The COVID-19 pandemic and its skin effects.

OBJECTIVE: To review the current literature on cutaneous diseases associated with the global coronavirus disease 2019 (COVID-19) pandemic, and to provide a general overview for family physicians of dermatologic presentations associated with COVID-19. QUALITY OF EVIDENCE: Google Scholar and PubMed searches were conducted using the terms COVID-19, SARS-CoV-2, pandemic, dermatology, livedoid, chilblain, urticaria, maculopapular, Kawasaki's, and related synonyms. Additional terms were personal protective equipment (PPE), hand hygiene, and psychosocial factors affecting skin diseases. Only English-language literature was reviewed. Evidence ranged from levels I to III. MAIN MESSAGE: Coronavirus disease 2019 is associated with a range of cutaneous presentations through direct infection with severe acute respiratory syndrome coronavirus 2, such as maculopapular, vesicular, pseudo-chilblain, livedoid, necrotic, urticarial, and Kawasaki-like rashes. Indirect presentations secondary to behavioural modifications are associated with use of personal protective equipment and sanitization procedures. Furthermore, psychosocial factors and stress associated with the pandemic also exacerbate pre-existing skin conditions. CONCLUSION: The COVID-19 pandemic has increased rates of dermatologic conditions through direct infection, behavioural changes, and association with psychosocial factors. As the incidence of COVID-19 increases, family physicians should be well equipped to diagnose and manage dermatologic presentations as they change within the context of the pandemic.

Structure and function of a lignostilbene-α,ß-dioxygenase orthologue from Pseudomonas brassicacearum.

BACKGROUND: Stilbene cleaving oxygenases (SCOs), also known as lignostilbene-α,ß-dioxygenases (LSDs) mediate the oxidative cleavage of the olefinic double bonds of lignin-derived intermediate phenolic stilbenes, yielding small modified benzaldehyde compounds. SCOs represent one branch of the larger carotenoid cleavage oxygenases family. Here, we describe the structural and functional characterization of an SCO-like enzyme from the soil-born, bio-control agent Pseudomonas brassicacearum. METHODS: In vitro and in vivo assays relying on visual inspection, spectrophotometric quantification, as well as liquid-chormatographic and mass spectrometric characterization were applied for functional evaluation of the enzyme. X-ray crystallographic analyses and in silico modeling were applied for structural investigations. RESULTS: In vitro assays demonstrated preferential cleavage of resveratrol, while in vivo analyses detected putative cleavage of the straight chain carotenoid, lycopene. A high-resolution structure containing the seven-bladed ß-propeller fold and conserved 4-His-Fe unit at the catalytic site, was obtained. Comparative structural alignments, as well as in silico modelling and docking, highlight potential molecular factors contributing to both the primary in vitro activity against resveratrol, as well as the putative subsidiary activities against carotenoids in vivo, for future validation. CONCLUSIONS: The findings reported here provide validation of the SCO structure, and highlight enigmatic points with respect to the potential effect of the enzyme's molecular environment on substrate specificities for future investigation.

Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate.

Kinesin-13 proteins are major microtubule (MT) regulatory factors that catalyze removal of tubulin subunits from MT ends. The class-specific "neck" and loop 2 regions of these motors are required for MT depolymerization, but their contributing roles are still unresolved because their interactions with MT ends have not been observed directly. Here we report the crystal structure of a catalytically active kinesin-13 monomer (Kif2A) in complex with two bent αß-tubulin heterodimers in a head-to-tail array, providing a view of these interactions. The neck of Kif2A binds to one tubulin dimer and the motor core to the other, guiding insertion of the KVD motif of loop 2 in between them. AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs. These results provide mechanistic insights into the catalytic cycles of kinesin-13.