Optimization of plasma-based BioID identifies plasminogen as a ligand of ADAMTS13.

ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13, regulates the length of Von Willebrand factor (VWF) multimers and their platelet-binding activity. ADAMTS13 is constitutively secreted as an active protease and is not inhibited by circulating protease inhibitors. Therefore, the mechanisms that regulate ADAMTS13 protease activity are unknown. We performed an unbiased proteomics screen to identify ligands of ADAMTS13 by optimizing the application of BioID to plasma. Plasma BioID identified 5 plasma proteins significantly labeled by the ADAMTS13-birA* fusion, including VWF and plasminogen. Glu-plasminogen, Lys-plasminogen, mini-plasminogen, and apo(a) bound ADAMTS13 with high affinity, whereas micro-plasminogen did not. None of the plasminogen variants or apo(a) bound to a C-terminal truncation variant of ADAMTS13 (MDTCS). The binding of plasminogen to ADAMTS13 was attenuated by tranexamic acid or ε-aminocaproic acid, and tranexamic acid protected ADAMTS13 from plasmin degradation. These data demonstrate that plasminogen is an important ligand of ADAMTS13 in plasma by binding to the C-terminus of ADAMTS13. Plasmin proteolytically degrades ADAMTS13 in a lysine-dependent manner, which may contribute to its regulation. Adapting BioID to identify protein-interaction networks in plasma provides a powerful new tool to study protease regulation in the cardiovascular system.

Determinants of Learning Anatomy in an Immersive Virtual Reality Environment - A Scoping Review.

Given the decline of cadavers as anatomy teaching tools, immersive virtual reality (VR) technology has gained popularity as a potential alternative. To better understand how to maximize the educational potential of VR, this scoping review aimed to identify potential determinants of learning anatomy in an immersive VR environment. A literature search yielded 4523 studies, 25 of which were included after screening. Six common factors were derived from secondary outcomes in these papers: cognitive load, cybersickness, student perceptions, stereopsis, spatial understanding, and interactivity. Further objective research investigating the impact of these factors on anatomy examination performance is required. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01701-y.

Size matters! Investigating the effects of model size on anatomy learning.

Three-dimensional (3D) scanning and printing technology has allowed for the production of anatomical replicas at virtually any size. But what size optimizes the educational potential of 3D printing models? This study systematically investigates the effect of model size on nominal anatomy learning. The study population of 380 undergraduate students, without prior anatomical knowledge, were randomized to learn from two of four bone models (either vertebra and pelvic bone [os coxae], or scapula and sphenoid bone), each model 3D printed at 50%, 100%, 200%, and either 300% or 400% of normal size. Participants were then tested on nominal anatomy recall on the respective bone specimens. Mental rotation ability and working memory were also assessed, and opinions regarding learning with the various models were solicited. The diameter of the rotational bounding sphere for the object ("longest diameter") had a small, but significant effect on test score (F(2,707) = 17.15, p < 0.05, R2  = 0.046). Participants who studied from models with a longest diameter greater than 10 cm scored significantly better than those who used models less than 10 cm, with the exception of the scapula model, on which performance was equivalent across all sizes. These results suggest that models with a longest diameter beyond 10 cm are unlikely to incur a greater size-related benefit in learning nominal anatomy. Qualitative feedback suggests that there also appear to be inherent features of bones besides longest diameter that facilitate learning.

Mechanisms of ADAMTS13 regulation.

Recombinant ADAMTS13 is currently undergoing clinical trials as a treatment for hereditary thrombotic thrombocytopenic purpura, a lethal microvascular condition resulting from ADAMTS13 deficiency. Preclinical studies have also demonstrated its efficacy in treating arterial thrombosis and inflammation without causing bleeding, suggesting that recombinant ADAMTS13 may have broad applicability as an antithrombotic agent. Despite this progress, we currently do not understand the mechanisms that regulate ADAMTS13 activity in vivo. ADAMTS13 evades canonical means of protease regulation because it is secreted as an active enzyme and has a long half-life in circulation, suggesting that it is not inhibited by natural protease inhibitors. Although shear can spatially and temporally activate von Willebrand factor to capture circulating platelets, it is also required for cleavage by ADAMTS13. Therefore, spatial and temporal regulation of ADAMTS13 activity may be required to stabilize von Willebrand factor-platelet strings at sites of vascular injury. This review outlines potential mechanisms that regulate ADAMTS13 in vivo including shear-dependency, local inactivation, and biochemical and structural regulation of substrate binding. Recently published structural data of ADAMTS13 is discussed, which may help to generate novel hypotheses for future research.