Nonlinear Finite Element Analysis of Nanoindentation of Viral Capsids

Recent Atomic Force Microscope (AFM) nanoindentation experiments measuring mechanical response of the protein shells of viruses have provided a quantitative description of their strength and elasticity. To better understand and interpret these measurements, and to elucidate the underlying mechanisms, this paper adopts a course-grained modeling approach within the framework of three-dimensional nonlinear continuum elasticity. Homogeneous, isotropic, elastic, thick shell models are proposed for two capsids: the spherical Cowpea Chlorotic Mottle Virus (CCMV), and the ellipsocylindrical bacteriophage $\phi 29$. As analyzed by the finite element method, these models enable parametric characterization of the effects of AFM tip geometry, capsid dimensions, and capsid constitutive descriptions. The generally nonlinear force response of capsids to indentation is shown to be insensitive to constitutive details, and greatly influenced by geometry. Nonlinear stiffening and softening of the force response is dependent on the AFM tip dimensions and shell thickness. Fits of the models capture the roughly linear behavior observed in experimental measurements and result in estimates of Young's moduli of $\approx$280--360 MPa for CCMV and $\approx$4.5 GPa for $\phi 29$.Comment: 24 pages, 10 figures, submitted to Biophysical Journa

Carbon and nitrogen cycling in the Scheldt estuary: the major players, long-term changes and an integrated view

The Scheldt estuary is a highly heterotrophic, nutrient-rich, turbid, tidal estuary in a densely populated area (Belgium/The Netherlands). Here we present the results (1) on the long-term changes in nutrient loadings and transformations within the estuary and (2) on nitrogen cycling rate measurements obtained with isotopic tracers. Moreover, we have developed and applied novel techniques that allow direct linking of process rates to the identity and biomass of the organisms involved. Monitoring data and process studies have been used in numerical models to integrate the various biogeochemical cycles and to advance our understanding of the evolving estuarine filter function of the Scheldt estuary

Vijftig jaar monitoring en beheer van de Friese en Groninger kwelderwerken: 1960-2009

Dit WOt-werkdocument is een update van het kwelderboek uit 2001 en gaat ook over de bescherming door de kwelderwerken tegen de Allerheiligenvloed van 2006, over de Kaderrichtlijn Water en over de Sylt Conferentie van 2010. In 2007 verscheen in de WOT IN serie al een deel over Monitoring van kwelders in de Waddenzee, met beheermaatregelen voor alle kwelders (www.waddenzee.nl/Kwelders.1982.0.html). In de publicaties is ook aandacht voor beweiding, vegetatiekaarten, veroudering van de vegetatie, zeegras, grondwerk, ontwatering, en duurzaamheid van de rijshoutdammen

Friese en Groninger kwelderwerken : monitoring en beheer 1960-2010

Zowel in nationaal als in trilateraal verband geldt als één van de ecologische doelen voor de Waddenzee een zo groot en natuurlijk mogelijk areaal aan kwelders. Actief ingrijpen om bestaande kwelders in stand te houden dient op een zo natuurlijk mogelijke wijze plaats te vinden. In de kwelderwerken en zomerpolders langs Friese en Groninger vastelandskust is een omslag in beheer ingezet richting duurzamer en minder kunstmatig. Langetermijnmonitoring van onder meer de hoogte- en vegetatieontwikkeling begeleidt deze verandering en dient ook om te zien of de meer natuurlijke wijze van beheer zich verdraagt met de effecten van zeespiegelstijging. De resultaten worden jaarlijks op www.waddenzee.nl gepubliceerd en zijn verder onder andere ook input voor de vijfjaarlijkse Quality Status Reports in het kader van de trilaterale samenwerking tussen de Wadddenzee-landen. De Waddenzee is het belangrijkste gebied voor éénjarige pioniervegetaties van Zeekraal. Deze pionierzone is de overgang van wadplaten naar kwelder en beschermt de hoger gelegen kwelderzones. Door opslibbing worden kwelders hoger, waarbij de vegetatie door successie verandert. De vegetatie ontwikkelt zich tijdens dat proces tot een eindstadium of climaxbegroeiing. De biodiversiteit neemt sterk af als een kwelder in zijn eindfase komt door veroudering met als eindstadium een soortenarme vegetatie van Zeekweek. Begreppeling versnelt de veroudering van de kwelderzone. Beweiding stelt de ontwikkeling van een climaxvegetatie uit. De ideale natuurlijke situatie zou cyclische successie zijn, daarbij zijn aangroei en afslag van kwelders in evenwicht. De kwaliteit van kwelders kan worden verbeterd door de variatie aan hoogtezones, geomorfologische vormen (groene stranden, slufters, zandige kwelders, kleiige kwelders) en beheervormen (beweide en onbeweide kwelders) te behouden of te herstelle

Industrial survey for associated species: Results of a pilot-year

To increase scientific knowledge and stimulate discussion on management of data-limited species, Ekofish Group B.V., the North Sea Foundation (NSF) and IMARES started a research project. This project consisted of two phases. In the first phase, IMARES and NSF performed a literature study on the constrains in management and biological knowledge for species selected by Ekofish. After phase one, Ekofish Group B.V. requested IMARES to set up an industrial survey to gather more information on turbot, brill and lemon sole. A pilot-survey was designed and performed for these species to test whether an industrial survey is feasible and valuable for biological knowledge and if so, how this survey should be designed. To test the design of the survey, research will be done on the haul duration and mesh size. To examine the added value of the pilot survey, results are compared with the BTS. In this report, the results of this pilot survey are presented and answer will be given to the following research question: “Is an industrial survey for turbot, bill and lemon sole feasible and does it increase knowledge with respect to scientific surveys?

Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections

The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozide's and Fluspirilene's efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.Immunogenetics and cellular immunology of bacterial infectious disease

Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a common feature in trisomic placentas?

Objective: Non-invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed. Method: NIPT was conducted in the course of the Dutch TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core of two to four placental chorionic villi biopsies were studied with single nucleotide polymorphism (SNP) array. Clinical outcome data were collected. Results: In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three cell lines were present in the placenta, whereas BPD was found in AF. In 1/3 cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was found in the placenta. Five of 10 pregnancies were affected with pre-eclampsia, low birth weight, preterm delivery, and/or congenital malformations. Conclusion: The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated proves that trisomic zygote rescue may involve multiple rescue events during early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may explain the abnormal phenotype in undiagnosed cases

Chain-computerisation, quality and risk

This article is available in English and DutchThe theoretical framework of Chain-computerisation provides insight into social chains and helps to create chain communication systems by tackling a so–called dominant chain problem (the problem that forces the parties within the chain to work together). If the quality of the chain information system and the quality of the data critical for the chain communication are sub-standard, the dominant chain problem cannot be adequately addressed. In this article, a deepening of the quality dimension of the theory of Chain-computerisation will be mapped out which could help create a reliable chain solution. Moreover, we will discuss how the theoretical framework steers us in the determination of the essential quality of a chain information system and the data that is processed by it

Governance and financial aspects of chain-collaboration: Lessons from practice

The characteristics of chain environments have an influence on the way parties collaborate. In this article, two practical cases are described: (1) a program for optimizing administrative and logistic processes for the export chain of agricultural goods from the Netherlands to non-EU-countries and (2) a program for optimizing the chain of soil-monitoring for potato eelworm disease. These cases show examples of the way chain-collaboration is established in practice and governance and financial issues that arise. In the conclusion, based on the cases, we present several guidelines that might help to avoid/overcome the governance and financial issues in a chain-optimization project or program

On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy

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