Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an \emph{in vitro} model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a "self-generated" gradient mechanisms that accelerates the extension of the sprout.Comment: 48 pages, 10 figures, 8 supplementary figures. Accepted for publication in PLoS ON

Predictors of Walking App Users With Comparison of Current Users, Previous Users, and Informed Nonusers in a Sample of Dutch Adults: Questionnaire Study

BACKGROUND: The last decade has seen a substantial increase in the use of mobile health apps and research into the effects of those apps on health and health behaviors. In parallel, research has aimed at identifying population subgroups that are more likely to use those health apps. Current evidence is limited by two issues. First, research has focused on broad health apps, and little is known about app usage for a specific health behavior. Second, research has focused on comparing current users and current nonusers, without considering subgroups of nonusers. OBJECTIVE: We aimed to provide profile distributions of current users, previous users, and informed nonusers, and to identify predictor variables relevant for profile classification. METHODS: Data were available from 1683 people who participated in a Dutch walking event in Amsterdam that was held in September 2017. They provided information on demographics, self-reported walking behavior, and walking app usage, as well as items from User Acceptance of Information Technology, in an online survey. Data were analyzed using discriminant function analysis and multinomial logistic regression analysis. RESULTS: Most participants were current walking app users (899/1683, 53.4%), while fewer participants were informed nonusers (663/1683, 39.4%) and very few were previous walking app users (121/1683, 7.2%). Current walking app users were more likely to report walking at least 5 days per week and for at least 30 minutes per bout (odds ratio [OR] 1.44, 95% CI 1.11-1.85; P=.005) and more likely to be overweight (OR 1.72, 95% CI 1.24-2.37; P=.001) or obese (OR 1.49, 95% CI 1.08-2.08; P=.005) as compared with informed nonusers. Further, current walking app users perceived their walking apps to be less boring, easy to use and retrieve information, and more helpful to achieve their goals. Effect sizes ranged from 0.10 (95% CI 0.08-0.30) to 1.58 (95% CI 1.47-1.70). CONCLUSIONS: The distributions for walking app usage appeared different from the distributions for more general health app usage. Further, the inclusion of two specific subgroups of nonusers (previous users and informed nonusers) provides important information for health practitioners and app developers to stimulate continued walking app usage, including making information in those apps easy to understand and making it easy to obtain information from the apps, as well as preventing apps from becoming boring and difficult to use for goal attainment

Injury prevention in team sport athletes:The role of screening tools and injury prevention programs

In balsporten zoals voetbal en basketbal komen veel blessures voor, vooral aan de benen. Gezien de fysieke en psychologische gevolgen van deze blessures voor sporters en de hoge kosten die hiermee gepaard gaan, is preventie van groot belang. Coa¬ches en atleten zijn echter vaak terughoudend met de implementatie van blessurepreventie programma’s. Het doel van dit proefschrift is om meer kennis te verkrijgen over blessure screeningtools en preventie programma’s voor beenblessures. Eerst wordt een overzicht gegeven van bestaande blessure screeningtesten en bevorderende of belemmerende factoren voor de implementatie van deze testen in de praktijk. Voorbeelden van gevonden blessure screeningtesten zijn flexibiliteit-, kracht- en balanstesten. Vervolgens ligt de focus op preventieprogramma’s voor voorste kruisbandblessures. Instructies in deze blessurepreventie programma’s kunnen intern (IF) ‘buig je knieën’ of extern (EF) ‘probeer zacht te landen’ gefocust zijn. EF-instructies kunnen automatische leerprocessen stimuleren, de sporter focust op het doel van de beweging in plaats van op de beweging zelf. Dallinga introduceert nieuwe methodes om bestaande blessurepreventie programma’s te optimaliseren, gebruik makende van EF-instructies en videofeedback. Na evaluatie vond zij dat mannelijke spelers hun bewegingspatroon verbeterden na videofeedback. Dallinga concludeert dat er verscheidene blessurescreening tools zijn om blessures te voorspellen. Met als kanttekening dat de voorspellende kracht, de toepasbaarheid en de sportspecificiteit nog verder onderzocht moeten worden. Visuele feedback lijkt daarnaast een veelbelovende manier om mannelijke teamsporters een landingspatroon aan te leren. Voor vrouwen geldt het advies om naast videofeedback verbale EF-instructies aan te bieden. In toekomstig onderzoek dienen de geïntroduceerde methodes in een echte sportsetting getest te worden

Rat apolipoprotein A-IV metabolism

Earlier studies by Van 't Hoeft et al. (85, 160), in our laboratory, mainly focussed upon the catabolism of HDL apolipoproteins A-I and E. They found that the kidneys were an important organ involved in the catabolism of these proteins together with the liver. The present thesis mainly deals with HDL apo A-IV. Until very recently, apo A-IV metabolism was relatively unknown. This was due to the fact that, during isolation of HDL particles by density ultracentrifugation, apo A-IV was readily "stripped" and recovered in the "bottom" fraction, together with the bulk of the serum protein. Better isolation procedures enabled us to investigate the behaviour of apo A-IV in the rat, leading to expansion of our knowledge of lipoprotein metabolism in general. The first part (Chapter 2) outlines a sensitive electroimmunoassay for the determination of apo A-I, apo E, and apo A-IV in diluted samples. This method has been successfully used to analyse the distribution of these proteins in rat mesenteric lymph (Chapter 3) and rat serum (Chapter 4), following their fractionation by molecular sieve chromatography on agarose gels. The latter procedure was employed to obviate the well known problem of particle protein stripping which occurs during ultracentrifugation (60, 86-88). Chapter 4 describes the results of a study designed to compare the effects of gel filtration and ul tracentrifugation on HDL particle composition. Chapters 5 and 6 describe our studies on the catabolic sites of apolipoprotein A-IV containing lipoproteins. The final paper (Chapter 7) describes the analysis of HDL subclasses using specific immunoprecipitation

Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice

F.B. is supported by Swedish Research Council, Swedish Diabetes Foundation, Swedish Heart Lung Foundation, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg foundation, Göran Gustafsson Foundation, Ingbritt and Arne Lundberg’s foundation, Swedish Heart Lung Foundation, Torsten Söderberg’s Foundation, Ragnar Söderberg’s Foundation, NovoNordisk Foundation, AFA insurances, and LUA-ALF grants from Västra Götalandsregionen and Stockholm County Council. F.B. is a recipient of ERC Consolidator Grant (European Research Council, Consolidator grant 615362—METABASE). W.M.d.V. is supported by the Finland Academy of Sciences (grants 137389, 141140 and 1272870 ), the Netherlands Organization for Scientific Research (Spinoza Award and SIAM Gravity Grant 024.002.002) and the European Research Council (ERC Advanced Grant 250172 MicrobesInside). M.N. is supported by a ZONMW-VIDI grant 2013 (016.146.327).Peer reviewedPublisher PD