Small-scale piped water supply: end-user inclusive water research in arsenic affected areas in India and Bangladesh (DELTAP)

DELTAP is s multi-disciplinary research project, where geologists, water treatment scientists and industrial design engineers join forces to develop an integrated approach towards small-scale piped water supply (SPWS) systems in the arsenic-affected Ganges-Brahmaputra-Meghna Delta. The project has started in 2016 with a field study in Bihar (India) with a focus on water quality mapping with mobile crowd participation. The coming years the research will continue with 3 PhD candidates, both in India and Bangladesh, with the ultimate aim to develop blueprints for end-user inclusive SPWS systems

Response Functions to Critical Shocks in Social Sciences: An Empirical and Numerical Study

We show that, provided one focuses on properly selected episodes, one can apply to the social sciences the same observational strategy that has proved successful in natural sciences such as astrophysics or geodynamics. For instance, in order to probe the cohesion of a policy, one can, in different countries, study the reactions to some huge and sudden exogenous shocks, which we call Dirac shocks. This approach naturally leads to the notion of structural (as opposed or complementary to temporal) forecast. Although structural predictions are by far the most common way to test theories in the natural sciences, they have been much less used in the social sciences. The Dirac shock approach opens the way to testing structural predictions in the social sciences. The examples reported here suggest that critical events are able to reveal pre-existing ``cracks'' because they probe the social cohesion which is an indicator and predictor of future evolution of the system, and in some cases foreshadows a bifurcation. We complement our empirical work with numerical simulations of the response function (``damage spreading'') to Dirac shocks in the Sznajd model of consensus build-up. We quantify the slow relaxation of the difference between perturbed and unperturbed systems, the conditions under which the consensus is modified by the shock and the large variability from one realization to another

Characterizing and TRAPing a Social Stress-Activated Neuronal Ensemble in the Ventral Tegmental Area

Social stress is a major contributor to neuropsychiatric issues such as depression, substance abuse and eating disorders. The ventral tegmental area (VTA) is involved in the effects of stress on cognitive and emotional processes perturbed in these disorders. However, the VTA is a cellularly heterogeneous brain area and it remains unclear which of its neuronal populations make up the social stress-sensitive ensemble. The current study characterizes the molecular, topographical and functional properties of VTA social stress-activated cells. First, we used immunohistochemical analysis of Fos protein, a marker of recent increased neuronal activity, to show that acute social stress activates a mainly neuronal ensemble in the VTA (VTA Social stress neurons). Topographical analysis showed that this ensemble, which comprises ∼11% of all VTA neurons, occurs across VTA subregions. Further analysis showed that approximately half of the VTA Social stress neurons express the dopamine synthesis rate-limiting enzyme tyrosine hydroxylase (TH). In a minority of cases this occurred with coexpression of vesicular glutamate transporter 2 (Vglut2). Also part of the ensemble were VTA cells expressing just Vglut2 without TH, and cells expressing the vesicular GABA transporter (VGAT) without TH. Next, using targeted recombination in active populations (TRAP2), we showed that VTA Social stress neurons can be permanently tagged and made tractable for future functional investigations. Using a combination of TRAP2 and patch-clamp electrophysiology we demonstrate that VTA Social stress neurons exhibit higher excitability than their non-TRAPed neighbor cells. Overall, this study shows that acute social stress activates an ensemble of neurons throughout the VTA, comprising distinct molecular identities, and with specific electrophysiological features. It also identifies TRAP2 as a tool to make this ensemble tractable for future functional studies

Ethnocentrism in the Low Countries: A comparative perspective

Contains fulltext : 3361.pdf (publisher's version ) (Open Access)New Community, continued by: Journal of ethnic and migration studies [1369-183X

Evaluation of spelt germplasm for polyphenol oxidase activity and aluminium resistance

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time

Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C

There is a great need for antiviral drugs to treat enterovirus (EV) and rhinovirus (RV) infections, which can be severe and occasionally life-threatening. The conserved nonstructural protein 2C, which is an AAA+ ATPase, is a promising target for drug development. Here, we present a structure-activity relationship study of a previously identified compound that targets the 2C protein of EV-A71 and several EV-B species members, but not poliovirus (PV) (EV-C species). This compound is structurally related to the Food and Drug Administration (FDA)-approved drug fluoxetine—which also targets 2C—but has favorable chemical properties. We identified several compounds with increased antiviral potency and broadened activity. Four compounds showed broad-spectrum EV and RV activity and inhibited contemporary strains of emerging EVs of public health concern, including EV-A71, coxsackievirus (CV)-A24v, and EV-D68. Importantly, unlike (S)-fluoxetine, these compounds are no longer neuroactive. By raising resistant EV-A71, CV-B3, and EV-D68 variants against one of these inhibitors, we identified novel 2C resistance mutations. Reverse engineering of these mutations revealed a conserved mechanism of resistance development. Resistant viruses first acquired a mutation in, or adjacent to, the α2 helix of 2C. This mutation disrupted compound binding and provided drug resistance, but this was at the cost of viral fitness. Additional mutations at distantly localized 2C residues were then acquired to increase resistance and/or to compensate for the loss of fitness. Using computational methods to identify solvent accessible tunnels near the α2 helix in the EV-A71 and PV 2C crystal structures, a conserved binding pocket of the inhibitors is proposed

Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food

Stress can cause overconsumption of palatable high caloric food. Despite the important role of stress eating in obesity and (binge) eating disorders, its underlying neural mechanisms remain unclear. Here we demonstrate in mice that stress alters lateral hypothalamic area (LHA) control over the ventral tegmental area (VTA), thereby promoting overconsumption of palatable food. Specifically, we show that glutamatergic LHA neurons projecting to the VTA are activated by social stress, after which their synapses onto dopamine neurons are potentiated via AMPA receptor subunit alterations. We find that stress-driven strengthening of these specific synapses increases LHA control over dopamine output in key target areas like the prefrontal cortex. Finally, we demonstrate that while inducing LHA-VTA glutamatergic potentiation increases palatable fat intake, reducing stress-driven potentiation of this connection prevents such stress eating. Overall, this study provides insights in the neural circuit adaptations caused by stress that drive overconsumption of palatable food

Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells