Klimaat onderzoek bij het Nederlands Instituut voor Onderzoek der Zee

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Clinically applicable CD34(+)-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses

Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34(+) hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141(+)CLEG9A(+) cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-alpha. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Right-wing radical populism in city and suburbs: an electoral geography of the Partij Voor de Vrijheid in the Netherlands

This paper looks at the electoral geography of the Partij Voor de Vrijheid, a Dutch right-wing radical populist party, which is anti-immigration, anti-establishment and critical of urban conditions. Combining survey analyses and geocoded polling station data analyses of the 2010 parliamentary elections, it is found that overrepresentation of support in suburban environments cannot be explained by voter composition alone. There is a positive contextual effect in lower-density neighbourhoods in cities and in suburban municipalities, as well as in post-war New Towns. To account for spatial variations, an explanatory framework is proposed based on urban theories of class, revanchism and nostalgia. Traditional middle classes, concentrated in suburbs, seem to support RRPPs to reclaim urban space for daily use and as a defensive strategy in view of metropolitan change

Marine production in the Congo-influenced SE Atlantic over the past 30,000 years: A novel dinoflagellate-cyst based transfer function approach

The sediments from the Congo deep-sea fan contain valuable information about past environmental conditions of the east equatorial Atlantic during the transition from the Last Glacial Maximum (LGM) to present-day climatic conditions. The high-resolution marine (organic-walled dinoflagellate cysts = dinocysts) and terrestrial (pollen) palynological records from two cores off equatorial West Africa, covering the last 30,000 years, document three major phases in surface productivity. (1) During the LGM relative sea level was low, nutrient enrichment due to seasonal coastal upwelling prevailed off the Congo mouth and high aridity prevailed in the catchment area. (2) At around 15.2 cal ka BP, monsoonal precipitation strengthened over the Congo Basin, generating high river discharges, river-induced upwelling, and increased nutrient flux to the ocean. In parallel, erosion of shelf sediments during shelf transgression further enhanced nutrient flux. (3) At around 9-8 cal ka BP, rainforest vegetation inhibited soil erosion, depleted nutrient supply, and restricted marine productivity to its modern levels. The study presents the application of modern analogues and a dinocyst transfer function to the reconstruction of primary palaeoproductivity (PP) in a region of freshwater influence. A database of recent dinocyst assemblages comprising of 208 sites in the equatorial Atlantic enabled the reconstruction of sea-surface annual PP 1.3 times higher during the LGM and also during the deglaciation, between 15.2 and 13.2 cal ka BP. The reconstruction is independent of, and thus provides corroboration for, other biological and geochemical proxies. © 2008 Elsevier B.V. All rights reserved

Bifunctional protein PCBD2 operates as a co-factor for hepatocyte nuclear factor 1β and modulates gene transcription.

Contains fulltext : 232382.pdf (Publisher’s version ) (Open Access)Hepatocyte nuclear factor 1β (HNF1β) is an essential transcription factor in development of the kidney, liver, and pancreas. HNF1β-mediated transcription of target genes is dependent on the cell type and the development stage. Nevertheless, the regulation of HNF1β function by enhancers and co-factors that allow this cell-specific transcription is largely unknown. To map the HNF1β interactome we performed mass spectrometry in a mouse kidney inner medullary collecting duct cell line. Pterin-4a-carbinolamine dehydratase 2 (PCBD2) was identified as a novel interaction partner of HNF1β. PCBD2 and its close homolog PCBD1 shuttle between the cytoplasm and nucleus to exert their enzymatic and transcriptional activities. Although both PCBD proteins share high sequence identity (48% and 88% in HNF1 recognition helix), their tissue expression patterns are unique. PCBD1 is most abundant in kidney and liver while PCBD2 is also abundant in lung, spleen, and adipose tissue. Using immunolocalization studies and biochemical analysis we show that in presence of HNF1β the nuclear localization of PCBD1 and PCBD2 increases significantly. Promoter luciferase assays demonstrate that co-factors PCBD1 and PCBD2 differentially regulate the ability of HNF1β to activate the promoters of transcriptional targets important in renal electrolyte homeostasis. Deleting the N-terminal sequence of PCBD2, not found in PCBD1, diminished the differential effects of the co-factors on HNF1β activity. All together these results indicate that PCBD1 and PCBD2 can exert different effects on HNF1β-mediated transcription. Future studies should confirm whether these unique co-factor activities also apply to HNF1β-target genes involved in additional processes besides ion transport in the kidney.01 april 202