Examination of Cutaneous Changes Among Patients Following SARS-CoV-2 Infection.

Individuals infected with SARS-CoV-2 have been found to develop a variety of cutaneous symptoms. This study sought to describe varying cutaneous manifestations of COVID-19 in individuals presenting to an inpatient healthcare facility. We screened individuals who presented with COVID-19 for skin changes throughout the illness and administered a survey regarding demographics, medical history, and their cutaneous findings. Three individuals reported varying skin findings including wheals, petechiae, ecchymosis, and papules. One individual reported a worsening skin condition, psoriasis, as well as a new skin condition, seborrheic dermatitis. In conclusion, cutaneous manifestations of patients suffering from COVID-19 are wide-ranging and worsening skin conditions amongst these patients should be further investigated.

Controlling and exploiting intrinsic unpaired electrons in metalloproteins.

Electron paramagnetic resonance spectroscopy encompasses a versatile set of techniques that allow detailed insight into intrinsically occurring paramagnetic centers in metalloproteins and enzymes that undergo oxidation-reduction reactions. In this chapter, we discuss the process from isolating the protein to acquiring and analyzing pulse EPR spectra, adopting a practical perspective. We start with considerations when preparing the protein sample, explain techniques and procedures available for determining the reduction potential of the redox-active center of interest and provide details on methodologies to trap a given paramagnetic state for detailed pulse EPR studies, with an emphasis on biochemical and spectroscopic tools available when multiple EPR-active species are present. We elaborate on some of the most commonly used pulse EPR techniques and the choices the user has to make, considering advantages and disadvantages and how to avoid pitfalls. Examples are provided throughout.

A Longstanding, Persistent and Recurrent Case of Cryptogenic Panniculitis.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma. There may be a significant histologic overlap with traumatic panniculitis and lupus profundus. We describe a 54-year-old woman who had received a diagnosis of SPTCL based upon a left parietal scalp biopsy 5 years earlier. This diagnosis was supported by immunohistochemistry (IHC) demonstrating a CD8+ predominant lymphocyte population in the subcutis. T-cell gene rearrangement studies were not performed at that time. The patient was treated and showed significant clinical improvement. When several tender erythematous subcutaneous nodules appeared on the upper back, left plantar surface and pretibial region, repeat biopsy was performed. Histology revealed a lobular and septal panniculitis with no vasculitis. The infiltrate contained abundant eosinophils and histiocytes not seen in the original biopsy specimen. IHC demonstrated a mixture of CD4+, CD8+ and CD7+ lymphocytes with abundant CD68+ histiocytes. T-cell gene rearrangement studies performed on one of the lesions failed to demonstrate clonality. It is important to recognize that patients with SPTCL are not exempt from other types of panniculitis, and complete histologic, IHC and molecular workups are essential to properly classify all cutaneous lesions in these patients.

Characterisation of utrophin modulator SMT C1100 as a non-competitive inhibitor of firefly luciferase.

Firefly luciferase (FLuc) is a powerful tool for molecular and cellular biology, and popular in high-throughput screening and drug discovery. However, FLuc assays have been plagued with positive and negative artefacts due to stabilisation and inhibition by small molecules from a range of chemical classes. Here we disclose Phase II clinical compound SMT C1100 for the treatment of Duchenne muscular dystrophy as an FLuc inhibitor (KD of 0.40 ±â€¯0.15 µM). Enzyme kinetic studies using SMT C1100 and other non-competitive inhibitors including resveratrol and NFκBAI4 identified previously undescribed modes of inhibition with respect to FLuc's luciferyl adenylate intermediate. Employing a photoaffinity strategy to identify SMT C1100's binding site, a photolabelled SMT C1100 probe instead underwent FLuc-dependent photooxidation. Our findings support novel binding sites on FLuc for non-competitive inhibitors.

Electrocatalytic Volleyball: Rapid Nanoconfined Nicotinamide Cycling for Organic Synthesis in Electrode Pores.

In living cells, redox chains rely on nanoconfinement using tiny enclosures, such as the mitochondrial matrix or chloroplast stroma, to concentrate enzymes and limit distances that nicotinamide cofactors and other metabolites must diffuse. In a chemical analogue exploiting this principle, nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ are cycled rapidly between ferredoxin-NADP+ reductase and a second enzyme-the pairs being juxtaposed within the 5-100 nm scale pores of an indium tin oxide electrode. The resulting electrode material, denoted (FNR+E2)@ITO/support, can drive and exploit a potentially large number of enzyme-catalysed reactions.