Evolutionary History and Biological Regulation of CD93

CD93 is a transmembrane C-type lectin expressed on myeloid, endothelial, and B cells. First identified as a developmental B cell marker and a phagocytic C1q receptor, little is known about the role and mechanism of CD93 in efferocytosis (the phagocytosis of apoptotic cells). CD93 knockout mice develop chronic inflammatory diseases characterized by a lack of efferocytosis such as atherosclerosis and a lupus-like autoimmune disease. In humans, a cleaved form of CD93 (sCD93) is elevated during inflammation and autoimmune responses, and CD93 polymorphisms are associated with enhanced susceptibility to atherosclerosis and lupus. Despite these clinical associations, no comprehensive bioinformatic analysis of CD93’s evolution and regulation have been performed to date. To this end evolutionary analysis of CD93 was performed, demonstrating that CD93 evolution is characterized by conservation but with several amino acid residues showing recent positive selection. Promoter analysis of CD93 revealed several interactions with transcription factors involved in regulation of cell growth, differentiation, and apoptosis, consistent with the known expression profile of CD93 and cell types known to engage in efferocytosis. Shedding assays using human monocytes and monocyte-like THP-1 cells show that CD93 expression is lost during monocyte-to-macrophage differentiation and in response to PMA stimulation. The cleavage was not dependent on the TAPI-2-inhibitable proteases which includes select MMPs and other proteases such as ADAMs and ACE secretases. Importantly, apoptotic cell mimics opsonized with sCD93 containing supernatants show increased phagocytic uptake, suggesting that sCD93 acts as an opsonin for apoptotic cells

String-like Clusters and Cooperative Motion in a Model Glass-Forming Liquid

A large-scale molecular dynamics simulation is performed on a glass-forming Lennard-Jones mixture to determine the nature of dynamical heterogeneities which arise in this model fragile liquid. We observe that the most mobile particles exhibit a cooperative motion in the form of string-like paths (``strings'') whose mean length and radius of gyration increase as the liquid is cooled. The length distribution of the strings is found to be similar to that expected for the equilibrium polymerization of linear polymer chains.Comment: 6 pages of RevTex, 6 postscript figures, uses epsf.st

Chapter 10 Scholarly Practice and Meaningful Research: Utilising Voice by Enabling Action … If it was Only that Simple!

The growing importance of ‘lived practices’ in entrepreneurship-related studies has sought to pose several questions and challenges for researchers/scholars in the field (Ruona & Gilley, 2009; Short, Keefer, & Stone, 2009). The issue of how current entrepreneurship research practices can become more applied in nature provides the basis for articulating more clearly what we mean by research impact and why it has become a central concern in the research field (Beyer & Trice, 1982; Huggins et al., 2008; Rynes, 2007; Starkey & Tempest, 2005). This debate has drawn specific attention to the need for applied research in entrepreneurial scholarship, which is more reflective of lived practice. The need to reach a balance between practitioners and academics’ expectations in terms of delivering research which is focussed towards achieving academic rigour and application to practice, which is both meaningful and relatable, is significant for both communities (Ram, Edwards, Jones, Kiselinchev, & Muchenje, 2014). This chapter seeks to assist and inspire both existing and future researchers in the field to make more informed choices and offer tangible evidence of good practice, serving as a guide to researchers wishing to develop engaged research.The authors hope that the nature of this chapter would seek to clarify the importance of engaged research in supporting how we understand and respond to the needs of entrepreneurial practice as a means of building trust and confidence in research reported. A key characteristic of the issue will be the different ‘framing’ of questions that can enhance practical knowledge

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc