Combination of Autodisplay and Dynamic Pharmacophore Modeling Reveals New Insights into Cyclic Nucleotide Binding in Hyperpolarization-Activated and Cyclic Nucleotide-Gated Ion Channel 4 (HCN4).

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play a critical role in regulating neuronal and cardiac rhythmicity, with their function being modulated by cyclic nucleotide binding. Dysfunction of HCN ion channels leads to the genesis of several diseases such as arrhythmia, bradycardia, or epilepsy. This study employs a multidisciplinary approach integrating mutagenesis, ligand binding assays, and molecular dynamics (MD) simulations combined with dynamic pharmacophore studies to investigate the impact of single residue mutations within the cyclic nucleotide-binding domain (CNBD) of HCN4 channels.

Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.

Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases.

Cytoplasmic short linear motifs in ACE2 and integrin β link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy.

The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the host cell surface and subsequently enters host cells through receptor-mediated endocytosis. Additional cell receptors may be directly or indirectly involved, including integrins. The cytoplasmic tails of ACE2 and integrins contain several predicted short linear motifs (SLiMs) that may facilitate internalization of the virus as well as its subsequent propagation through processes such as autophagy.

Monoclonal anti-CD20 Antibody Therapy in Cicatrical Pemphigoid with Oral and Hypopharyngeal Involvement and Related Conditions.

Mucous membrane pemphigoid is a rare blistering autoimmune disorder that can lead to significant disability. Recently, the monoclonal anti-CD20 antibody rituximab has shown efficacy in pemphigus and pemphigoid, but the data for pemphigoid are relatively sparse. The authors report a series of four patients with severe cicatrical pemphigoid treated with rituximab.

Determination of total iron in food samples after flow injection preconcentration on polyurethane foam functionalized with N,N-bis(salicylidene)-1,3-propanediamine.

A highly selective flow injection sorption system was developed for the fast determination of total iron in food samples. Iron (III) was reduced to iron (II) by ascorbic acid and preconcentrated on a mini-column packed with polyurethane foam (PUF) functionalized with N,N-bis(salicylidene)-1,3-propanediamine (SPDA). The retained Fe (II) was eluted with hydrochloric acid and subsequently reacted to 2,4,6-tri(2'-pyridyl)-1,3,5-triazine (TPTZ) then measured at 593 nm.