skip to main content

Title: Disabled-2: A modular scaffold protein with multifaceted functions in signaling: Functions of Disabled-2
Publication Date:
Journal Name:
supplement S1
Page Range or eLocation-ID:
S45 to S55
Wiley Blackwell (John Wiley & Sons)
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Disabled-2 (Dab2) is an adaptor protein that regulates the extent of platelet aggregation by two mechanisms. In the first mechanism, Dab2 intracellularly downregulates the integrin αIIbβ3receptor, converting it to a low affinity state for adhesion and aggregation processes. In the second mechanism, Dab2 is released extracellularly and interacts with the pro-aggregatory mediators, the integrin αIIbβ3receptor and sulfatides, blocking their association to fibrinogen and P-selectin, respectively. Our previous research indicated that a 35-amino acid region within Dab2, which we refer to as the sulfatide-binding peptide (SBP), contains two potential sulfatide-binding motifs represented by two consecutive polybasic regions. Using molecular docking, nuclear magnetic resonance, lipid-binding assays, and surface plasmon resonance, this work identifies the critical Dab2 residues within SBP that are responsible for sulfatide binding. Molecular docking suggested that a hydrophilic region, primarily mediated by R42, is responsible for interaction with the sulfatide headgroup, whereas the C-terminal polybasic region contributes to interactions with acyl chains. Furthermore, we demonstrated that, in Dab2 SBP, R42 significantly contributes to the inhibition of platelet P-selectin surface expression. The Dab2 SBP residues that interact with sulfatides resemble those described for sphingolipid-binding in other proteins, suggesting that sulfatide-binding proteins share common binding mechanisms.

  2. Abstract Philosophers often enroll disabled bodies and minds as objects of thought in their arguments from marginal cases and in thought experiments: for example, arguments for animal ethics use cognitively disabled people as a contrast case, and Merleau-Ponty uses a blind man with a cane as an exemplar of the relationship of technology to the human, of how technology mediates. However, these philosophers enroll disabled people without engaging significantly in any way with disabled people themselves. Instead, disabled people are treated in philosophy as literal objects—and in many cases, as less than human. (This sense of a categorical difference between disabled and nondisabled people is becoming especially clear during the Covid-19 pandemic, as I write this article.) Philosophical reflection thus makes assumptions—often wrong—about disabled people’s lives, experiences, and relationships to technology. Outside of philosophy as well as in, disabled people are not regarded as experts about our own experiences and lives; our testimony is paternalistically written over. We need better consideration of disabled people as people as we consider the future. Lack of disabled people’s points of view in philosophy colors—and sometimes invalidates—views of technological change.
  3. Knitting is a popular craft that can be used to create customized fabric objects such as household items, clothing and toys. Additionally, many knitters fnd knitting to be a relaxing and calming exercise. Little is known about how disabled knitters use and beneft from knitting, and what accessibility solutions and challenges they create and encounter. We conducted interviews with 16 experienced, disabled knitters and analyzed 20 threads from six forums that discussed accessible knitting to identify how and why disabled knitters knit, and what accessibility concerns remain. We additionally conducted an iterative design case study developing knitting tools for a knitter who found existing solutions insufcient. Our innovations improved the range of stitches she could produce. We conclude by arguing for the importance of improving tools for both pattern generation and modifcation as well as adaptations or modifcations to existing tools such as looms to make it easier to track progress
  4. Contribution: This study uncovered specific benefits, challenges, and facilitators to participating in undergraduate research for physically disabled students (PDSs) taken directly from students themselves. Background: Disabled students (DSs) earn bachelor's degrees and gain employment in STEM careers at rates lower than their peers. The paradigm shift in undergraduate STEM education from lecture-based to inquiry-based learning is an opportunity to explore new options for including DSs. Little is known about designing inquiry-based learning settings for DSs. Research Question: This article seeks to increase the understanding of how to support PDSs in inquiry-based settings. Specifically, the authors documented the experiences of PDS in a summer undergraduate research program to uncover: 1) benefits they receive from participating; 2) specific challenges these students face; and 3) novel ways to facilitate participation. Methodology: The authors conducted semistructured interviews of five undergraduate PDS, who participated in a summer research program. The paper reports representative student responses across themes related to benefits, challenges, and facilitators of success in the program. Findings: The students enjoyed many benefits typically gained from undergraduate research, most notably career clarification. Additionally, the students experienced personal growth, including improved self-advocacy, increased confidence in their independence, and greater understanding of limitations. The main facilitatormore »was the positive attitudes of research mentors. A principal challenge was the lack of knowledge about disability in peers without disabilities who participated in the program.« less