Ultrathin Polydopamine Films with Phospholipid Nanodiscs Containing a Glycophorin A Domain

Cellular membranes have long served as an inspiration for nanomaterial research. The preparation of ultrathin polydopamine (PDA) films with integrated protein pores containing phospholipids and an embedded domain of a membrane protein glycophorin A as simplified cell membrane mimics is reported. Large area, ultrathin PDA films are obtained by electropolymerization on gold surfaces with 10–18 nm thickness and dimensions of up to 2.5 cm². The films are transferred from gold to various other substrates such as nylon mesh, silicon, or substrates containing holes in the micrometer range, and they remain intact even after transfer. The novel transfer technique gives access to freestanding PDA films that remain stable even at the air interfaces with elastic moduli of ≈6–12 GPa, which are higher than any other PDA films reported before. As the PDA film thickness is within the range of cellular membranes, monodisperse protein nanopores, so‐called “nanodiscs,” are integrated as functional entities. These nanodisc‐containing PDA films can serve as semi‐permeable films, in which the embedded pores control material transport. In the future, these simplified cell membrane mimics may offer structural investigations of the embedded membrane proteins to receive an improved understanding of protein‐mediated transport processes in cellular membranes.     

Nanomaterial Transformations in the Environment: Effects of Changing Exposure Forms on Bioaccumulation and Toxicity

In the environment, nanomaterials (NMs) are subject to chemical transformations, such as redox reactions, dissolution, coating degradation, and organic matter, protein, and macromolecule binding, and physical transformations including homo or heteroagglomeration. The combination of these reactions can result in NMs with differing characteristics progressing through a functional fate pathway that leads to the formation of transformed NM functional fate groups with shared properties. To establish the nature of such effects of transformation on NMs, four main types of studies are conducted: 1) chemical aging for transformation of pristine NMs; 2) manipulation of test media to change NM surface properties; 3) aging of pristine NMs water, sediment, or soil; 4) NM aging in waste streams and natural environments. From these studies a paradigm of aging effects on NM uptake and toxicity can be developed. Transformation, especially speciation changes, largely results in reduced potency. Further reactions at the surface resulting in processes, such as ecocorona formation and heteroagglomeration may additionally reduce NM potency. When NMs of differing potency transform and enter environments, common transformation reaction occurring in receiving system may act to reduce the variation in hazard between different initial NMs leading to similar actual hazard under realistic exposure conditions.     

Photoderivatized polymer thin films at quartz crystal microbalance surfaces: sensors for carbohydrate-protein interactions

Photoderivatized polymer-coated gold surfaces have been developed following a perfluorophenylazide-based double ligation strategy. Gold-plated quartz crystal microbalance (QCM) crystals were initially covalently functionalized with a monolayer of poly(ethylene glycol) (PEG), using photo- or thermolytic nitrene formation and insertion. The polymer surfaces were subsequently used as substrates for photoinsertion of carbohydrate-derivatized photoprobes, yielding different recognition motifs for selective protein binding. The resulting robust and biocompatible sensor surfaces were applied to a flow-through QCM instrument for monitoring lectin-carbohydrate interactions in real time. The results clearly show the predicted lectin selectivity, demonstrating the applicability of the approach.     

Human CD22-Transgenic,Primary Murine Lymphoma Challenges Immunotherapies in Organ-Specific Tumor Microenvironments

Targeted immunotherapies have greatly changed treatment of patients with B cell malignancies. To further enhance immunotherapies, research increasingly focuses on the tumor microenvironment (TME), which differs considerably by organ site. However, immunocompetent mouse models of disease to study immunotherapies targeting human molecules within organ-specific TME are surprisingly rare. We developed a myc-driven, primary murine lymphoma model expressing a human-mouse chimeric CD22 (h/mCD22). Stable engraftment of three distinct h/mCD22⁺ lymphoma was established after subcutaneous and systemic injection. However, only systemic lymphoma showed immune infiltration that reflected human disease. In this model, myeloid cells supported lymphoma growth and showed a phenotype of myeloid-derived suppressor cells. The human CD22-targeted immunotoxin Moxetumomab was highly active against h/mCD22⁺ lymphoma and similarly reduced infiltration of bone marrow and spleen of all three models up to 90-fold while efficacy against lymphoma in lymph nodes varied substantially, highlighting relevance of organ-specific TME. As in human aggressive lymphoma, anti-PD-L1 as monotherapy was not efficient. However, anti-PD-L1 enhanced efficacy of Moxetumomab suggesting potential for future clinical application. The novel model system of h/mCD22⁺ lymphoma provides a unique platform to test targeted immunotherapies and may be amenable for other human B cell targets such as CD19 and CD20.     

Blackcurrant pomace from juice processing as partial flour substitute in savoury crackers: dough characteristics and product properties

Berry pomace is a by‐product of juice processing that, after drying and milling, may be used as an ingredient in cereal‐based products. This, on the one hand, not only reduces losses of edible raw material components, but also increases the nutritional value of the target food because of its high dietary fibre and bioactive compounds content. By using savoury crackers as model, this study analyses how a partial flour replacement by blackcurrant pomace (levels: 10%, 20% or 30%) affects physical properties of the respective dough (dynamic rheology in simulated baking, extensibility and adhesiveness) and characteristics of the baked product (colour, texture and sensory properties). Pomace addition significantly affected both systems. By considering the high moisture absorption capacity of this material through water level adaptation in formulations and by only substituting gluten‐free flour (which led to a constant gluten content), it is demonstrated that even a flour replacement of up to 30% leads to acceptable products. A restrained protein development was observed in pomace containing dough, leading to a lower extensibility, and to reduced volume increase and lower breaking force after baking. In contrast, dough handling and sensory acceptance were not corrupted by pomace application even though colour of the final product was changed to a great extent.     

Unexplained site variance in machine strength grading of Norway spruce structural timber

The aim of the study was to assess site effects in terms of unexplained site variance in machine strength grading of Norway spruce structural timber. The site effects were estimated for grading based on axial resonance frequency and timber length, and for grading based on dynamic modulus of elasticity. Timber was collected from 14 sites in Norway, and linear mixed models were developed based on 1188 boards. The study showed that strength grading based on axial resonance frequency and timber length leaves out effects of site that are related to altitude, latitude and site index. The variance could be reduced when the grading was based on dynamic modulus of elasticity. For both grading methods, the site effects were smaller for bending strength than for modulus of elasticity and density. Major parts of the site effects were explained by mass density, and simulations showed that it is possible to fulfil the requirements of the strength classes with a higher yield when the sorting is based on a combination of exclusion by mass density and exclusion by the frequency-based indicating property.