Diversity of value-determining compounds in Daucus carota L.

Es wurden 100 Genotypen (Sorten) Kulturmöhren und 104 Genotypen Wildmöhren auf die Carotinoide alpha- und beta-Carotin, Lycopin und Lutein sowie auf die Polyacetylene Falcarinol, Falcarindiol und Falcarindiol-3-Acetat untersucht. Für die – wirtschaftlich sinnvolle - gleichzeitige Extraktion der Carotinoide und Polyacetylene aus den Karotten wurde ein neues Verfahren entwickelt. Durch beschleunigte Lösungsmittelextraktion (ASE) aus gefriergetrocknetem Karottenpulver wurden in einer ersten und einzigen Extraktion etwa 60 % bis 70 % der gesuchten Inhaltsstoffe aus der Probe gelöst. Damit ist das neu entwickelte Extraktionsverfahren gegenüber herkömmlichen Verfahren der Extraktion von Carotinoiden und Polyacetylenen aus Karotten um ein Mehrfaches schneller und effizienter. Polyacetylene konnten in signifikanter Konzentration nicht nur in Wildmöhren gemessen werden. Ein Zusammenhang zwischen hohen Polyacetylenkonzentrationen und hohen Zuckergehalten konnte in Kulturmöhren festgestellt werden. Die Gehalte an Carotinoiden und Polyacetylenen sind in Kulturmöhren im Wesentlichen sortenspezifisch und kaum von äußeren Bedingungen abhängig. Auch die unterschiedlichen Reaktionen der verschiedenen Genotypen auf die konkreten Standortbedingungen sind maßgeblich genetisch determiniert. Eine Korrelation zwischen den flüchtigen Inhaltsstoffen des Blattwerks der untersuchten Kulturmöhren und den untersuchten nicht-flüchtigen Inhaltsstoffen der Wurzeln besteht nicht. Ein Schnelltest des Blattwerks für Vorernteuntersuchungen von Karottenwurzeln kann daher nicht entwickelt werden. Ontogeneseversuche an je zwei Genotypen Wild- und Kulturmöhren bestätigten den maßgeblichen Einfluss der genetischen Disposition auf Zeitpunkt und Ausmaß der Bildung von Carotinoiden und Polyacetylenen. Bei Kulturmöhren zeigte Kältestress demgegenüber keine signifikanten Auswirkungen auf den Gehalt der untersuchten Carotinoide und Polyacetylene.The content of the non-volatile compounds in carrot including carotenoids, polyacetylenes and sugars were screened in 100 genotypes of cultivated carrots and 104 genotypes of wild carrots. Carotenoids included alpha- and beta-carotene as well as lutein and lycopene. As key compounds of the polyacetylenegroup falcarinol (FaOH), falcarindiol (FaDOH) and falcarindiol-3-acetate (FaDOH-3-acetate) were detected. For simultaneous extraction of the non-volatile carotenoids and polyacetylenes a new accelerated extraction method was developed. Using accelerated solvent extraction (ASE), 60 % to 70 % of carotenoids and polyacetylenes could be simultaneously extracted from lyophilised carrot powder during the first extraction. For this reason this newly developed extraction process linked with a fast HPLC-DAD and HPLC-MS analysis is faster and more efficient than the established methods. Significant polyacetylene contents were detected not only in wild carrot genotypes but also in the cultivated carrots. A positive correlation between polyacetylenes and sucrose contents in cultivated carrots could be detected. The carotenoid and polyacetylene contents in cultivated carrots are mostly influenced by the genetic background of the plant; environmental factors have only minor influence. In this study it was found that the genetic background has the main influence on the contents of the non-volatile compounds in the carrots in contrast to the influence of the growing place. An analysis of the volatile and non-volatile compounds in the roots of 100 cultivated carrot genotypes showed that there is no correlation between volatile and non-volatile compounds in the carrot root. Therefore, a rapid test for early selection of carrot roots is not possible. Ontogenesis studies confirmed the thesis that the content of carotenoids and polyacetylenes is mainly genetically controlled. An influence of cold stress on the contents of non-volatile compounds in cultivated carrots has not been found

Decline in seasonal influenza vaccine effectiveness with vaccination program maturation: A systematic review and meta-analysis

ObjectivesEvidence suggests repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (number of years since program inception) [PM] as proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies.MethodsWe systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles, and calculated pooled VE using an inverse variance, random effects model. The primary outcome was pooled VE against all influenza.ResultsWe included 72 articles from 11,931 unique citations. Across the three categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2) and influenza B.ConclusionsThe evidence suggests influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE

Etude de l'interaction du virus de l'hépatite C sur les cellules plasmacytoides dendritiques

Les pDCs répondent aux infections virales par la production d'IFN-α. L'élimination du virus de l'hépatite C (VHC) chez plus de 50% des patients infectés par le traitement à l'IFN-alpha suggère que les pDCs jouent un rôle majeur dans le contrôle de l'infection VHC. Les pDCs exposées aux hépatocytes infectés par VHC, produisent beaucoup d'IFN-α. Néanmoins, en dépit de cette production par TLR7 par les pDCs, VHC continue à se répliquer dans le foie infecté. J'ai approfondi les connaissances des mécanismes moléculaires d'exploration des particules de VHC et des cellules infectées par le VHC par les pDCs. J'ai ciblé ma recherche sur le contact des particules de VHC avec la surface des pDCs, sur la voie de signalisation de déclenchée, sur leur effet sur la production des IFNs et des cytokines proinflammatoires et sur la différenciation cellulaire. Nos résultats suggèrent que le virus associé aux cellules signalise dans les pDCs via un mécanisme dépendant de l'endocytose et d'IRF7 mais pas de la voie NF-κB. En dépit de l'induction d'IFN-α, le VHC associé aux hépatocytes n'induit une réponse pleinement fonctionnelle des pDCs. Les particules virales de VHC inhibent, via la fixation de la glycoprotéine E2 aux CLRs, la production d'IFN-α et d'IFN-λ dans les pDCs exposées aux hépatocytes infectés par VHC et induisent dans les pDCs, une phosphorylation rapide d'Akt et Erk1/2, d'une manière similaire au crosslinking de BDCA-2 ou DCIR. Ainsi, le blocage de BDCA-2 et de DCIR avec des fragments Fab des anticorps monoclonaux préserve la capacité des pDCs à produire des IFNs de type I et III en présence des particules virales.Plasmacytoid dendritic cells (pDCs) respond to viral infection by production of alpha interferon (IFN-alpha), proinflammatory cytokines, and cell differentiation. The elimination of hepatitis C virus (HCV) in more than 50% of infected patients by treatment with IFN-alpha suggests that pDCs play an important role in the control of HCV infection. pDCs exposed to HCV infected hepatoma cells produce large amounts of IFN-alpha. However, despite large amounts of Toll-like receptor 7-mediated IFN-α, produced by pDCs, HCV still replicates in infected liver. During my PhD training, I went into in depth to understand the molecular mecanisms used by HCV particles and HCV infected hepatocytes to explore pDCs. I focused my research on the binding of HCV particles with the pDC surface, on the triggered downstream signaling pathway, on the cellular differentiation. Our results suggest that cell-associated HCV signals in pDCs via an endocytosis-dependent mechanism and IRF7 but not via the NF-kappaB pathway. In spite of IFN-alpha induction, cell-associated HCV does not induce a full functional response of pDCs. HCV particles inhibit, via binding of E2 glycoprotein to CLRs, production of IFN-α and IFN-λ in pDCs exposed to HCV-infected hepatocytes, and induce in pDCs a rapid phosphorylation of Akt and Erk1/2, in a manner similar to the crosslinking of BDCA-2 or DCIR. Blocking of BDCA-2 and DCIR with Fab fragments of monoclonal antibodies preserves the capacity of pDCs to produce type I and III IFNs in the presence of HCV particles

Towards hybrid socio-technical solutions for urban water and energy provision

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