Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells

Adipose-derived mesenchymal stem/stromal cells (ASCs) are an adult stem cell population able to self-renew and differentiate into numerous cell lineages. ASCs provide a promising future for therapeutic angiogenesis due to their ability to promote blood vessel formation. Specifically, their ability to differentiate into endothelial cells (ECs) and pericyte-like cells and to secrete angiogenesis-promoting growth factors and extracellular vesicles (EVs) makes them an ideal option in cell therapy and in regenerative medicine in conditions including tissue ischemia. In recent angiogenesis research, ASCs have often been co-cultured with an endothelial cell (EC) type in order to form mature vessel-like networks in specific culture conditions. In this review, we introduce co-culture systems and co-transplantation studies between ASCs and ECs. In co-cultures, the cells communicate via direct cell–cell contact or via paracrine signaling. Most often, ASCs are found in the perivascular niche lining the vessels, where they stabilize the vascular structures and express common pericyte surface proteins. In co-cultures, ASCs modulate endothelial cells and induce angiogenesis by promoting tube formation, partly via secretion of EVs. In vivo co-transplantation of ASCs and ECs showed improved formation of functional vessels over a single cell type transplantation. Adipose tissue as a cell source for both mesenchymal stem cells and ECs for co-transplantation serves as a prominent option for therapeutic angiogenesis and blood perfusion in vivo.     

Cross-Sectional Associations of Food Consumption with Plasma Fatty Acid Composition and Estimated Desaturase Activities in Finnish Children

Plasma fatty acid (FA) composition is known to be an indicator of dietary fat quality, but the associations of other dietary factors with plasma FA composition remain unknown in children. We investigated the cross-sectional associations of food consumption with the proportions of FA and estimated desaturase activities in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The subjects were a population sample of 423 children aged 6–8 years examined at baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We assessed food consumption by food records and plasma FA composition by gas chromatography. We used linear regression models adjusted for age, sex, physical activity and total energy intake to analyze the associations. A higher consumption of vegetable oil-based margarine (fat 60–80 %) was associated with a higher proportion of linoleic and α-linolenic acids in plasma CE and PL. A higher consumption of high-fiber grain products was related to a lower proportion of oleic acid in CE and PL. The consumption of candy was directly associated with the proportion of palmitoleic and oleic acid in plasma CE. The consumption of vegetable oil-based margarine was inversely associated with estimated stearoyl-CoA-desaturase activity in plasma CE and PL and the consumption of candy was directly related to it in plasma CE. The results of our study suggest that plasma FA composition is not only a biomarker for dietary fat quality but also reflects the consumption of high-fiber grain products and foods high in sugar among children.     

Efficient Enzymatic Cyclization of Disulfide-Rich Peptides by Using Peptide Ligases

Disulfide-rich macrocyclic peptides—cyclotides, for example—represent a promising class of molecules with potential therapeutic use. Despite their potential their efficient synthesis at large scale still represents a major challenge. Here we report new chemoenzymatic strategies using peptide ligase variants—inter alia, omniligase-1—for the efficient and scalable one-pot cyclization and folding of the native cyclotides MCoTI-II, kalata B1 and variants thereof, as well as of the θ-defensin RTD-1. The synthesis of the kB1 variant T20K was successfully demonstrated at multi-gram scale. The existence of several ligation sites for each macrocycle makes this approach highly flexible and facilitates both the larger-scale manufacture and the engineering of bioactive, grafted cyclotide variants, therefore clearly offering a valuable and powerful extension of the existing toolbox of enzymes for peptide head-to-tail cyclization.     

Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism

Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M₁-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M₁ positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.     

A process for designing algorithm-based personalized gamification

Multimedia Tools and Applications - Personalization is an upcoming trend in gamification research, with several researchers proposing that gamified systems should take personal characteristics into...     

Fast Voronoi modeling

The common way to construct Voronoi tessellations is to compare the distances between given reference points using a given distance function. To generalize this distance-function concept we expand an existing approach which defines distance functions by their ``unit circles'. Our new approach allows modeling the ``unit circles' by a closed Spline curve. Changing the control polygon directly affects the tessellation's appearance. Typically generalized Voronoi diagrams are represented by Voronoi vertices and curves separating the individual tiles. To obtain interactive modeling we extended an existing hardware accelerated rendering approach computing a bitmap-representation using different colors for individual tiles. With our extension, we are able to use our Spline distance representations as input for a growing process. This growing process easily takes into account weighting approaches like multiplicative, additive, and even free functional weighting.     

Incremental constraint modelling in a feature modelling system

The techniques of constraint propagation have recently been successfully applied to feature-based design. Because of their speed, constraint propagation methods allow incremental design and rapid local modifcations of the part. However, cyclic constraints cause serious problems to current constraint propagation algorithms. Variational geometric design systems can, in principle, manage these cases. Unfortunately, this typically requires complete re-evaluation of the underlying set of constraint equations, making the method unsuitable for interactive use. The proposed system aims to localize the problem of constraint solving and maintenance. The constraint graph of the part or assembly is divided into several independent partial graphs, subsystems. Afterwards, each subsystem is handled separately using a selected constraint solving technique for the subsystem.     

UR: SMART–A tool for analyzing social media content

Information Systems and e-Business Management - The digital transformation, with its ongoing trend towards electronic business, confronts companies with increasingly growing amounts of data which...     

On the realization of periodic functions

In this article, canonical and spectrally minimal infinite-dimensional state space realizations for periodic functions are considered. It is shown that the periodic functions having ℓ₁ Fourier coefficients are precisely those realizable by a Riesz spectral system (RSS) in which the system operator generates a periodic strongly continuous semigroup and the observation operator is bounded. This realization can easily be converted to a canonical and spectrally minimal form. It is shown how the use of RSS and Cesáro sums of Fourier series allows the construction of a state space realization for a given periodic function merely integrable over its period. Simple finite-dimensional approximations with error bounds are derived for the RSS realization. Regular well-posed linear systems (WPLS) are used to construct a Fuhrmann-type realization for a given periodic function integrable over its period. It is shown that the RSS realizations and WPLS realizations are precisely equally good at coping with the possible ill behavior of a given bounded periodic function integrable over its period, but the WPLS realization is not always spectrally minimal or canonical.