Adaptive Evolution of Peptide Inhibitors for Mutating SARS-CoV-2.

The SARS-CoV-2 virus is currently causing a worldwide pandemic with dramatic societal consequences for the humankind. In the past decades, disease outbreaks due to such zoonotic pathogens have appeared with an accelerated rate, which calls for an urgent development of adaptive (smart) therapeutics. Here, a computational strategy is developed to adaptively evolve peptides that could selectively inhibit mutating S protein receptor binding domains (RBDs) of different SARS-CoV-2 viral strains from binding to their human host receptor, angiotensin-converting enzyme 2 (ACE2).

Activated Mesenchymal Stem Cells Induce Recovery Following Stroke Via Regulation of Inflammation and Oligodendrogenesis.

Background Brain repair mechanisms fail to promote recovery after stroke, and approaches to induce brain regeneration are scarce. Mesenchymal stem cells (MSC) are thought to be a promising therapeutic option. However, their efficacy is not fully elucidated, and the mechanism underlying their effect is not known.

Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1.

Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls.

Sample collection and amino acids analysis of extracellular fluid of mouse brain slices with low flow push-pull perfusion.

Brain tissue slices are a common neuroscience model that allows relatively sophisticated analysis of neuronal networks in a simplified preparation. Most experimental methodology utilizes electrophysiological tools to probe these model systems. The work here demonstrates the adaptation of low-flow push-pull perfusion sampling (LFPS) to a brain slice system.

Cytoplasmic delivery and selective, multicomponent labeling with oligoarginine-linked protein tags.

Strategies that leverage bio-orthogonal interactions between small molecule ligands and genetically encoded amino acid sequences can be used to attach high-performance fluorophores to proteins in living cells. However, a major limitation of chemical protein labeling is that cells' plasma membranes are impermeable to many useful probes and biolabels. Here, we show that conjugation to nonaarginine, a cell penetrating peptide (CPP), enables passive cytoplasmic delivery of otherwise membrane-impermeant, small molecule protein labels.

A non-antibacterial oxazolidinone derivative that inhibits epithelial cell sheet migration.

We have developed a high-throughput assay for screening chemical libraries for compounds that affect cell sheet migration during wound closure in epithelial cell monolayers. By using this assay, we have discovered a new inhibitor of cell sheet migration. This compound (UIC-1005) is a 3,4-disubstituted oxazolidinone that bears an electrophilic alpha,beta-unsaturated N-acyl group required for activity.