Evolutionary adaptations of doublet microtubules in trypanosomatid parasites.

The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo-electron microscopy structures of DMTs from two trypanosomatid species, and , at resolutions up to 2.7 angstrom.

The hypertrophic cardiomyopathy-associated A331P actin variant enhances basal contractile activity and elicits resting muscle dysfunction.

Previous studies aimed at defining the mechanistic basis of hypertrophic cardiomyopathy caused by A331P cardiac actin have reported conflicting results. The mutation is located along an actin surface strand, proximal to residues that interact with tropomyosin. These F-actin-tropomyosin associations are vital for proper contractile inhibition.

Osteoid osteoma: A masquerader of persistent knee pain in the setting of prior lateral tibial plateau cement subchondroplasty.

Osteoid Osteoma (OO) is a common primary bone tumor that often presents with night pain in younger orthopedic patients. Although typically extra-articular, intra-articular presentations may be difficult to diagnose. While magnetic resonance imaging (MRI) provides excellent detailed imaging of the articular surface, it has been reported to lead to occasional misdiagnosis given limitations in spatial resolution, particularly for smaller lesions.

AAV-mediated co-expression of an immunogenic transgene plus PD-L1 enables sustained expression through immunological evasion.

Adeno-associated virus (AAV) vectors can mediate long-term expression of immunogenic transgenes in vivo through transduction of tolerogenic cells in the liver. Tissue-targeted AAV vectors allow transduction of non-hepatic cells, but this necessitates development of strategies to minimize transgene immunogenicity. Here, we first validated that AAV capsids with tissue-specific tropism and transgene promoters enabled expression of the immunogenic protein, firefly luciferase, in liver, muscle, or adipose tissue.