The antigenic evolution of fast-evolving viruses

During antigenic evolution, a virus alters its presentation to the immune system, reducing the ability of the immune system to recognize and protect against the virus. Those viruses that most successfully escape from immune protection are selected for in the evolutionary process. These viruses are most likely to predominate in the future viral population. The selection pressures that shape this evolution are computable from models that use molecular input data on the interaction between the virus and the immune system. Given these selection pressures, future evolutionary trajectories of viruses can be predicted. These predictions help the timely identification of emerging variants and inform the most protective antigenic composition of vaccinations. Alternatively, given frequency trajectories of viral evolution, key parameters can be learned that describe the molecular interaction between the virus and the immune system. These parameters describe the effects of immune therapy while considering the evolutionary response of the virus explicitly. In this thesis, I discuss the antigenic evolution of three fast-evolving viruses. First, I analyze the in vivo antigenic escape evolution of HIV-1 from a broadly neutralizing antibody. In this analysis, I use data from clinical trials to infer key fitness parameters that determine escape evolution across multiple hosts. Second, I present an antigenic model to predict the evolutionary trajectories of SARS-CoV-2. The model is the first to use human antigenic data to predict viral evolution. In this work, I combine genetic, epidemiological, and antigenic data to model the population immunity that determines viral fitness. The fitness model can predict the short-term evolution of SARS-CoV-2, as well as predict the antigenic profile of future escape variants. Finally, I present a set of methods for the evolutionary analysis of influenza. It contains methods on evolutionary tracking, inference of selection, inference and tracking of population immunity, fitness modelling, and computation of vaccine protection. The focus is on influenza, but the methods are also relevant to other respiratory viruses, in particular SARS-CoV-2. Together, the work shows how the selection pressures that steer the antigenic evolution of viruses can be computed. Antigenic evolution is predictable. Fitness modelling of antigenic evolution can aid the design of better immune therapies against HIV-1 and improve the antigenic composition of vaccinations that protect people against respiratory viruses

Reconstructing Neogene surface uplift of the Alps: Integrating stable isotope paleoaltimetry and paleoclimate modelling

Paleoaltimetry - the reconstruction of the elevation of mountain ranges in the geological past - is key to understanding the geodynamic drivers of surface uplift. Simultaneously, surface uplift of Earth’s major mountain ranges redirected atmospheric flow and impacted climate globally. At a smaller scale, mountain building affects regional climate and biodiversity. Stable isotope paleoaltimetry is a powerful tool to quantify the past elevation of mountain ranges. It is based on the inverse relationship between the stable isotopic composition of meteoric waters and elevation, which is represented by the so-called isotopic lapse rate. However, variations in climatic parameters modify isotopic lapse rates and impact moisture transport over the continents and consequently affect paleoelevation reconstructions. Here, we show the results of a combined stable isotope paleoaltimetry and paleoclimate modeling approach in the European Alps. This approach allows for an improved and more realistic estimation of isotopic lapse rates, large-scale isotope-in-precipitation patterns over Europe and hence Alpine paleoaltimetry calculations. The European Alps are an ideal target for a combined paleoaltimetry - climate modeling approach, given that they are (a) one of the most-studied mountain ranges for which many geoscientific data are available, and (b) sufficiently small and oriented near-parallel to dominant atmospheric circulation patterns. The latter implies that no major global climatic changes are expected in response to Alpine surface uplift, as opposed to e.g. the Andes or the Tibet-Himalaya mountain ranges. Results from 4D-MB SPP phase 1 and 2 show that: (1) Changing the surface elevation of even a small orogen can complicate stable isotope paleoaltimetry by mixing the elevation and climate signal in a more complex way than commonly assumed. Climate models can help separate these signals and constrain surface uplift histories. (2) The Central Alps were already high during the Early and Middle Miocene, whereas the Eastern Alps were still at significantly lower elevations, thereby confirming that surface uplift propagated from west to east, as would be expected from oblique continent-continent collision. Together, the results highlight the importance and viability of this combined, interdisciplinary approach. Based on the results from 4D-MB SPP phase 1 and 2, we propose that future efforts to reconstruct surface uplift of mountain ranges follow this state-of-the-art approach, while keeping local limitations to proxy material availability and access to facilities in mind

Bacteriological quality and intake of acidified drinking water in Wistar rats is pH-dependent

The effects of acidification of drinking water on bacteriological quality and water intake in adult, male Wistar rats. was studied in 2 consecutive experiments. HCl was used to aeidify water to pH 2.5, 3.0 and 3.5. Control groups received untreatedtap or demineralized water. Acidification of water with HCl to pH 2.5 effectively prevented growth of aerobic bacteria in the drinking water bottles after a number of days, but also caused a reproducible decline in water intake when compared to untreated water. A reduced water intake may indicate disturbed wellbeing and may interfere with experimental results. Acidification to pH 3.0 also kept bacteriological counts low and did not reduce water intake when compared to rats drinkingnon-acidified water. Acidification to pH 3.5 led to high bacteriological counts after a few days. On the basis of these 2 experiments, acidification of drinking water with 1101 to pH 3.0 is advised

Brutus versus Caesar

Vijfentwintig jaar geleden sneuvelde het kabinet-Cals na een lange nachtelijke strijd in de Tweede kamer. Het kabinet had zich in een ongelukkige positie gemanoeuvreerd door uitdrukkelijk om een vertrouwensvotum te vragen. De kritische motie-Schmelzer werd daarop fataal. Sindsdien is de "Nacht van Schmelzer" velen blijven intrigeren. Recentelijk laaide de discussie opnieuw op