Porcine Sialoadhesin (CD169/Siglec-1) Is an Endocytic Receptor that Allows Targeted Delivery of Toxins and Antigens to Macrophages

Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab')2 fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin- and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages

Hydroponic technologies

This open access book, written by world experts in aquaponics and related technologies, provides the authoritative and comprehensive overview of the key aquaculture and hydroponic and other integrated systems, socio-economic and environmental aspects. Aquaponic systems, which combine aquaculture and vegetable food production offer alternative technology solutions for a world that is increasingly under stress through population growth, urbanisation, water shortages, land and soil degradation, environmental pollution, world hunger and climate change.Hydroponics is a method to grow crops without soil, and as such, these systems are added to aquaculture components to create aquaponics systems. Thus, together with the recirculating aquaculture system (RAS), hydroponic production forms a key part of the aqua-agricultural system of aquaponics. Many different existing hydroponic technologies can be applied when designing aquaponics systems. This depends on the environmental and financial circumstances, the type of crop that is cultivated and the available space. This chapter provides an overview of different hydroponic types, including substrates, nutrients and nutrient solutions, and disinfection methods of the recirculating nutrient solutions

AGORA, a data- and biobank for birth defects and childhood cancer

Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection.status: publishe

Laser Doppler flowmetry

An early determination of pulpal vitality is crucial with respect to a correct differential diagnosis of revascularisation or necrosis and its treatment. The use of sensibility tests (cold, heat, electric pulp test) in combination with X-ray is commonly promoted. However, these tests are arbitrary, based on sensations, and therefore not always reliable. In such situation, registration of pulpal blood flow will be more than an added value. The most studied and well-documented method for registration of pulpal blood flow is laser Doppler flowmetry (LDF), a non-invasive technique with direct and objective registrations. In this chapter, we describe pulpal blood flow, LDF and its characteristics, this method’s advantages and disadvantages and recent developments regarding LDF. Despite a low implementation of LDF in dentistry, this technique has proven to be an indisputable, basic asset of a dental clinic