The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis.

Inhibition of integrin αvβ6 is a promising approach to the treatment of fibrotic disease such as idiopathic pulmonary fibrosis. Screening a small library combining head groups that stabilize the bent-closed conformation of integrin αIIbβ3 with αv integrin binding motifs resulted in the identification of hit compounds that bind the bent-closed conformation of αvβ6. Crystal structures of these compounds bound to αvβ6 and related integrins revealed opportunities to increase potency and selectivity, and these efforts were accelerated using accurate free energy perturbation (FEP+) calculations.

The Influence of SARS-CoV-2 Vaccination on the Mortality and Outcomes of Patients with Both Myocardial Infarction and COVID-19.

This multi-site retrospective analysis with a control group was devised to evaluate the impact of prophylactic SARS-CoV-2 vaccination the on outcomes of myocardial infarction (MI) patients with confirmed COVID-19. An overall of 129 subjects who had been diagnosed with COVID-19 and MI were included in the analysis and were divided into the study group (44 vaccinated patients) and the control group (85 non-vaccinated comparable patients). The primary outcome measure was defined as the time until in-hospital death, while the secondary outcome measure was defined as the time until death outside the hospital setting.

Chameleon Sequences-Structural Effects in Proteins Characterized by Hydrophobicity Disorder.

Repeated protein folding processes both in vivo and in vitro leading to the same structure for a specific amino acid sequence prove that the amino acid sequence determines protein structuring. This is also evidenced by the variability of structuring, dependent on the introduced mutations. An important phenomenon in this regard is the presence of a differentiated secondary structure for chain fragments of identical sequence representing distinct forms of the secondary-order structure.

Beyond embodiment: Rethinking the integration of cognitive neuroscience and mechanistic explanations.

This commentary critiques Mougenot and Matheson's proposal to integrate embodied cognition with mechanistic explanations in cognitive neuroscience. We suggest more promising directions for embodied cognitive neuroscience, focusing on neuroethological research and evolutionary studies of nervous systems. These approaches, compatible with wide mechanistic explanations, offer a robust path forward by examining central nervous system function within whole organisms in their environments.