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The City as Black Box: Navigating Through the Surplus of Information

Prednisolone induces the Wnt signalling pathway in 3T3-L1 adipocytes

Synthetic glucocorticoids are potent anti-inflammatory drugs but show dose-dependent metabolic side effects such as the development of insulin resistance and obesity. The precise mechanisms involved in these glucocorticoid-induced side effects, and especially the participation of adipose tissue in this are not completely understood. We used a combination of transcriptomics, antibody arrays and bioinformatics approaches to characterize prednisolone-induced alterations in gene expression and adipokine secretion, which could underlie metabolic dysfunction in 3T3-L1 adipocytes. Several pathways, including cytokine signalling, Akt signalling, and Wnt signalling were found to be regulated at multiple levels, showing that these processes are targeted by prednisolone. These results suggest that mechanisms by which prednisolone induce insulin resistance include dysregulation of wnt signalling and immune response processes. These pathways may provide interesting targets for the development of improved glucocorticoids.

Muscle volume is a critical determinant of rowing performance in Olympic rowers

Molecular insights into human taste perception and umami tastants: A review

Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.

Over uitdagingen, kansen en wensen in de transitie naar levende teeltsystemen.

Door een opeenstapeling van maatschappelijke, ecologische en politieke crisissen nemen de wensen en eisen die aan de tuinbouwsector gesteld worden hand over hand toe. Aan de andere kant nemen ook de kansen en mogelijkheden door toegenomen kennis en voortdenderende technologische ontwikkelingen rap toe. De tuinbouw verkeert hierdoor in dermate wild vaarwater dat, gezien de veelvoud aan transities, gerust gesproken kan worden van een systeemtransitie. Een systeemtransitie naar een ecologisch en economisch duurzame tuinbouw door productiesystemen die zowel stabiel als hoogproductief zijn, vraagt niet om een vlucht in het verleden, maar om een sprong de toekomst in. Een sprong naar een productiesysteem gebaseerd op kennis van de plant en de interactie met zijn (ecologische) omgeving, ondersteund door hoogwaardige technologie met een hernieuwde vorm van procescontrole. In dit essay onderzoek ik hoe ik als associate lector levende teeltsystemen voor Inholland bij wil dragen aan onderzoek en onderwijs op de actuele transitiepaden van de glastuinbouw. Hoe ik kan bijdragen aan kennis ontwikkeling, nieuwe methoden ontwerpen in onderzoek en deze vertalen naar praktijkgerichte oplossingen. Zo wil ik door samenwerking met collega-onderzoekers en studenten van binnen en buiten Inholland verder invulling geven aan de realisatie van mijn missie. “In onderzoek en onderwijs bijdragen aan een tuinbouwproductiesysteem dat functioneert als een ecosysteem, waarin het samenspel van een grote diversiteit aan levende organismen bijdraagt aan de gezondheid van het productiesysteem en het product dat het produceert. Waarin onze gezamenlijke kennis tot de kunde leidt om levende teeltsystemen als evenwichtige ecosystemen te ontwerpen en te beheren. Waarin telers de biodiversiteit versterken en verzorgen, zodat deze bijdraagt aan de kwaliteitsproductie, in een samenspel van technologie, ecologie en menselijk vernuft. Tuinbouw dus die de wereld van gezonde producten voorziet en in balans is met zichzelf en haar omgeving.”

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells.RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNγ, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCθ are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCθ in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCθ dependent IFNγ production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells.CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCθ dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood.