Neutralizing Nanobodies Targeting Diverse Chemokines Effectively Inhibit Chemokine Function

Chemokine receptors and their ligands play a prominent role in immune regulation but many have also been implicated in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, allograft rejection after transplantation, and also in cancer metastasis. Most approaches to therapeutically target the chemokine system involve targeting of chemokine receptors with low molecular weight antagonists. Here we describe the selection and characterization of an unprecedented large and diverse panel of neutralizing Nanobodies (single domain camelid antibodies fragment) directed against several chemokines. We show that the Nanobodies directed against CCL2 (MCP-1), CCL5 (RANTES), CXCL11 (I-TAC), and CXCL12 (SDF-1α) bind the chemokines with high affinity (at nanomolar concentration), thereby blocking receptor binding, inhibiting chemokine-induced receptor activation as well as chemotaxis. Together, we show that neutralizing Nanobodies can be selected efficiently for effective and specific therapeutic treatment against a wide range of immune and inflammatory diseases.     

Flugunfähigmachen von Vögeln – Für und Wider

The techniques and biological functions of avian flight are briefly presented. The reasons for rendering zoo birds flightless are explained taking into account the tasks and obligations of modern zoos, and the various deflighting procedures are described. The legal situation regarding deflighting as it currently exists in Germany and other countries is clarified. It is discussed in detail under which circumstances it would be justifiable to render a bird flightless, to what extent keeping the birds in aviaries would be an alternative and whether reversible or irreversible methods should be preferred. A legal opinion has been sought which came to the conclusion that even under the restrictive Animal Welfare Law of Germany interventions to render a bird flightless were admissible if based on veterinary indication on a case-by-case basis. Such indication may be justified by the anticipation that a bird may be injured or die from an accident in future if not deflighted. Contrary to the views of some legal experts commenting on the German Animal Welfare Law the authors consider feather clipping not to be an intervention prohibited under the law. In the interest of the good functioning of european and international breeding programmes the authors suggest that the German legislation should be modified with a view of containing a general derogation for rendering flightless at least certain species of zoo birds.     

The advantage of laser‐capture microdissection over whole tissue analysis in proteomic profiling studies

Laser‐capture microdissection (LCM) offers a reliable cell population enrichment tool and has been successfully coupled to MS analysis. Despite this, most proteomic studies employ whole tissue lysate (WTL) analysis in the discovery of disease biomarkers and in profiling analyses. Furthermore, the influence of tissue heterogeneity in WTL analysis, nor its impact in biomarker discovery studies have been completely elucidated. In order to address this, we compared previously obtained high resolution MS data from a cohort of 38 breast cancer tissues, of which both LCM enriched tumor epithelial cells and WTL samples were analyzed. Label‐free quantification (LFQ) analysis through MaxQuant software showed a significantly higher number of identified and quantified proteins in LCM enriched samples (3404) compared to WTLs (2837). Furthermore, WTL samples displayed a higher amount of missing data compared to LCM both at peptide and protein levels (p‐value < 0.001). 2D analysis on co‐expressed proteins revealed discrepant expression of immune system and lipid metabolisms related proteins between LCM and WTL samples. We hereby show that LCM better dissected the biology of breast tumor epithelial cells, possibly due to lower interference from surrounding tissues and highly abundant proteins. All data have been deposited in the ProteomeXchange with the dataset identifier PXD002381 ( http://proteomecentral.proteomexchange.org/dataset/PXD002381 ).     

Establishment and Early Growth of Willow at Different Levels of Weed Competition and Nitrogen Fertilization

To evaluate the effects of weed competition and nitrogen fertilization on the early growth performance of willow, cuttings of the clone Tora (Salix schwerinii x S. viminalis) were planted in buckets together with model weeds (spring barley or white mustard) sown 15, 26, and 30 days after willow planting. The buckets were fertilized with 30 or 90 kg N ha^?1. Willow with weeds sown after 15 days produced less biomass and smaller leaf area and had a lower maximum shoot height compared to willow planted without weeds and willow with weeds sown after 26 or 30 days. Fertilization with 90 kg N ha^?1 gave higher willow biomass production in willow with weeds sown after 26 or 30 days. Type of model weed had no effect on willow performance. Weed biomass and maximum shoot height were higher in weeds planted without willows compared to the willow-weed mixtures. A high nitrogen level gave more weed biomass when planted without willows and in the willow-weed mixture with weeds sown after 15 days. We conclude that for the given high density of willow, competition from weeds emerging soon after willow planting had strong effect on early production. Furthermore, if there is a risk of weed infestation, fertilization should be delayed.     

Lesser Black-backed Gulls Larus fuscus thriving on a non-marine diet

Capsule: Lesser Black-backed Gulls Larus fuscus breeding 30?km from the coast in the Netherlands focussed entirely on terrestrial food sources and reached relatively high breeding success.

Aim: To gain insight in the foraging ecology, habitat use and breeding performance of inland-breeding Lesser Black-backed Gulls.

Methods: We received data from seven birds fitted with global positioning system (GPS) loggers. The colony was frequently visited to collect pellets and boluses and to monitor reproductive success, mortality and growth rate of chicks.

Results: The GPS data revealed that mainly terrestrial habitats were used, 98% of these GPS positions were within 25?km of the colony. Refuse dumps were the most preferred sites, but also agricultural fields and freshwater bodies were often visited. Only two of the 710 recorded trips were directed to the North Sea. The pellet and bolus analyses confirmed the GPS data: no marine food remains were found. Breeding success of birds in the enclosure was relatively high, with 90% of eggs hatched and 51% of chicks fledged (1.6 chicks/pair).

Conclusions: Relying on terrestrial food is feasible when sources are available in the vicinity of the colony. We conclude that Lesser Black-backed Gulls could theoretically shift towards inland breeding after a fishery discards ban.     

The nature of plant adaptations to salinity stress has trophic consequences

In different ecosystems herbivores highly prefer particular plant species. This is often explained in a stoichiometric framework of nutrient‐based plant adaptations to herbivory. We hypothesize that such super‐palatability can also arise as an evolutionary by‐product of osmoregulatory adaptations of plants to stressful environmental conditions, as salinity, drought and cold. Here, we investigate in a coastal salt marsh why some plant species are highly preferred by migratory brent geese Branta bernicla bernicla in spring while others are avoided. This salt marsh is an important spring staging site for the geese. Sufficient energy storage in a short period is critical to enable their northward migration to Siberia and subsequent reproduction. We test if geese prefer plants that balance their internal osmotic potential with the saline environment through energy‐rich soluble sugars over plant species that use (compartmentalized) salts for this. We find that plant nitrogen and acid detergent fiber content, classic predictors of herbivore preferences, poorly explain which plants the geese prefer. Instead, plant species that are highly preferred by the geese adapt to salinity by high soluble sugar concentrations while avoided species do this by high plant salt concentrations. Thus, the type of osmoregulatory adaptation to stress displayed by different plant species is a good predictor for the food preference of geese on this salt marsh. We suggest that variation in other types of osmoregulation‐based stress adaptations, as plant cold adaptations in tundras and plant drought adaptations in savannas, have similar important consequences for trophic interactions.     

Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors

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