Protein sequence evolution in the presence of epistasis makes many previously acceptable amino acid residues at a site unfavorable over time. This phenomenon of entrenchment has also been observed with neutral substitutions using Potts Hamiltonian models. Here, we show that simulations using these models often evolve non-neutral proteins.
View Article and Find Full Text PDFBr J Hosp Med (Lond)
December 2024
Sjögren disease (SjD) is a systemic autoimmune disorder affecting both children and adults, with a wide range of clinical phenotypes. It remains a challenging condition to recognise and diagnose early and manage effectively. The heterogeneous nature of the presentation, variable disease course and overlapping symptoms with other autoimmune conditions often result in delayed diagnosis.
View Article and Find Full Text PDFAdeno-associated viruses (AAVs) have emerged as a promising gene delivery vehicle for the treatment of diseases. As AAVs are a complex therapeutic modality, new analytical techniques are needed to thoroughly characterize the critical quality attributes (CQAs) to support drug development. Empty and full ratio is one of the CQAs of AAVs that may impact drug safety and efficacy.
View Article and Find Full Text PDFScaffolds made from cartilage extracellular matrix are promising materials for articular cartilage repair, attributed to their intrinsic bioactivity that may promote chondrogenesis. While several cartilage matrix-based scaffolds have supported chondrogenesis and/or , it remains a challenge to balance the biological response (e.g.
View Article and Find Full Text PDFPosition Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on an analysis of the literature regarding the effects of β-Hydroxy-β-Methylbutyrate (HMB). The following 12 points have been approved by the Research Committee of the Society: 1. HMB is a metabolite of the amino acid leucine that is naturally produced in both humans and other animals.
View Article and Find Full Text PDF