Trends van Prioritaire Stoffen over de periode 1977 - 2002

Afhankelijk van milieuproblematiek (calamiteit), organisaties (nationaal, internationaal) en doelstellingen zijn in de loop der jaren in Nederland en daarbuiten diverse monitoringprogramma’s opgezet om inzicht te verschaffen in de aard van de milieuverontreiniging en de effecten van genomen maatregelen. Vooral accumulerende prioritaire stoffen met zeer lage gehalten in het oppervlaktewater, die door hun eigenschappen wel tot hoge concentraties in weefsels van aquatische organismen worden opgehoopt en daardoor kunnen worden gemeten, stonden hierbij sterk in de belangstelling. In opdracht van het RIWA heeft het RIVO dit rapport samengesteld over de trendmatige veranderingen in gehalten van prioritaire stoffen over de afgelopen periode van 25 jaar. Het rapport geeft een overzicht van de ontwikkeling van de waterkwaliteit, zoals deze naar voren komt uit de gehalten van prioritaire stoffen in zoetwatervis en driehoeksmossel in de Nederlandse binnenwateren. De nadruk ligt daarbij op de rivieren Rijn en Maas en hun zijtakke

Can seafood safety be compromised in the ocean of tomorrow?.

Autoria na publicação: FABIOLA FOGAÇA

July 2004 Report of Progress

Progress of each ALS-NSCORT project given by each project lead. 10 pages

Bioaccessibility of contaminants of emerging concern in raw and cooked commercial seafood species: insights for food safety risk assessment.

Autoria na publicação: FABIOLA FOGAÇA

Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome

Adeno-associated viruses (AAVs) are attractive gene therapy vectors due to their low toxicity, high stability, and rare integration into the host genome. Expressing ligands on the viral capsid can re-target AAVs to new cell types, but limited sites have been identified on the capsid that tolerate a peptide insertion. Here, we incorporated a site-specific tetracysteine sequence into the AAV serotype 9 (AAV9) capsid, to permit labelling of viral particles with either a fluorescent dye or biotin. We demonstrate that fluorescently labelled particles are detectable in vitro, and explore the utility of the method in vivo in mice with time-lapse imaging. We exploit the biotinylated viral particles to generate two distinct AAV interactomes, and identify several functional classes of proteins that are highly represented: actin/cytoskeletal protein binding, RNA binding, RNA splicing/processing, chromatin modifying, intracellular trafficking and RNA transport proteins. To examine the biological relevance of the capsid interactome, we modulated the expression of two proteins from the interactomes prior to AAV transduction. Blocking integrin αVβ6 receptor function reduced AAV9 transduction, while reducing histone deacetylase 4 (HDAC4) expression enhanced AAV transduction. Our method demonstrates a strategy for inserting motifs into the AAV capsid without compromising viral titer or infectivity

May 2004 Report of Progress

Progress of each ALS-NSCORT project given by each project lead. 11 pages

Systemic AAV vectors for widespread and targeted gene delivery in rodents

We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Perceived managerial and leadership effectiveness in UAE and Egypt: a comparison through the combined lenses of Islamic work ethics and Islamic leadership

Despite the increasing awareness that societal, sectorial, and organizational variables have a significant impact on manager and employee behavior, most studies in Asian and Middle Eastern (ME) countries, whether conducted by Western or indigenous scholars, continue to be informed by frameworks derived from the United States (US), Canada, or Western European countries (Leung, 2007; Li, 2012; Tsui, 2006) . This approach is problematic because the insights gleaned from such studies may fall only within Western theoretical constructs (Tsui, 2007; see also Shahin & Wright, 2004), thereby compromising insights regarding novel country-specific phenomena and the development of indigenous management/leadership knowledge. Consequently, many scholars (Rosenzweig, 1994; Rousseau & Fried, 2001) have called for the generation of indigenous management theories based on local conditions and socio-cultural factors, and for indigenous management and leadership research within non-Western countries (see Holtbrugge, 2013; Wolfgramm, Spiller & Voyageur, 2014; Shahin & Wright, 2004). This call is also pertinent for ME countries, where there is generally a paucity of indigenous management/leadership research and more specifically, of inductive emic (context-specific

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics