In vitro and in vivo Staining Characteristics of Small,Fluorescent, Aβ42‐Binding D‐Enantiomeric Peptides in Transgenic AD Mouse Models

Plaque visualisation : We identified three different D ‐enantiomeric peptides that bind to Alzheimer's amyloid β (Aβ1‐42). As there is currently no definitive pre‐mortem diagnosis for Alzheimer's disease, we investigated the peptides' suitability as molecular probes for in vivo imaging in transgenic mouse models.

     

Key to analyte migration and retention in electrochromatography

This work identifies electrical field-induced concentration polarization (CP) as a key physical mechanism influencing the retention behavior of charged analytes in electrochromatography with fixed beds of porous adsorbent particles. Due to an insufficient screening of intraparticle surface charge, under most general conditions the porous (permeable) particles become charge-selective. CP is caused by coupled mass and charge transport normal to the charge-selective external surface of the permeable particles, which leads to concentration gradients of ionic species in the adjoining interparticle electrolyte solution. Cation-exchange (cation-selective) particles were employed to investigate the influence of applied voltage on the retention factor of counterionic, i.e., positively charged, analytes. It is demonstrated by macroscopic retention data and microscopic studies resolving the CP phenomenon on a particle scale that the dependence of CP on electrical field and mobile-phase ionic strengths is directly reflected in concomitant changes of analyte retention. The CP zones that develop at the interface between interparticle and intraparticle pore space are recognized by charged, but not electroneutral analytes while entering or leaving the particles. The intensity of these convective-diffusion boundary layers (CP zones) depends on the applied field strength and charge selectivity of a particle. Thus, it is the charge-selective transport between the interparticle and intraparticle pore space in packed beds that prevails under typical experimental conditions in electrochromatography and that forms the physical basis for a general electrical field dependence of the retention factor of charged analytes.     

Using perturbation theory to compute the morphological similarity of diffusion tensors

Computing the morphological similarity of diffusion tensors (DTs) at neighboring voxels within a DT image, or at corresponding locations across different DT images, is a fundamental and ubiquitous operation in the postprocessing of DT images. The morphological similarity of DTs typically has been computed using either the principal directions (PDs) of DTs (i.e., the direction along which water molecules diffuse preferentially) or their tensor elements. Although comparing PDs allows the similarity of one morphological feature of DTs to be visualized directly in eigenspace, this method takes into account only a single eigenvector, and it is therefore sensitive to the presence of noise in the images that can introduce error intothe estimation of that vector. Although comparing tensor elements, rather than PDs, is comparatively more robust to the effects of noise, the individual elements of a given tensor do not directly reflect the diffusion properties of water molecules. We propose a measure for computing the morphological similarity of DTs that uses both their eigenvalues and eigenvectors, and that also accounts for the noise levels present in DT images. Our measure presupposes that DTs in a homogeneous region within or across DT images are random perturbations of one another in the presence of noise. The similarity values that are computed using our method are smooth (in the sense that small changes in eigenvalues and eigenvectors cause only small changes in similarity), and they are symmetric when differences in eigenvalues and eigenvectors are also symmetric. In addition, our method does not presuppose that the corresponding eigenvectors across two DTs have been identified accurately, an assumption that is problematic in the presence of noise. Because we compute the similarity between DTs using their eigenspace components, our similarity measure relates directly to both the magnitude and the direction of the diffusion of water molecules. The favorable performance characteristics of our measure offer the prospect of substantially improving additional postprocessing operations that are commonly performed on DTI datasets, such as image segmentation, fiber tracking, noise filtering, and spatial normalization.     

Polycyclic aromatic hydrocarbons (PAH) in various types of tea

For the analysis of the 16 PAH (EFSA-PAH), which are classified as priority for different food groups by the Scientific Committee on Food (SCF) and the Joint FAO/WHO Experts Committee on Food Additives (JECFA) in tea, a sensitive analytical Fast-GC/HRMS method was used. The sample preparation included accelerated solvent extraction (ASE) and the highly automated clean up steps, gel permeation chromatography and solid phase extraction. The analytical parameters, limit of detection (0.01–0.02 μg/kg) and limit of quantification (0.03–0.06 μg/kg), were determined. The repeatability (RSD, n = 3) of different PAH in fruit tea ranged from 0.1 to 11%. It was observed that the total contents of the 16 PAH in tea samples ranged from 14 to 2,662 μg/kg. The analysed tea samples showed an increasing presence of PAH in the following order: herbal and fruit tea (n = 7) < black tea (n = 11) < green tea (n = 11) < white tea (n = 3) < mate-tea (n = 8). The correlation coefficient (R) between BaP and the sum of the 16 EFSA-PAH was established considering the contamination amount in all the 40 tea samples analysed.     

Furan and Methylfurans in Foods: An Update on Occurrence,Mitigation, and Risk Assessment

The acceptance of many foods is related to traditional cooking practices, which create taste and texture and are important to digestibility, preservation, and the reduction of foodborne illnesses. A wide range of compounds are formed during the cooking of foods, a number of these have been shown to lead to adverse effects in classical toxicological models and are known as food processing contaminants (FPC). It is essential that the presence and effects of such compounds alone and in combination within the diet are understood such that proportionate risk management measures can be developed, while taking a holistic view across the whole value chain. Furan and alkylfurans (principally 2‐ and 3‐methylfuran) are highly volatile FPC, which are formed in a wide range of foods at low amounts. The focus of research to‐date has been on those foods, which have been identified to be most consequential in terms of being sources of exposure, namely jarred and canned foods for infants and young children (meals and drinks) and coffee (roast and ground, soluble). This report presents (i) new industry data on the occurrence of furan and methylfurans in selected food categories following previous coffee studies, (ii) the most salient parameters that impact furan formation, and (iii) aspects of importance for the risk assessment.     

RNA Dynamics by NMR Spectroscopy

An ever-increasing number of functional RNAs require a mechanistic understanding. RNA function relies on changes in its structure, so-called dynamics. To reveal dynamic processes and higher energy structures, new NMR methods have been developed to elucidate these dynamics in RNA with atomic resolution. In this Review, we provide an introduction to dynamics novices and an overview of methods that access most dynamic timescales, from picoseconds to hours. Examples are provided as well as insight into theory, data acquisition and analysis for these different methods. Using this broad spectrum of methodology, unprecedented detail and invisible structures have been obtained and are reviewed here. RNA, though often more complicated and therefore neglected, also provides a great system to study structural changes, as these RNA structural changes are more easily defined—Lego like—than in proteins, hence the numerous revelations of RNA excited states.     

Intramammary infusion of a live culture for treatment of bovine mastitis: effect of live lactococci on the mammary immune response

In the accompanying article, we demonstrated that a live culture of Lactococcus lactis compares favourably with antibiotics for treatment of bovine mastitis in two initial field trials. In an effort to explain the mechanism involved, this study investigated the effect of culture administration on the local immune response. In this respect we initially observed that infusion of the live culture Lactococcus lactis stimulated substantial recruitment of polymorphonucleocytes (PMN) and lymphocytes to the udder. For instance, in one assay, quarters infused with the probiotic experienced a dramatic increase (approximately 20,000-fold) in neutrophils over the first 48-h period from an average value of 83.6 cells/ml pre-treatment to 1.78 x 106 cells/ml 48 h post-infusion. Levels of the acute phase proteins haptaglobin and milk amyloid A were also elevated significantly in comparison with controls following infusion of the culture. The results of flow cytometric assays also demonstrated that while infusion of a live lactococcal culture led to an enhanced recruitment of PMN to the udder (from 1.85 x 104 cells/ml pre-infusion to 1.45 x 106 cells/ml 24 h post-infusion) cell-free supernatant from the same culture was not able to do so, indicating that live Lc. lactis can specifically trigger the mammary immune response to elicit PMN accumulation. These results suggest that the mechanism responsible for this probiotic treatment of mastitis is associated with stimulation of the host intramammary immune system.     

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

α_vβ₆ Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with α_vβ₆ integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the α_vβ₆-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH₂) to enhance α_vβ₆ integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)₃ showed a 28-fold higher α_vβ₆ affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC₅₀ of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC₅₀-based selectivity over the related integrin α_vβ₈ (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)₃ holds promise for improved clinical PET diagnostics of carcinomas and fibrosis.     

Bio-based polyurethane films using white dextrins

Several new eco-friendly materials have the potential to replace conventional petroleum-derived materials and monomers. Among them are natural polysaccharides. The use of polysaccharides in polyurethane (PU) synthesis has not yet been studied extensively, even though as multihydroxyl compounds, they can easily serve as crosslinkers in PU synthesis. One naturally occurring (hyper-)branched polymer is amylopectin, a component of starch. In this work, we report the PU synthesis and film-forming capacity using the asymmetric cyclic aliphatic diisocyanate—isophorone diisocyanate (IPDI) with acetylated and pristine partially hydrolyzed amylopectin/white dextrin (AVEDEX W80) as a crosslinker. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47454.