Differential requirement of bone morphogenetic protein receptors Ia (ALK3) and Ib (ALK6) in early embryonic patterning and neural crest development

Background Bone morphogenetic proteins regulate multiple processes in embryonic development, including early dorso-ventral patterning and neural crest development. BMPs activate heteromeric receptor complexes consisting of type I and type II receptor-serine/threonine kinases. BMP receptors Ia and Ib, also known as ALK3 and ALK6 respectively, are the most common type I receptors that likely mediate most BMP signaling events. Since early expression patterns and functions in Xenopus laevis development have not been described, we have addressed these questions in the present study. Results Here we have analyzed the temporal and spatial expression patterns of ALK3 and ALK6; we have also carried out loss-of-function studies to define the function of these receptors in early Xenopus development. We detected both redundant and non-redundant roles of ALK3 and ALK6 in dorso-ventral patterning. From late gastrula stages onwards, their expression patterns diverged, which correlated with a specific, non-redundant requirement of ALK6 in post-gastrula neural crest cells. ALK6 was essential for induction of neural crest cell fate and further development of the neural crest and its derivatives. Conclusions ALK3 and ALK6 both contribute to the gene regulatory network that regulates dorso-ventral patterning; they play partially overlapping and partially non-redundant roles in this process. ALK3 and ALK6 are independently required for the spatially restricted activation of BMP signaling and msx2 upregulation at the neural plate border, whereas in post-gastrula development ALK6 exerts a highly specific, conserved function in neural crest development

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Masteroppgave Grafisk design og illustrasjon, Avdeling Desig

Nutrition Education in U.S. Medical Schools: A History and Proposal for the Future

Background: Obesity and obesity related chronic diseases such as cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and hypertension (HTN) continue to be significant health crises in the United States. Patients largely rely on physicians, not Registered Dietitians (RDs), for the bulk of nutrition-related information. Yet, physicians consistently rate their nutritional counseling skills as poor and have little confidence in their abilities. The lack of nutrition and nutritional counseling in medical school curriculum does not support physicians’ responsibility in addressing obesity and obesity-related chronic disease. Objective: Evaluate to what extent nutrition has been incorporated into medical school curriculum in the past and today; investigate barriers to a more extensive nutrition curriculum; review possibilities for furthering nutrition education into the medical school setting. Design: Narrative review Results: The average hours of nutrition education in medical schools has remained stagnant at an average of 19-22 hours. Increasingly, nutrition education is moving from separate, stand-alone classes towards integration in existing curriculum. Physicians consistently rate their knowledge of and skills in nutrition and nutrition counseling as poor. Physicians recognize their weakness in nutrition, but many barriers stand in the way of nutrition education incorporation. Conclusions: Because hours of nutrition education have remained stagnant for the past 58 years, incorporating nutrition education into existing curriculum with a focus on interdisciplinary learning appears to be the new strategy to increase net nutrition exposure hours. However, absence of nutrition accreditation requirements is the root of the knowledge and skill gap. Advocacy for national nutrition accreditation requirements is essential to foster nutrition-inclusive, integrated curricula.Master of Public Healt

Studien zur Verwendung von Polyelektrolyten und Polymediatoren in der organischen Elektrosynthese

Im Zusammenhang mit dem Trennungsproblem, das sich aus der Verwendung von Leitsalzen und Mediatoren ergibt, wurde die Anwendbarkeit löslicher Polyelektrolyte und Polymediatoren untersucht. Anhand der TEMPO-vermittelten Umsetzung von Alkoholen in Carbonylverbindungen als Modellreaktion wurde demonstriert, dass Polymethacrylateihren den Zweck effizient erfüllen können. Die Alkoholoxidation ist auch im präparativen Maßstab hocheffizient, wobei der Ansatz auf Polymerbasis die Trennung von Mediator und Leitsalz in einem einzigen Membranfiltrationsschritt ermöglicht

Complement Receptor 3 and its role in the interaction of primary human macrophages with apoptotic Leishmania major promastigotes

Leishmania parasites are the causative agent of the neglected tropical disease leishmaniasis. The sand fly vector-borne, disease-initiating Leishmania promastigote life stage (Lm) is comprised of viable and apoptotic parasites. Targeting of the latter by LC3-associated phagocytosis (LAP) leads to a decreased activation of the adaptive immune system. Based on these findings, this study focuses on (1) the internalization of apoptotic Lm by human monocyte-derived pro- (hMDM1) and anti-inflammatory (hMDM2) macrophages, (2) evasion of viable Lm from degradation as well as (3) identification and (4) functional characterization of factors that lead to uptake of apoptotic Lm and LAP induction. For detailed analysis of the apoptotic Lm population we separated viable from apoptotic Lm. Phagocytosis assays by flow cytometry in which hMDMs were differentially infected with viable or apoptotic Lm showed that hMDMs ingested apoptotic Lm more rapidly than viable parasites. Investigations of supernatants from differentially infected hMDMs and hMDDCs by ELISA revealed not only a higher release of the anti-inflammatory cytokine IL-10 but also an increase in secretion of the pro-inflammatory cytokines IL-1β, IL-6 and IL-8 in presence of apoptotic Lm. Live cell microscopy showed that LAP can be triggered by viable and apoptotic Lm. Phagosomes harboring apoptotic parasites were targeted more frequently and more rapidly by eGFP-LC3 in hMDM2 as compared to phagosomes containing viable parasites. To identify factors that initiate apoptotic parasite internalization and LC3 recruitment, magnetic isolation of apoptotic Lm-containing phagosomes was performed. Subsequent mass spectrometry and data analysis revealed the phagocytic receptors low-density lipoprotein receptor-related protein 1 (CD91) and Complement Receptor 3 (CR3) to be highly abundant in phagosomes harboring apoptotic Lm. Blocking of CD91 with a monoclonal antibody was not efficient and knockdown of CD91 with siRNA did not affect uptake of Lm, but the interaction still might be relevant and should be investigated in more detail. Inhibition of CR3 with a functional antibody significantly reduced uptake of apoptotic Lm by hMDMs. This receptor blocking in turn resulted in a decreased production of pro-inflammatory TNF-α by hMDM1 and a significantly diminished IL-10 secretion by hMDM2. Inhibition of CR3 strikingly reduced LC3 lipidation as a measure for LAP induction in hMDM2 challenged with apoptotic or stationary phase Lm. Intriguingly, decreased internalization of apoptotic Lm neither resulted in a higher T cell proliferation nor in an increased survival of viable Lm within hMDMs. In conclusion, the data for the first time describe CR3 to play a significant role in the interaction of hMDM2 with especially apoptotic Lm and indicate a role of the receptor in LAP. Control of receptor-mediated internalization and LAP of apoptotic Lm could serve as a novel therapeutic approach to combat the neglected tropical disease leishmaniasis.Parasiten der Gattung Leishmania sind die Erreger der vernachlässigten Tropenkrankheit Leishmaniose. Das durch einen Sandfliegenvektor übertragene promastigote Lebensstadium der Leishmanien (Lm) umfasst lebendige als auch apoptotische Parasiten. Aufnahme der Letzteren durch LC3-assoziierte Phagozytose (LAP) führt zu einer verminderten Aktivierung des adaptiven Immunsystems. Basierend auf diesen Erkenntnissen konzentriert sich die vorliegende Studie auf (1) die Internalisierung von apoptotischen Lm durch primäre, humane pro- (hMDM1) und anti-inflammatorische (hMDM2) Makrophagen, (2) das Entkommen der lebendigen Parasiten vor der Degradation in der Zelle sowie (3) die Identifizierung und (4) funktionelle Charakterisierung von Faktoren, die zur Aufnahme der apoptotischen Lm und einer Induktion von LAP führen. Für eine detaillierte Analyse der apoptotischen Parasiten wurden diese von lebendigen Lm getrennt. Phagozytose-Assays mittels Durchflusszytometrie zeigten, dass nach differenzieller Infektion von hMDMs mit apoptotischen und lebendigen Lm die Aufnahme apoptotischer Lm schneller erfolgte als die Aufnahme lebendiger Parasiten. Untersuchungen von Zellüberständen differentiell infizierter hMDMs und hMDDCs mittels ELISA zeigten nicht nur eine erhöhte Freisetzung des anti-inflammatorischen Zytokins IL-10, sondern auch eine Erhöhung der Sekretion der pro-inflammatorischen Zytokine IL-1β, IL-6 und IL-8 durch hMDMs in Gegenwart von apoptotischen Lm. Die Analyse der LAP von Lm mittels Lebendzell-Mikroskopie ergab, dass eGFP-LC3 in hMDM2 in größerem Maße und schneller zu Phagosomen rekrutiert wurde, die apoptotische Parasiten beinhalteten, als zu Phagosomen, die lebendige Parasiten enthielten. Um Faktoren zu identifizieren, die die Internalisierung der apoptotischen Parasiten und die Rekrutierung von LC3 auslösen, wurde eine magnetische Isolierung von apoptotischen Lm-enthaltenden Phagosomen durchgeführt. Markierungsfreie Massenspektrometrie und eine anschließende Datenanalyse zeigten, dass die Phagozytoserezeptoren Lipoprotein receptor-related protein 1 (CD91) und Complement Receptor 3 (CR3), in Phagosomen mit apoptotischem Lm in großer Zahl vorhanden waren. Die Blockierung von CD91 mit einem monoklonalen Antikörper war nicht effizient und auch der Knockdown des Rezeptors hatte keinen Einfluss auf die Wechselwirkung mit Lm. Die Inhibierung von CR3 mit einem funktionellen Antikörper hingegen reduzierte signifikant die Wechselwirkung von hMDMs mit apoptotischem Lm. Diese Blockierung des Rezeptors führte wiederum zu einer verminderten Produktion von pro-inflammatorischem TNF-α durch hMDM1 und einer signifikant verminderten anti-inflammatorischen IL-10-Sekretion durch hMDM2. Zusätzlich verringerte die Inhibierung von CR3 die LC3-Konversion in hMDM2, welche mit apoptotischen oder stationäre Phase-Lm inkubiert wurden. Interessanterweise führte eine verringerte Internalisierung von apoptotischen Lm weder zu einer höheren T-Zell-Proliferation noch zu einem erhöhten Überleben lebendiger Lm in infizierten hMDMs. Zusammenfassend zeigen diese Daten zum ersten Mal, dass Complement Receptor 3 eine signifikante Rolle in der Wechselwirkung von hMDM2 mit apoptotischen Lm spielt und lassen zudem auf eine Rolle des Rezeptors in LAP schließen. Rezeptor-vermittelte Internalisierung und LAP von apoptotischen Lm könnte als neuer therapeutischer Ansatz zur Bekämpfung der vernachlässigten Tropenkrankheit Leishmaniose dienen

Identitet - makt & tillit - endring : skoleledelse synliggjort ved tre aspekter

Hva er en god skole? Hvordan blir gode skoler gode? Blir gode skoler gode fordi de har gode ledere? Hvis vi antar at skoler blir gode fordi de blir ledet av gode ledere, hva særpreger i så fall denne lederen og den praksis hun utøver? Med utgangspunkt i disse spørsmålene blir vår problemstilling: Hvordan kommer ledelse til uttrykk ved skoler som har høstet anerkjennelse fra myndighetene. Denne oppgaven handler skoleledelse og den handler om tre aspekter ved synliggjort skoleledelse. Det er aspekter ved skoleledelse slik det kom til uttrykk ved en bonusskole, Lillevann. Disse tre aspektene framkom ved at rektor ved denne skolen fortalt sin historie om sin yrkesutvikling og yrkesutøvelse. Hennes fortelling ble kontekstualisert av andre aktører. De tre aspektene ved ledelse på en skole som har høstet anerkjennelse fra myndighetene dreier seg om identitet, makt og tillit og endring. Når det snakkes om tre ledelsesaspekter og hvordan de blir uttrykt i denne oppgaven, er det måten rektor utøver og reflekterer ledelse på. Oppgaven knyttes derfor til den formelle lederen på skolen. Av våre tre informanter har vi valgt å bruke rektor som hovedinformant. Det er hennes stemme som høres, de andre to informantene brukes til å utfylle og belyse det rektor sier. Analysen ved Grounded Theory ga oss de tre aspektene som vi setter søkelyset på. Vi ønsker å vekte disse tre områdene relativt likt. Vi ønsker å belyse at ledelse i skoler handler om både lederen som person, lederen som del av en organisasjon og lederen som innovatør. Vår oppgave er en empirinær oppgave, og fokusområdene er framkommet ved en induktiv/ deduktiv metode. I et eget metodekapittel vil vi gå nærmere inn på denne, og beskrive den benyttede analysemetoden, Grounded Theory, og hvordan vi anvendte denne. Masteroppgaven er knyttet til SOL-prosjektet (Skole og ledelse) i den forstand at vi brukte de samme utvalgskriteriene som dette prosjektet. I tillegg til dette bruker vi SOLs definisjoner på ledelse. I disse kriteriene inngår både bonus- og demonstrasjonsskoler. Vi kommer tilbake til både SOL-prosjektet og bonus- og demonstrasjonsskoler i egne kapitler. Som praktikere i forskningsfeltet er det viktig og vanskelig å skille yrkesrollen fra rollen som student og forsker. Vi er begge rektorer med inngående kjennskap til informantenes hverdag. Det var mange ganger svært lett å identifisere seg med det informantene fortalte i stedet for å sitte på ”glasstaket” og være objektiv i datainnhentingen. En annen begrensing i oppgaven er at vi benytter få informanter og bare en skole for datainnsamlingen. Vi vil argumentere for dette i kapitlet om metode. I metodekapitlet vil vi også redegjøre for kvalitativ forskningstradisjon, intervju og analyse ved GT, som tidligere nevnt. Etter metodekapitlet følger en del der det redegjøres for ulike sider ved identitet, makt og tillit og endring ut fra et teoretisk perspektiv, og til slutt presenteres studiens empiri. Oppgaven avsluttes med en drøfting av vår empiri i lys av den benyttede teori. I tillegg vil avslutningen av oppgaven inneholde en beskrivelse av vår egen prosess og læring