886 research outputs found

    Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation

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    An as-yet-unidentified mutation, Y-linked autoimmune acceleration (Yaa), is responsible for the accelerated development of lupus-like autoimmune syndrome in mice. In view of a possible role for Yaa as a positive regulator of BCR signaling, we have explored whether the expression of the Yaa mutation affects the development and activation of transgenic autoreactive B cells expressing either 4C8 IgM anti-RBC or Sp6 IgM anti-DNA. In this study, we show that the expression of the Yaa mutation induced a lethal form of autoimmune hemolytic anemia in 4C8 transgenic C57BL/6 mice, likely as a result of activation of 4C8 anti-RBC autoreactive B cells early in life. This was further supported, although indirectly, by increased T cell-independent IgM production in spleens of nontransgenic C57BL/6 mice bearing the Yaa mutation. In contrast, Yaa failed to induce activation of Sp6 anti-DNA autoreactive B cells, consistent with a lack of increased IgM anti-DNA production in nontransgenic C57BL/6 Yaa mice. Our results suggest that Yaa can activate autoreactive B cells in a BCR-dependent manner, related to differences in the form and nature of autoantigens

    Weaving Academic Grace into the Fabric of Online Courses and Faculty Training: First-Year Engineering Student Advice for Online Faculty During the COVID-19 Pandemic and Faculty Responses

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    Background: In the spring of 2020, COVID-19 forced the majority of higher education online, resulting in a wave of new online students uniquely positioned to offer fresh perspectives and advice to faculty. Purpose: This study investigated the advice offered to online faculty by first-year engineering (FYE) students who were forced online during the pandemic and faculty ideas to address the student advice. Methods: This multi-methods study included qualitative data from 233 FYE students (in 67 teams across four class offerings) who provided advice for online faculty through an end-of-year team assignment, leveraging analytic induction methods for analysis. The Quality Matters Online Instructor Skill Set was used as the theoretical framework for viewing the student results (Quality Matters, 2016). After being presented with the student results, 41 faculty participants within two workshops brainstormed ways to respond to FYEs’ advice. Faculty workshop participants organized their own brainstorming/discussion results by themes within community documents. Results: Students forced online expressed the following needs/desires: instructional design practices appropriate for the online environment; understanding, flexibility, and patience from their faculty (which we defined as Academic Grace); instructor social presence; appropriate pedagogy for online learning environments; effective assessment; technologically capable instructors; and instructor understanding of their institutional context. Faculty advised responding to online students with more Academic Grace. Conclusions: This work reveals a new competency missing from traditional online instructor skills, that of Academic Grace. To embed Academic Grace within online courses, we propose that faculty consider a flexible bichronous model for online courses, in which students can choose to attend synchronous live lectures/classes or cover the material asynchronously at their own convenience. In this model, lecture/class recordings and supplemental asynchronous materials should be provided to foster fluid student movement between the learning modes. We also recommend online faculty training efforts include the components of Academic Grace: understanding, flexibility, and patience

    An outbreak of yellow mold of peanut seedlings in Texas

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    Yellow mold of peanut (Arachis hypogaea) seedlings caused by Aspergillus flavus was first observed during May 1984 in a commercial peanut farm in south Texas. The mold caused preemergence rotting of peanut seed and seedlings. On emerged seedlings the infection was largely restricted to cotyledons. The diseased plants were chlorotic, stunted, and leaflets were reduced in size with pointed tips and vein-clearing. Aflatoxins were found in cotyledons of infected seedlings but not in roots, hypocotyls, or leaves. A. flavus was the predominant fungus in the seed lot planted by the grower. Six isolates of A. flavus isolated from the seed and diseased seedlings were pathogenic to peanut in greenhouse tests

    Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding

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    CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22a allele has been proposed as a candidate allele for murine systemic lupus erythematosus. In this study, we explored the possible expression of aberrant forms of CD22, which differ in the N-terminal sequences constituting the ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in several Cd22a mouse strains, including C57BL/6 Cd22 congenic mice. The staining pattern of splenic B cells obtained with CY34 anti-CD22 mAb, which was expected to bind poorly to the aberrant CD22, was more heterogeneous in Cd22a mice than in Cd22b mice. Moreover, CD22 detected on B cells of Cd22a mice was expressed more weakly and as a smaller-sized protein, compared with Cd22b mice. Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22a mice carried a larger proportion of CD22 that was not bound by cis ligands on the B-cell surface than Cd22b mice. Finally, the study of C57BL/6 Cd22 congenic mice revealed that Cd22a B cells displayed a phenotype reminiscent of constitutively activated B cells (reduced surface IgM expression and augmented MHC class II expression), as reported for B cells expressing a mutant CD22 lacking the ligand-binding domain. Our demonstration that Cd22a B cells express aberrant forms of CD22, which can potentially deregulate B-cell signaling because of their decreased ligand-binding capacity, provides further support for Cd22a as a potential candidate allele for murine systemic lupus erythematosu

    Selective APRIL Blockade Delays Systemic Lupus Erythematosus in Mouse

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    SLE pathogenesis is complex, but it is now widely accepted that autoantibodies play a key role in the process by forming excessive immune complexes; their deposits within tissues leading to inflammation and functional damages. A proliferation inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily mediating antibody-producing plasma cell (PC)-survival that may be involved in the duration of pathogenic autoantibodies in lupus. We found significant increases of APRIL at the mRNA and protein levels in bone marrow but not spleen cells from NZB/W lupus mice, as compared to control mice. Selective antibody-mediated APRIL blockade delays disease development in this model by preventing proteinuria, kidney lesions, and mortality. Notably, this was achieved by decreasing anti-DNA and anti-chromatin autoantibody levels, without any perturbation of B- and T- cell homeostasis. Thus, anti-APRIL treatment may constitute an alternative therapy in SLE highly specific to PCs compared to other B-cell targeting therapies tested in this disease, and likely to be associated with less adverse effects than any anti-inflammatory and immunosuppressant agents previously used
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