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Biology subjects

Mul, E.

Publications and source records attributed to Mul, E..

3 recordsLinked to original sources

AN IMAGING FLOW CYTOMETRY-BASED METHODOLOGY FOR THE ANALYSIS OF SINGLE EXTRACELLULAR VESICLES IN UNPROCESSED HUMAN PLASMA

Extracellular vesicles (EVs) are tissue-specific particles released by cells containing valuable diagnostic information in the form of various biomolecules. To rule out selection bias or introduction of artefacts caused by EV isolation techniques, we present a clinically feasible, imaging flow cytometry (IFCM)-based methodology to phenotype and determine the concentration of EVs with a diameter [≤]400 nm in human platelet-poor plasma (PPP) without prior isolation of EVs. Instrument calibration (both size and fluorescence) were performed with commercial polystyrene beads. Detergent treatment of EVs was performed to discriminate true vesicular events from artefacts. Using a combination of markers (CFSE & Tetraspanins, or CD9 & CD31) we found that >90% of double-positive fluorescent events represented single EVs. Through this work, we provide a framework that will allow the application of IFCM for EV analysis in peripheral blood plasma in a plethora of experimental and potentially diagnostic settings. Additionally, this direct approach for EV analysis will enable researchers to explore new corners of EV as cellular messengers in healthy and pathological conditions.

cell biology↗

Epigenomic and functional dynamics of human bone marrow myeloid differentiation to mature blood neutrophils

Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic and functional overview of their differentiation stages from bone marrow-residing progenitors to mature circulating cells. Integration of epigenetic and transcriptome dynamics reveals an enforced regulation of differentiation, through cellular functions such as: release of proteases, respiratory burst, cell cycle regulation and apoptosis. We observe an early establishment of the cytotoxic capability, whilst the signaling components that activate antimicrobial mechanisms are transcribed at later stages, outside the bone marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these data reveal how the developmental dynamics of the epigenetic landscape orchestrate the daily production of large number of neutrophils required for innate host defense and provide a comprehensive overview of the epigenomes of differentiating human neutrophils.\n\nKey pointsO_LIDynamic acetylation enforces human neutrophil progenitor differentiation.\nC_LI\n\nO_LINeutrophils cytotoxic capability is established early at the (pro)myelocyte stage.\nC_LI\n\nO_LICoordinated signaling component expression prevents unwanted toxic effects to the bone marrow niche.\nC_LI

immunology↗

Harbour seals are regaining top-down control in a coastal ecosystem

Historic hunting has led to severe reductions of many marine mammal species across the globe. After hunting ceased, some populations have recovered to pre-exploitation levels, and may again act as a top-down regulatory force on marine ecosystems. Also the harbour seal population in the international Wadden Sea grew at an exponential rate following a ban on seal hunting in 1960s, and the current number [~]38,000 is close to the historic population size. Here we estimate the impact of the harbour seal predation on the fish community in the Wadden Sea and nearby coastal waters.\n\nFish remains in faecal samples and published estimates on the seals daily energy requirement were used to estimate prey selection and the magnitude of seal consumption. Estimates on prey abundance were derived from demersal fish surveys, and fish growth was estimated using a Dynamic Energy Budget model. GPS tracking provided information on where seals most likely caught their prey.\n\nHarbour seals from the Dutch Wadden Sea fed predominantly on demersal fish, e.g. flatfish species (flounder, sole, plaice, dab), but also sandeel, cod and whiting. Total fish biomass in the Wadden Sea was insufficient to sustain the estimated prey consumption of the entire seal population year-round. This probably explains why seals also acquire prey further offshore in the adjacent North Sea, only spending 13% of their diving time in the Wadden Sea. Still, seal predation was estimated to cause an average annual mortality of 43% and 60% on fish in the Wadden Sea and adjacent coastal zone, respectively. There were however large sources of uncertainty in the estimate, including the migration of fish between the North Sea and Wadden Sea, and catchability estimates of the fish survey sampling gear, particularly for sandeel and other pelagic fish species.\n\nOur estimate suggested a considerable top-down control by harbour seals on demersal fish. However predation by seals may also alleviate density-dependent competition between the remaining fish, increasing fish growth, and partly compensating for the reduction in fish numbers. This study shows that recovering coastal marine mammal populations could potentially become an important component in the functioning of shallow coastal systems.

ecology↗