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Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis. [ABSTRACT FROM AUTHOR]

Cleavage and religation half-reactions of topoisomerase I are not affected by PSF/p54(super.nrb) based on a recent study. The enzyme has a tendency to jump between different DNA helices, and this has been stimulated by PSF/p54(super.nrb). Stimulation of topoisomerase I catalysis by PSF/p54(super.nrb) is apparently affected by mobilization of the enzyme.

A study was conducted to examine the topoisomerase I-mediated coupling of H2O2 to the cleaved DNA strand at neutral pH. Results indicated that the the coupling of H2O2 was inhibited by camptothecins. A DNA synthesizer was utilized to determine oligonucleotides for topoisomerase I suicide substrates. Findings also showed that the presence of DNA 3' to the cleavage site did not support camptothecin actions.

The interaction of dexnigulpidine hydrochloride with the function of purified recombinant human DNA topoisomerase was investigated through immuno-dot-blotting of DNA-linked topoisomerase I. Results have shown that dihydropyridine dexniguldipine hydrochloride inhibited both the DNA cleavage and religation reactions catalyzed by DNA topoisomerase I. The inhibition was secondary to the suppressed noncovalent binding of the enzyme to the DNA or to the decrease in the DNA cleavage reaction itself.

Analysis of the properties of synthesized derivatives of the fluorescent beta-adrenoceptor ligand CGP 12177 revealed that the BODIPY-CGP derivative-generated receptor-specific signal is strong enough for use in computing rate and equilibrium dissociation constants for beta-adrenoceptor specific binding. The thermodynamics of beta(2)-adrenoceptors in BODIPY-CGP-stained Sf9 cells reveals the validity of BODIPY-CGP use for staining beta-adrenoceptor-expressing cells.

Aims: Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β1‐adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine‐map the conformational epitope within the second extracellular loop of the human β1‐adrenoceptor (β1ECII) that is targeted by stimulating β1‐receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto‐epitope. Methods and results: Non‐conserved amino acids within the β1ECII loop (compared with the amino acids constituting the ECII loop of the β2‐adrenoceptor) were one by one replaced with alanine; potential intra‐loop disulfide bridges were probed by cysteine–serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking β1ECII ± the above replacements, and (ii) by (auto)antibody stimulation of human β1‐adrenoceptors bearing corresponding point mutations. With the use of stimulating β1‐receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the β1ECII loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK211–214 motif and (ii) the intra‐loop disulfide bond C209↔C215. Of note, aberrant intra‐loop disulfide bond C209↔C216 almost fully disrupted the functional auto‐epitope in cyclopeptides. Conclusions: The conformational auto‐epitope targeted by cardio‐pathogenic β1‐receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β1ECII loop bearing the NDPK211–214 motif and the C209↔C215 bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β1‐autoantibody‐positive CHF. [ABSTRACT FROM AUTHOR]