Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.     

Application of whey protein isolate in bone regeneration: Effects on growth and osteogenic differentiation of bone-forming cells

Recently, milk-derived proteins have attracted attention for applications in the biomedical field such as tissue regeneration. Whey protein isolate (WPI), especially its main component β-lactoglobulin, can modulate immunity and acts as an antioxidant, antitumor, antiviral, and antibacterial agent. There are very few reports of the application of WPI in tissue engineering, especially in bone tissue engineering. In this study, we tested the influence of different concentrations of WPI on behavior of human osteoblast-like Saos-2 cells, human adipose tissue-derived stem cells (ASC), and human neonatal dermal fibroblasts (FIB). The positive effect on growth was apparent for Saos-2 cells and FIB but not for ASC. However, the expression of markers characteristic for early osteogenic cell differentiation [type-I collagen (COL1) and alkaline phosphatase (ALP)] as well as ALP activity, increased dose-dependently in ASC. Importantly, Saos-2 cells were able to deposit calcium in the presence of WPI, even in a proliferation medium without other supplements that support osteogenic cell differentiation. The results indicate that, depending on the cell type, WPI can act as an enhancer of cell proliferation and osteogenic differentiation. Therefore, enrichment of biomaterials for bone regeneration with WPI seems a promising approach, especially due to the low cost of WPI.     

Gel mechanical properties of milk whey protein–dextran conjugates obtained by Maillard reaction

The effect of Maillard reaction on the mechanical properties of whey protein isolate (WPI) heat-induced gels was evaluated. WPI and dextran (15–25 kDa) conjugates were obtained by controlled dry heating during storage at 60 °C and 63% relative humidity for 2, 5 and 9 days. Changes in browning intensity and content of free amino groups were used to estimate the Maillard reaction. A decrease in free amino groups of WPI was observed when increasing polysaccharide concentration and reaction time. An increase in both a* and b* CIE Lab colour parameters indicated the development of a reddish-brown colour, typical of the Maillard reaction. Uniaxial compression and stress relaxation tests were performed to measure the mechanical properties of mixed and conjugate gels. Maillard reaction significantly modified the mechanical properties of WPI/DX gels, and even prevented fracture when conjugate gels were subjected to 80% deformation in uniaxial compression test.     

Highly efficient enzyme-functionalized porous zirconia microtubes for bacteria filtration

In contrast to polymer membranes, ceramic membranes offer considerable advantages for safe drinking water provision due to their excellent chemical, thermal, and mechanical endurance. In this study, porous ceramic microtubes made of yttria stabilized zirconia (YSZ) are presented, which are conditioned for bacteria filtration by immobilizing lysozyme as an antibacterial enzyme. In accordance with determined membrane pore sizes of the nonfunctionalized microtube of ≤200 nm, log reduction values (LRV) of nearly 3 (i.e., bacterial retention of 99.9%) were obtained for bacterial retention studies using gram-positive model bacterium Micrococcus luteus. Immobilization studies of lysozyme on the membrane surface reveal an up to six times higher lysozyme loading for the covalent immobilization route as compared to unspecific immobilization. Antibacterial activity of lysozyme-functionalized microtubes was assessed by qualitative agar plate test using Micrococcus luteus as substrate showing that both the unspecific and the covalent lysozyme immobilization enhance the microtubes' antibacterial properties. Quantification of the enzyme activity at flow conditions by photometric assays reveals that the enzyme activities of lysozyme-functionalized microtubes depend strongly on applied flow rates. Intracapillary feeding of bacteria solution and higher flow rates lead to reduced enzyme activities. In consideration of different applied flow rates in the range of 0.2-0.5 mL/min, the total lysozyme activity increases by a factor of 2 for the covalent immobilization route as compared to the unspecific binding. Lysozyme leaching experiments at flow conditions for 1 h show a significant higher amount of washed-out lysozyme (factor 1.7-3.4) for the unspecific immobilization route when compared to the covalent route where the initial level of antibacterial effectiveness could be achieved by reimmobilization with lysozyme. The presented platform is highly promising for sustainable bacteria filtration.     

Direct determination of polymerised triacylglycerides in deep-frying vegetable oil by near infrared spectroscopy using Partial Least Squares regression

A green method for the determination of polymerised triacylglyceride (PTG) in deep-frying vegetable oils of different botanic origin has been developed employing near infrared (NIR) spectroscopy and Partial Least Squares (PLS) regression. Four different types of oil were heated during several hours, with and without the addition of foodstuff. NIR transmission spectra were obtained directly from sample aliquots stored in glass vials, thus avoiding the consumption of solvents and minimising waste generation. Variables employed for building the PLS models were selected applying interval PLS (iPLS) as well as Uninformative Variable Elimination-PLS (UVE-PLS). A global PLS model using spectra of all four types of oils was compared to PLS models established for each oil type. Due to the small differences observed in the NIR spectra that can be related to the different botanic origin and results obtained from the PLS model comparison, the use of a global PLS model is recommended leading to prediction errors of 2.28% (w/w) for the determination of PTG in oils employed for frying different kinds of foods.     

Approaches to modeling train scheduling problems as job-shop problems with blocking constraints

The problem of scheduling a set of trains traveling through a given railway network consisting of single tracks, sidings and stations is considered. For every train a fixed route and travel times, an earliest departure time at the origin and a desired arrival time at the destination are given. A feasible schedule has to be determined which minimizes total tardiness of all trains at their destinations. This train scheduling problem is modeled as a job-shop scheduling problem with blocking constraints, where jobs represent trains and machines constitute tracks or track sections. Four MIP formulations without time-indexed variables are developed based on two different transformation approaches of parallel tracks and two different types of decision variables leading to job-shop scheduling problems with or without routing flexibility. A computational study is made on hard instances with up to 20 jobs and 11 machines to compare the MIP models in terms of total tardiness values, formulation size and computation time.     

Consumers' Creative Talent: Which Characteristics Qualify Consumers for Open Innovation Projects? An Exploration of Asymmetrical Effects

Virtual customer integration and open innovation are considered as appropriate means to improve the success of new product development. However, only when consumers are qualified and motivated to contribute promising ideas and relevant know‐how they are able to add value to a producer's innovation process. In this study, we explore the symmetric and asymmetric impact of various creativity components on consumers' idea generation, concept development, or prototype building abilities as well as interest in co‐creation projects. Our results show that creativity components are of different importance. While some characteristics are needed above certain thresholds to successfully accomplish a certain development task, exceeding those does not necessarily lead to better outputs. Other characteristics improve the creative output only if they exceed specific levels.     

Integrative Analysis of Metabolomic,Proteomic and Genomic Data to Reveal Functional Pathways and Candidate Genes for Drip Loss in Pigs

The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein “phosphoglycerate mutase 2” and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes.