Imaging Von Willebrand Factor during storage and upon secretion by light and electron microscopy

Blood coagulation is vital for life by reducing blood loss upon injury. One of the key players in the initial steps of coagulation is Von Willebrand Factor (VWF). VWF is mainly produced and stored by the cells that line the blood vessels and functions upon secretion by creating a platelet plug at the side of injury. Mutations in VWF can disturb this process, for instance through insufficient VWF secretion, which causes Von Willebrand disease, a hereditary bleeding disorder characterized by prolonged bleeding. As the morphology of VWF is highly related to its functionality, we aimed to obtain more knowledge on the mechanisms that can be affected in Von Willebrand disease by studying the normal lifecycle of VWF using correlative light and electron microscopy (CLEM). CLEM combines fluorescent light microscopy with electron microscopy on the same sample to obtain structural information of specific biological events that are difficult to study with electron microscopy alone. Using CLEM, novel information was obtained regarding the formation of the VWF storage organelle, in addition we also discovered novel pathophysiological mechanisms acting during VWF secretion that may be effectuated in Von Willebrand disease.NWO grant 91209006UBL - phd migration 201

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Precipitatie in aluminium-metaal matrix composieten

Chemical EngineeringApplied Science

A comparitive study on heat effects in an Al-Cu alloy reinforced with silicon particles and in a binary Al-Cu alloy

PreprintChemical EngineeringApplied Science

Études calorimétriques différientielles de la précipitation dans quelques alliages d'aluminium

Chemical EngineeringApplied Science

Cooling and heating rate dependence of precipitation in an Al-Cu alloy

Differential scanning calorimetry and X-ray diffraction were used to study the cooling and heating rate dependence of precipitation in an Al-1.66 at.% Cu alloy. After homogenizing, cooling at a rate of 22 K min?1 (SC22) is sufficient to retain all copper in solid solution. GP-zone formation during subsequent heat treatment is hindered; this is ascribed to an insufficient number of (excess) vacancies. After a water quench (WQ) a large number of GP zones are formed during subsequent storage at room temperature for 1 h. The heat content of the GP-zone dissolution effect can quantitatively be described in terms of the heat of precipitation of GP I zones and the solid solubilities as derived from the GP I zone solvus. The heat content of the combined ??-/?-phase precipitation effect appeared to be proportional to the number of copper atoms precipitated, yielding an average value for the heat of copper precipitation of 36 kJ mol?1 copper. The activation energy for ??-phase formation is 0.75 eV for SC22 specimens and 1.10 ± 0.10 eV for WQ specimens. The differences in reported activation energies for ??-phase formation are discussed in terms of mobility of dissolve atoms (related to the vacancy concentration), interfacial energy and direction of growth (normal or perpendicular to the ??-phase plate)