Ion channels in control of pancreatic stellate cell migration

Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all “hallmarks of cancer” such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs. Yet, there is growing evidence that ion channels in stromal cells also contribute to tumor progression. Here we investigated the function of K(Ca)3.1 channels in PSCs. K(Ca)3.1 channels are also found in many tumor cells of different origin. We revealed the functional expression of K(Ca)3.1 channels by means of Western blot, immunofluorescence and patch clamp analysis. The impact of K(Ca)3.1 channel activity on PSC function was determined with live-cell imaging and by measuring the intracellular Ca2(+) concentration ([Ca(2+)](i)). K(Ca)3.1 channel blockade or knockout prevents the stimulation of PSC migration and chemotaxis by reducing the [Ca(2+)](i) and calpain activity. K(Ca)3.1 channels functionally cooperate with TRPC3 channels that are upregulated in PDAC stroma. Knockdown of TRPC3 channels largely abolishes the impact of K(Ca)3.1 channels on PSC migration. In summary, our results clearly show that ion channels are crucial players in PSC physiology and pathophysiology

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

A Practical guide for non-financial companies when modeling longer-term currency and commodity exposures

12 page(s

Integration of Patient-Reported Outcome Data Collected Via Web Applications and Mobile Apps Into a Nation-Wide COVID-19 Research Platform Using Fast Healthcare Interoperability Resources: Development Study

BackgroundThe Network University Medicine projects are an important part of the German COVID-19 research infrastructure. They comprise 2 subprojects: COVID-19 Data Exchange (CODEX) and Coordination on Mobile Pandemic Apps Best Practice and Solution Sharing (COMPASS). CODEX provides a centralized and secure data storage platform for research data, whereas in COMPASS, expert panels were gathered to develop a reference app framework for capturing patient-reported outcomes (PROs) that can be used by any researcher. ObjectiveOur study aims to integrate the data collected with the COMPASS reference app framework into the central CODEX platform, so that they can be used by secondary researchers. Although both projects used the Fast Healthcare Interoperability Resources (FHIR) standard, it was not used in a way that data could be shared directly. Given the short time frame and the parallel developments within the CODEX platform, a pragmatic and robust solution for an interface component was required. MethodsWe have developed a means to facilitate and promote the use of the German Corona Consensus (GECCO) data set, a core data set for COVID-19 research in Germany. In this way, we ensured semantic interoperability for the app-collected PRO data with the COMPASS app. We also developed an interface component to sustain syntactic interoperability. ResultsThe use of different FHIR types by the COMPASS reference app framework (the general-purpose FHIR Questionnaire) and the CODEX platform (eg, Patient, Condition, and Observation) was found to be the most significant obstacle. Therefore, we developed an interface component that realigns the Questionnaire items with the corresponding items in the GECCO data set and provides the correct resources for the CODEX platform. We extended the existing COMPASS questionnaire editor with an import function for GECCO items, which also tags them for the interface component. This ensures syntactic interoperability and eases the reuse of the GECCO data set for researchers. ConclusionsThis paper shows how PRO data, which are collected across various studies conducted by different researchers, can be captured in a research-compatible way. This means that the data can be shared with a central research infrastructure and be reused by other researchers to gain more insights about COVID-19 and its sequelae

Microencapsulation as a tool to produce multicellular tumor spheroids

Storck J L, Homburg SV, Feldhans T, Bednarz H, Niehaus K, Patel A. Microencapsulation as a tool to produce multicellular tumor spheroids. In: Special Issue: ProcessNet‐Jahrestagung und 33. DECHEMA‐Jahrestagung der Biotechnologen 2018. Chemie Ingenieur Technik. Vol 90. Wiley; 2018: 1214-1214

Investigation of Low-Cost FDM-Printed Polymers for Elevated-Temperature Applications

Storck JL, Ehrmann G, Güth U, et al. Investigation of Low-Cost FDM-Printed Polymers for Elevated-Temperature Applications. Polymers. 2022;14(14): 2826.While fused deposition modeling (FDM) and other relatively inexpensive 3D printing methods are nowadays used in many applications, the possible areas of using FDM-printed objects are still limited due to mechanical and thermal constraints. Applications for space, e.g., for microsatellites, are restricted by the usually insufficient heat resistance of the typical FDM printing materials. Printing high-temperature polymers, on the other hand, necessitates special FDM printers, which are not always available. Here, we show investigations of common polymers, processible on low-cost FDM printers, under elevated temperatures of up to 160 °C for single treatments. The polymers with the highest dimensional stability and mechanical properties after different temperature treatments were periodically heat-treated between -40 °C and +80 °C in cycles of 90 min, similar to the temperature cycles a microsatellite in the low Earth orbit (LEO) experiences. While none of the materials under investigation fully maintains its dimensions and mechanical properties, filled poly(lactic acid) (PLA) filaments were found most suitable for applications under these thermal conditions

Appel et al 2018_supplemental material

Supplemental material for publication 'A potential role for GSK3beta in glucose-driven intrauterine catch-up growth in maternal obesity'

Data from: A potential role for GSK3beta in glucose-driven intrauterine catch-up growth in maternal obesity

Obesity and an unhealthy nutrition are on the rise and affect also women in childbearing age and hence, during pregnancy. Despite normal or even high birth weight the offspring suffers from long term metabolic risks. We hypothesized that fetal growth is disturbed during different intrauterine phases. Underlying molecular events remain elusive. Female mice were fed either a control diet (SD) or a high fat diet (HFD) after weaning until mating and during pregnancy. Pregnant mice were sacrificed at gestational time points G15.5 and G18.5 and fetuses and placentas were removed for analysis. HFD fetuses displayed intrauterine growth restriction (IUGR) at G15.5, which disappeared until G18.5, indicating an intrauterine catch-up growth during that time period. Main placental findings indicate decreased canonical Wnt-GSK3beta signaling and lower proliferation rates at G18.5 which goes along with a smaller placental transfer zone. On the other hand, glucose depots (glycogen cluster) in HFD placentas decreased stronger between G15.5 and G18.5 compared to placentas from SD mothers, and the glucose transporter protein GLUT-1 was increased at G18.5 in the HFD group. Maternal diet-induced obesity causes an IUGR phenotype at the beginning of the third week (G15.5) in our mouse model. This phenotype is reversed by the end of the third week (G18.5) despite of a smaller placental transfer zone, probably based on GSK3beta-mediated increased glucose mobilization in the placenta and hence an increased glucose supply to the fetus

A Potential Role for GSK3 beta in Glucose-Driven Intrauterine Catch-Up Growth in Maternal Obesity

Obesity and unhealthy nutrition are increasing and affect women of childbearing age and hence during pregnancy. Despite normal or even high birth weight, the offspring suffers from long-term metabolic risks. We hypothesized that fetal growth is disturbed during different intrauterine phases. Underlying molecular events remain elusive. Female mice were fed either a standard diet (SD) or a high-fat diet (HFD) after weaning until mating and during pregnancy. Pregnant mice were euthanized at gestational day (G) 15.5 and G18.5, and fetuses and placentas were removed for analysis. HFD fetuses displayed intrauterine growth restriction (IUGR) at G15.5, which disappeared until G18.5, indicating intrauterine catch-up growth during that time period. Main placental findings indicate decreased canonical Wnt-GSK3 beta signaling and lower proliferation rates at G18.5, which goes along with a smaller placental transfer zone. On the other hand, glucose depots (glycogen cluster) in HFD placentas decreased more strongly between G15.5 and G18.5 compared with placentas from SD mothers, and the glucose transporter protein GLUT-1 was increased at G18.5 in the HFD group. Maternal diet-induced obesity causes an IUGR phenotype at the beginning of the third week (G15.5) in our mouse model. This phenotype is reversed by the end of the third week (G18.5) despite a smaller placental transfer zone, probably based on GSK3 beta-mediated increased glucose mobilization in the placenta and hence an increased glucose supply to the fetus