Body burdens of persistent halogenated compounds during different development stages of anadromous brown trout (Salmo trutta)

Polychlorinated biphenyls (PCBs), DDTs, and polybrominated diphenyl ethers (PBDEs) were followed through the five life stages of a wild population of anadromous brown trout and related to variations in lipid content and exposure situations. Anadromous brown trout exhibits great variations in lipid content during its life cycle in the freshwater and marine environments. The results indicated substantial differences in PBDE and organochlorine exposure, with apparently more recent sources of PBDEs in the freshwater environment relative to the marine environment. Lipid and contaminant transfer were not always identical: The concentrations of PCBs, DDTs, and PBDEs (ng/g lipid weight) were about 15 times lower in the eggs compared to the muscle of their mother (e.g., 823 ng PCB/g Iw vs. 12,565 ng PCB/g lw, respectively). During the starving period from maiden to spawning trout the contaminant load increased by a higher factor than the lipid use. The data suggest a decoupling between lipid content and organohalogen concentrations for anadromous brown trout, which may contribute positively to reduce any potential negative effects of the transferred contaminants on eggs and fry.     

Unique Glycoform-Dependent Monoclonal Antibodies for Mouse Mucin 21

Mucin 21(Muc21)/epiglycanin is expressed on apical surfaces of squamous epithelia and has potentially protective roles, which are thought to be associated with its unique glycoforms, whereas its aberrant glycosylation is implicated in the malignant behaviors of some carcinomas. Despite the importance of glycoforms, we lack tools to detect specific glycoforms of mouse Muc21. In this study, we generated two monoclonal antibodies (mAbs) that recognize different glycoforms of Muc21. We used membrane lysates of Muc21-expressing TA3-Ha cells or Chinese hamster ovary (CHO)-K1 cells transfected with Muc21 as antigens. Specificity testing, utilizing Muc21 glycosylation variant cells, showed that mAb 1A4-1 recognized Muc21 carrying glycans terminated with galactose residues, whereas mAb 18A11 recognized Muc21 carrying sialylated glycans. mAb 1A4-1 stained a majority of mouse mammary carcinoma TA3-Ha cells in vitro and in engrafted tumors in mice, whereas mAb 18A11 recognized only a subpopulation of these. mAb 1A4-1 was useful in immunohistochemically detecting Muc21 in normal squamous epithelia. In conclusion, these mAbs recognize distinct Muc21 epitopes formed by combinations of peptide portions and O-glycans.     

Ermüdungsprobleme dünnwandiger kaltgeformter Bauteile

Fatigue behaviour of thin‐walled coldformed steel profiles. Current design concepts for thin‐walled structural members take local buckling into account in determining the ultimate capacity. Local buckling may be accompanied by large deformations, which entail secondary bending stresses. Such secondary stresses can be neglected in usual design, but there are no information available regarding their influence on fatigue design. For the investigation of that problem fatigue tests were carried out with thin‐walled cold‐formed U‐channels exposed to pure bending. Following the systematically numerical investigations it will be proposed to limit the cyclic load by 60% of the ultimate load in order to avoid fatigue damage of thin‐walled cold‐formed profiles.     

Practical TEMPO‐Mediated Oxidation of Alcohols using Different Polymer‐Bound Co‐Oxidants

Hypochlorite and chlorite exchange resins are evaluated as co‐oxidants or oxidants, respectively, for the oxidation of alcohols to the corresponding aldehydes, ketones or carboxylic acids. Polymer‐bound hypochlorite can act as a co‐oxidant in TEMPO‐mediated oxidations of alcohols. The formation of aldehydes only works under weakly acidic conditions. However, the cheap hypochlorite exchange resin is less efficient as co‐oxidant compared to the use of ionically immobilised bisacetoxybromate(I) anions. In contrast, the chlorite exchange resin is a highly potent co‐oxidant for the preparation of carboxylic acids from the corresponding primary alcohols in the presence of TEMPO. It is demonstrated that in this case also the resin acts as a polymer‐bound co‐oxidant for both oxidation steps. Yields are commonly excellent as is also demonstrated for examples taken from natural product synthesis which include acid labile glycosides. In most cases, work‐up of this heavy metal‐free oxidation is kept to a minimum. It often includes filtration followed by removal of the solvent.     

Identification of SCN5a p.C335R Variant in a Large Family with Dilated Cardiomyopathy and Conduction Disease

Introduction: Familial dilated cardiomyopathy (DCM) is clinically variable and has been associated with mutations in more than 50 genes. Rapid improvements in DNA sequencing have led to the identification of diverse rare variants with unknown significance (VUS), which underlines the importance of functional analyses. In this study, by investigating human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we evaluated the pathogenicity of the p.C335R sodium voltage-gated channel alpha subunit 5 (SCN5a) variant in a large family with familial DCM and conduction disease. Methods: A four-generation family with autosomal dominant familial DCM was investigated. Next-generation sequencing (NGS) was performed in all 16 family members. Clinical deep phenotyping, including endomyocardial biopsy, was performed. Skin biopsies from two patients and one healthy family member were used to generate human-induced pluripotent stem cells (iPSCs), which were then differentiated into cardiomyocytes. Patch-clamp analysis with Xenopus oocytes and iPSC-CMs were performed. Results: A SCN5a variant (c.1003T>C; p.C335R) could be detected in all family members with DCM or conduction disease. A novel truncating TTN variant (p.Ser24998LysfsTer28) could also be identified in two family members with DCM. Family members with the SCN5a variant (p.C335R) showed significantly longer PQ and QRS intervals and lower left ventricular ejection fractions (LV-EF). All four patients who received CRT-D were non-responders. Electrophysiological analysis with Xenopus oocytes showed a loss of function in SCN5a p.C335R. Na⁺ channel currents were also reduced in iPSC-CMs from DCM patients. Furthermore, iPSC-CM with compound heterozygosity (SCN5a p.C335R and TTNtv) showed significant dysregulation of sarcomere structures, which may be contributed to the severity of the disease and earlier onset of DCM. Conclusion: The SCN5a p.C335R variant is causing a loss of function of peak INa in patients with DCM and cardiac conduction disease. The co-existence of genetic variants in channels and structural genes (e.g., SCN5a p.C335R and TTNtv) increases the severity of the DCM phenotype.     

Agent-based simulations for protecting nursing homes with prevention and vaccination strategies

Due to its high lethality among older people, the safety of nursing homes has been of central importance during the COVID-19 pandemic. With test procedures and vaccines becoming available at scale, nursing homes might relax prohibitory measures while controlling the spread of infections. By control we mean that each index case infects less than one other person on average. Here, we develop an agent-based epidemiological model for the spread of SARS-CoV-2 calibrated to Austrian nursing homes to identify optimal prevention strategies. We find that the effectiveness of mitigation testing depends critically on test turnover time (time until test result), the detection threshold of tests and mitigation testing frequencies. Under realistic conditions and in absence of vaccinations, we find that mitigation testing of employees only might be sufficient to control outbreaks if tests have low turnover times and detection thresholds. If vaccines that are 60% effective against high viral load and transmission are available, control is achieved if 80% or more of the residents are vaccinated, even without mitigation testing and if residents are allowed to have visitors. Since these results strongly depend on vaccine efficacy against infection, retention of testing infrastructures, regular testing and sequencing of virus genomes is advised to enable early identification of new variants of concern.     

GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression

Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in P. gingivalis-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in GDF15 siRNA-treated HPdLF stimulated with P. gingivalis lipopolysaccharides alone and in combination with compressive force. GDF15 knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions.     

Tyrosinase-glucose dehydrogenase substrate-recycling biosensor: A highly-sensitive measurement of phenolic compounds

Mushroom tyrosinase and glucose dehydrogenase from Acinetobacter calcoaceticus were immobilized in poly(vinyl)alcohol membranes and coupled with a Clark-type oxygen electrode to give a substrate (analyte) regenerating cycle for monitoring of nanomolar concentrations of phenolic compounds. In this way the response for catechol, phenol, p-cresol, p-chlorophenol and p-acetamidophenol was amplified by a factor of 450, 300, 240, 150, and 140, respectively. The resulting detection limit for catechol and phenol is 0·6 nmol dm⁻³ and 0·9 nmol dm⁻³, respectively. The measuring linear range for phenol obtained by the amplified electrode extends from 1 to 400 nmol dm⁻³. The comparison with the chemical (ascorbic acid) regeneration of the phenolic compounds demonstrates the efficiency of the enzymatic procedure. The biosensor can be used for monitoring of phenolic compounds in environmental or industrial samples.