Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Fire safe,sustainable loose furnishing

The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production.     

Autolysis and the endogenous proteinases characterised in beardless barb (Anematichthys apogon) muscle

Beardless barb is a common fish species used in fermentation of fish paste Ka-pi-plaa. Autolytic profile of beardless barb muscle showed the maximum autolysis was at 50 °C, at both acidic and alkaline pH values. With augmentation concentration of NaCl, autolytic activity slightly decreased. Endogenous proteinases isolated from fish muscle in crude extract forms were also characterised. The acidic proteinases had optimum activity at pH 3.0 and 50°C, and they showed higher proteolytic activity than the alkaline proteinases which were optimally active at pH 9.0 and 50 °C. Proteinases in peak at pH 3.0 were inhibited by pepstatin A, but those in peak at pH 9.0 were highly inhibited by PMSF, TLCK and soybean trypsin inhibitor, suggesting that both aspartic and serine proteinases were existed in beardless barb muscle. The proteinases were stable in pH range of 2.0-5.0 but unstable at the temperatures higher than 40 °C. NaCl suppressed the proteolytic activity, ATP activated the proteinase activity, while CaCl₂, MgCl₂ and CoCl₂ exhibited no influence on the activity. The results implied that cathepsin D is the predominant proteinase responsible for autolysis in beardless barb. The findings were useful to improve the processing and qualities of Ka-pi-plaa product using beardless barb as raw material.     

Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides

The innate immune system's interaction with bacterial cells plays a pivotal role in a variety of human diseases. Carbohydrate units derived from a component of bacterial cell wall, peptidoglycan (PG), are known to stimulate an immune response. Nonetheless, access to modified late-stage peptidoglycan intermediates is limited due to their synthetic complexity. A method to rapidly functionalize PG fragments is needed to better understand the natural host–PG interactions. Here methyl N,O-hydroxylamine linkers are incorporated onto a synthetic PG derivative, muramyl dipeptide (MDP). The modification of MDP maintained the ability to stimulate a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) immune response dependent on the expression of nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Intrigued by this modification's maintenance of biological activity, several applications were explored. Methyl N,O-hydroxylamine MDP was amendable to N-hydroxylsuccinimide (NHS) chemistry for bioconjugation to fluorophores as well as a self-assembled monolayer for Nod2 surface plasmon resonance analysis. Finally, linker incorporation was applicable to larger PG fragments, both enzymatically generated from Escherichia coli or chemically synthesized. This methodology provides rapid access to PG probes in one step and allows for the installation of a variety of chemical handles to advance the molecular understanding of PG and the innate immune system.     

Airport Road Access at Planet Scale using Population Grid and Openstreetmap

Networks and Spatial Economics - A new comparative framework for estimating the road access of airports around the world at high resolution is proposed. While existing studies are spatially...     

Alternating Cationic-Hydrophobic Peptide/Peptoid Hybrids: Influence of Hydrophobicity on Antibacterial Activity and Cell Selectivity

The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC₅₀>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation.     

„Die kommen alle her und gaffen.“ Hohes Körpergewicht als medizinische,ethische und gesellschaftliche Herausforderung

Ethik in der Medizin -     

Anomalous kinetics of lath martensite formation in stainless steel

The kinetics of lath martensite formation in Fe–17·3 wt-%Cr–7·1 wt-%Ni–1·1 wt-%Al–0·08 wt-%C stainless steel was investigated with magnetometry and microscopy. Lath martensite forms during cooling, heating and isothermally. For the first time, it is shown by magnetometry during extremely slow isochronal cooling that transformation rate maxima occur, which are interrupted by virtually transformation free temperature regions. Microscopy confirms martensite formation after athermal nucleation of clusters followed by their time dependent growth. The observations are interpreted in terms of time dependent autocatalytic lath martensite formation followed by mechanical stabilisation of austenite during the transformation process.     

Sensory characteristics and storage quality indicators of surimi franks nutritionally enhanced with omega‐3 rich flaxseed oil and salmon oil

Surimi franks were fortified with flaxseed or salmon oil at 2 g/100 g sample, franks without added oil served as a control. Thiobarbituric acid reactive substances values were highest (P < 0.001) in salmon oil franks; however, these values did not change over the 21‐day storage period regardless of frank type (P > 0.05). Frank pH decreased over time (P = 0.011) for all frank types. There were differences in textural properties between frank types (P < 0.05), with the flaxseed franks being softer and less gummy, cohesive and chewy than the control franks. Participants (n = 79; age 18–35) evaluated visual appeal, colour, aroma, texture, flavour and acceptability on a hedonic scale; there were no differences (P > 0.05) between franks. Fifty‐four panellists reported consuming sausage on a weekly to monthly basis, and most (50/79) indicated interest in purchasing this type product. The surimi franks were accepted by young adult consumers, which may indicate market potential of these types of products.