Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.     

Abnormal Pre-mRNA Splicing in Exonic Fabry Disease-Causing GLA Mutations

Fabry disease (FD) is a rare X-linked disease due to a multiverse of disrupting mutations within the GLA gene encoding lysosomal α-galactosidase A (AGAL). Absent AGAL activity causes the accumulation of complex glycosphingolipids inside of lysosomes in a variety of cell types and results in a progressive multisystem disease. Known disease-associated point mutations in protein-coding gene regions usually cause translational perturbations and result in premature chain termination, punctual amino acid sequence alterations or overall altered sequence alterations downstream of the mutation site. However, nucleotide exchanges at the border between introns and exons can affect splicing behavior and lead to abnormal pre-mRNA processing. Prediction with the Human Splicing Finder (HSF) revealed an indication of a significant change in splicing-relevant information for some known FD-associated GLA mutations. To experimentally determine the extent of the change, we made use of a minigene reporter assay and verified alternative splicing events for the exonic mutations c.194G>T and c.358C>G, which led to the usage of alternative donor splice sites at exon 1 and exon 2, respectively. In addition, the mutations c.548G>T and c.638A>T led to significant exon 4 skipping. We conclude that splicing phenotype analysis should be employed in the in vitro analysis of exonic GLA gene mutations, since abnormal splicing may result in a reduction of enzyme activity and alter the amenability for treatment with pharmacological chaperone (PC).     

Moving Fourier Analysis for Locally Stationary Processes with the Bootstrap in View

We introduce a moving Fourier transformation for locally stationary time series, which captures the time‐varying spectral density in a similar manner as the classical Fourier transform does for stationary time series. In particular, the resulting Fourier coefficients as well as moving local periodograms are shown to be (almost all) asymptotically uncorrelated. The moving local periodogram is obtained by thinning the local periodogram to avoid multiple information present at different but close points in time. We obtain consistent estimators for the local spectral density at each point in time by smoothing the moving local periodogram. Furthermore, the moving Fourier coefficients, respectively periodograms, are well suited to adapt stationary frequency domain bootstrap methods to the locally stationary case. For the wild time frequency toggle bootstrap, it is shown that the corresponding bootstrap covariance of a global locally stationary bootstrap samples captures the time‐varying covariance structure of the underlying locally stationary time series correctly. Furthermore, this bootstrap in addition to adaptations of other frequency domain bootstrap methods is used in a simulation study to obtain uniform confidence bands for the time‐varying autocorrelation at lag 1. Finally, this methodology is applied to a wind data set.     

Neuartige Goldkatalysatoren auf Alumophosphat‐Basis für die direkte Propen‐Epoxidierung

Propene oxide is an important intermediate in chemical industry. Amongst others it is needed for the production of various plastics. As currently applied processes for the production of propene oxide either generate large amounts of undesired by‐products or are highly expensive regarding the reactants introduced to the process, it is desirable to epoxidate propene directly by aerial oxygen. It has been shown that this is possible by the use of supported gold catalysts. This contribution engages in the question to which extent titanium substituted alumophosphates are suitable as support for this kind of catalysts.     

Two tetraplex real-time PCR for the detection and quantification of DNA from eight allergens in food

According to the EU and Swiss legislation, food has to be labelled for allergens to enable allergic consumers to avoid such food and its products. To provide efficient and reliable methods, two novel quantitative multiplex real-time polymerase chain reaction systems were developed and validated. They simultaneously determine DNA of peanut, hazelnut, celery, soy, egg, milk, almond and sesame, respectively. The tests exhibit good specificity and sensitivity in the range of 0.01%. Due to low DNA amounts, lower sensitivities for egg and milk were obtained. First comparisons of ELISA results with PCR results suggest a qualitative accordance, but a low correlation of quantitative results.     

Caffeoylquinic acid derived free radicals identified during antioxidant reactions of bitter tea (Ilex latifolia and Ilex kudincha)

In order to provide some insight into the chemical basis for the antioxidant behaviour of bitter tea, the Chinese medicinal beverage derived from leaves of Ilex kudincha or Ilex latifolia, free radicals generated during the oxidation of aqueous extracts of dried leaves have been investigated by electron paramagnetic resonance (EPR) spectroscopy. With both beverages, the major components in the EPR spectra after accelerated autoxidation under alkaline conditions or oxidation with the superoxide anion radical were comparable to those derived from reactions of caffeoylquinic acids. Thus these reaction products have sufficient stability for biological activity, and the present results suggest that such molecules contribute appreciably to the antioxidant chemistry of these beverages.     

Identifying the unknowns by aligning fragmentation trees

Mass spectrometry allows sensitive, automated, and high-throughput analysis of small molecules. In principle, tandem mass spectrometry allows us to identify "unknown" small molecules not in any database, but the automated interpretation of such data is in its infancy. Fragmentation trees have recently been introduced for the automated analysis of the fragmentation patterns of small molecules. We present a method for the automated comparison of such fragmentation patterns, based on aligning the compounds' fragmentation trees. We cluster compounds based solely on their fragmentation patterns and show a good agreement with known compound classes. Fragmentation pattern similarities are strongly correlated with the chemical similarity of molecules. We present a tool for searching a database for compounds with fragmentation pattern similar to an unknown sample compound. We apply this tool to metabolites from Icelandic poppy. Our method allows fully automated computational identification of small molecules that cannot be found in any database.     

Investigation of the Photocatalytic Hydrogen Production of Semiconductor Nanocrystal-Based Hydrogels

Destabilization of a ligand-stabilized semiconductor nanocrystal solution with an oxidizing agent can lead to a macroscopic highly porous self-supporting nanocrystal network entitled hydrogel, with good accessibility to the surface. The previously reported charge carrier delocalization beyond a single nanocrystal building block in such gels can extend the charge carrier mobility and make a photocatalytic reaction more probable. The synthesis of ligand-stabilized nanocrystals with specific physicochemical properties is possible, thanks to the advances in colloid chemistry made in the last decades. Combining the properties of these nanocrystals with the advantages of nanocrystal-based hydrogels will lead to novel materials with optimized photocatalytic properties. This work demonstrates that CdSe quantum dots, CdS nanorods, and CdSe/CdS dot-in-rod-shaped nanorods as nanocrystal-based hydrogels can exhibit a much higher hydrogen production rate compared to their ligand-stabilized nanocrystal solutions. The gel synthesis through controlled destabilization by ligand oxidation preserves the high surface-to-volume ratio, ensures the accessible surface area even in hole-trapping solutions and facilitates photocatalytic hydrogen production without a co-catalyst. Especially with such self-supporting networks of nanocrystals, the problem of colloidal (in)stability in photocatalysis is circumvented. X-ray photoelectron spectroscopy and photoelectrochemical measurements reveal the advantageous properties of the 3D networks for application in photocatalytic hydrogen production.     

Communicating Particles: Identification Taggant and Temperature Recorder in One Single Supraparticle

“Communicating particles” are reported that combine an identification (ID) taggant and a temperature recorder in one single entity—a micron-scaled supraparticle. The optical information carriers within the hybrid inorganic-organic supraparticles are three different types of luminescent nanoparticles, which can be read-out using single-wavelength excitation. These three nanoparticle types are assembled into a core-satellite structure via a two-step droplet evaporation technique. The core is built-up from Tb³⁺ and Eu³⁺-doped nanophosphors, providing an environmentally stable ID that is easily tunable through ratiometric spectral coding. This core is surrounded by organic, dye-doped polymer nanoparticle satellites, acting as thermal-history-recorders of their environment. Exposed to a threshold temperature, the luminescence of the utilized 7-diethylamino-4-methylcoumarin-doped polymer nanoparticles is irreversibly quenched. This “turn-off ” signal response is attributed to conformational changes in the dyes’ excited state and an alteration of their molecular environment, respectively, triggered by the polymer nanoparticles’ glass transition. Thus, the sensitivity of the temperature recorder can be configured over a wide temperature range by varying the dye-hosting polymer. At the same time, the ID of the particle, stemming from its inorganic building blocks, stays unaffected, thus stable against thermal changes. The idea of communicating particles introduces a promising concept for smart additives.     

Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents, AKI can be effectively prevented through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans), longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, particularly arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.