Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice

Background: Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings: Focal cerebral ischemia was induced in Vasp2/2 mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan’s Blue tracer was applied to visualize the extent of blood-brainbarrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p,0.05) and edema volumes (1.7 mm360.5 mm3 versus 0.8 mm360.4 mm3; p,0.0001) were significantly enhanced in Vasp2/2 mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3617.3 mm3 versus 39.3 mm3610.7 mm3, respectively; p,0.01) and a non significant trend (p.0.05) towards worse neurological outcomes. Conclusion: Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumour agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible. The Pharmacology and Molecular Mechanisms (PAMM) group of the European Organization for Research and Treatment of Cancer (EORTC) is the largest group of academic scientists working on drug development and bundle decades of expertise in this field. This position paper addresses all researchers with an interest in the preclinical and cellular pharmacology of anti-tumour agents and aims at generating basic recommendations for the correct use of compounds to be tested for anti-tumour activity using a range of preclinical cellular models of cancer

Equilibrium melting temperature and crystallization kinetics of α- and β′-PBN crystal forms

The melting behavior and crystallization kinetics of PBN–PDEN and PBN–PTDEN copolymers were investigated using differential scanning calorimetry. Multiple endotherms were observed in all of the copolymers under investigation, originating from melting and recrystallization processes. By applying the Hoffman–Weeks method, the Tm1 of the a and b¢-PBN phases were derived. The Tm1 value of the b¢-form, which has not been determined before, is significantly higher, as expected, because the b¢-phase is thermodynamically favored and more tightly packed. The isothermal crystallization kinetics were analyzed according to the Avrami treatment. The presence of either oxygen or sulfur atoms in the PBN polymeric chain was found to reduce its crystallizability. In particular, the crystallization rate regularly decreased as the co-unit content was increased. Lastly, the a-PBN phase was found to crystallize faster than b¢-one, which is expected, as it the more kinetically favored phase

Haptonomic guidance of pregnancy and the prenatal attachment of both parents to their unborn child

In een quasi-experimenteel design met een voor- en nameting en een interventie- (n = 46) en een controlegroep (n = 38) is onderzocht of haptonomische zwangerschapsbegeleiding (HZB) meerwaarde heeft voor het bevorderen van prenatale gehechtheid ten opzichte van andere vormen van of geen zwangerschapsbegeleiding. Methode Vragenlijsten (MAAS/PAAS, MFAS) en een beeldrepresentatie betreffende de gevoelsmatige afstand tussen ouder en ongeboren kind (PRAM) werden ingevuld op 20 en 35 weken zwangerschap. Resultaten De resultaten lieten in beide groepen een nagenoeg gelijke toename van de prenatale gehechtheid zien. Conclusie Prenatale gehechtheid neemt toe ongeacht óf men begeleiding krijgt en zo ja, welke. Aanvullend onderzoek of HZB prenatale gehechtheid kan bevorderen bij moeders met een risico op verminderde prenatale gehechtheid lijkt gerechtvaardigd op basis van de theoretisch goed onderbouwde werkzame elementen van de begeleiding

Freshwater phytoplankton diversity: models, drivers and implications for ecosystem properties

Our understanding on phytoplankton diversity has largely been progressing since the publication of Hutchinson on the paradox of the plankton. In this paper, we summarise some major steps in phytoplankton ecology in the context of mechanisms underlying phytoplankton diversity. Here, we provide a framework for phytoplankton community assembly and an overview of measures on taxonomic and functional diversity. We show how ecological theories on species competition together with modelling approaches and laboratory experiments helped understand species coexistence and maintenance of diversity in phytoplankton. The non-equilibrium nature of phytoplankton and the role of disturbances in shaping diversity are also discussed. Furthermore, we discuss the role of water body size, productivity of habitats and temperature on phytoplankton species richness, and how diversity may affect the functioning of lake ecosystems. At last, we give an insight into molecular tools that have emerged in the last decades and argue how it has broadened our perspective on microbial diversity. Besides historical backgrounds, some critical comments have also been mad