechanisms, whereby the placenta serves as a defense front against pathogens by regulating the interferon type III signaling, microRNA-triggered autophagy and the nuclear factor-κB pathway. Based on these data, we conclude that vertical transmission may occur but rare, ascribed to the potent physical barrier, the fine-regulatedplacentalimmunedefenseandmodulationstrategies. Particularly,immunomodulatory mechanismsemployedbytheplacentamaymitigateviolentimmuneresponse,maybesoftencytokine storm tightly associated with severely ill COVID-19 patients, possibly minimizing cell and tissue damages, and potentially reducing SARS-CoV-2 transmission.