Faculty Recital: Timothy Bostwick, Baritone; Elizabeth Thompson, Voice; Michael McAndrew, Pianist; March 21, 2023

Center for the Performing ArtsMarch 21, 2023Tuesday Evening7:00 p.m

Laurie\u27s Greenhouse

Pottery by: Elizabeth McAndrew Photography by: Kelsey Albert and Elizabeth McAndrew Modeling: Laurie the Bird Materials: Wheel thrown pottery - Cone 10 white clay and dipped glaze (cobalt blue and mossy green). Philodendron Heartleaf Plant. Laurie is a parrotlet, which is the second smallest species of parrot. Photo editing was done directly on the iPhone photo application. This photo represents beginnings because it includes many elements of my life that I drew toward me in the year that I began my medical career. Living alone for the first time, I bought plants so that I wasn\u27t the only living thing in my apartment. Then when that wasn\u27t enough, I got Laurie the Bird. Over the summer I resumed a life-long passion for pottery so that I have an outlet for creativity. Finally, I took this photo with the help of my friend and neighbor, who has been one of the best people to take study breaks with. All of these things help me ward off burn out and remember that there is much more to life and to me then studying

Enhanced Phagocytic Activity of HIV-Specific Antibodies Correlates with Natural Production of Immunoglobulins with Skewed Affinity for FcγR2a and FcγR2b

While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both quantitative differences in the capacity of antibodies to drive phagocytosis and qualitative differences in their FcγR usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc domain glycosylation, and skewed interactions with FcγR2a and FcγR2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis—driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response

Innovating Pedagogy 2015: Open University Innovation Report 4

This series of reports explores new forms of teaching, learning and assessment for an interactive world, to guide teachers and policy makers in productive innovation. This fourth report proposes ten innovations that are already in currency but have not yet had a profound influence on education. To produce it, a group of academics at the Institute of Educational Technology in The Open University collaborated with researchers from the Center for Technology in Learning at SRI International. We proposed a long list of new educational terms, theories, and practices. We then pared these down to ten that have the potential to provoke major shifts in educational practice, particularly in post-school education. Lastly, we drew on published and unpublished writings to compile the ten sketches of new pedagogies that might transform education. These are summarised below in an approximate order of immediacy and timescale to widespread implementation

High Avidity CD8+ T Cells Efficiently Eliminate Motile HIV-Infected Targets and Execute a Locally Focused Program of Anti-Viral Function

The dissemination of HIV from an initial site of infection is facilitated by motile HIV-infected CD4+ T-cells. However, the impact of infected target cell migration on antigen recognition by HIV-specific CD8+ T-cells is unclear. Using a 3D in vitro model of tissue, we visualized dynamic interactions between HIV-infected or peptide-pulsed CD4+ T-cells and HIV-specific CD8+ T-cells. CTLs engaged motile HIV-infected targets, but ∼50% of targets broke contact and escaped. In contrast, immobilized target cells were readily killed, indicating target motility directly inhibits CD8+ T-cell function. Strong calcium signals occurred in CTLs killing a motile target but calcium signaling was weak or absent in CTLs which permitted target escape. Neutralization of adhesion receptors LFA-1 and CD58 inhibited CD8+ T-cell function within the 3D matrix, demonstrating that efficient motile target lysis as dependent on adhesive engagement of targets. Antigen sensitivity (a convolution of antigen density, TCR avidity and CD8 coreceptor binding) is also critical for target recognition. We modulated this parameter (known as functional avidity but referred to here as “avidity” for the sake of simplicity) by exploiting common HIV escape mutations and measured their impact on CTL function at the single-cell level. Targets pulsed with low avidity mutant antigens frequently escaped while CTLs killed targets bearing high avidity antigen with near-perfect efficiency. CTLs engaged, arrested, and killed an initial target bearing high avidity antigen within minutes, but serial killing was surprisingly rare. CD8 cells remained committed to their initial dead target for hours, accumulating TCR signals that sustained secretion of soluble antiviral factors. These data indicate that high-avidity CD8+ T-cells execute an antiviral program in the precise location where antigen has been sensed: CTL effector functions are spatiotemporally coordinated with an early lytic phase followed by a sustained stationary secretory phase to control local viral infection

Reviews

Reviews of International and comparative industrial relations, Tatau Tatau - one big union altogether, Remedy for present evils: a history of the New Zealand Public Service Association from 1890, Sexual harassment in the workplace, Employee selection, Legislating for workplace hazards in New Zealand: overseas experience and our present and future needs, People and enterprises - human behaviour in New Zealand organisations and From school to unemployment? The labour market for young peopl

A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples

Phagocytosis can be induced via the engagement of Fcγ receptors by antibody-opsonized material. Furthermore, the efficiency of antibody-induced effector functions has been shown to be dramatically modulated by changes in antibody glycosylation. Because infection can modulate antibody glycans, which in turn modulate antibody functions, assays capable of determining the induction of effector functions rather than neutralization or titer provide a valuable opportunity to more fully characterize the quality of the adaptive immune response. Here we describe a robust and high-throughput flow cytometric assay to define the phagocytic activity of antigen-specific antibodies from clinical samples. This assay employs a monocytic cell line that expresses numerous Fc receptors: including inhibitory and activating, and high and low affinity receptors—allowing complex phenotypes to be studied. We demonstrate the adaptability of this high-throughput, flow-based assay to measure antigen-specific antibody-mediated phagocytosis against an array of viruses, including influenza, HIV, and dengue. The phagocytosis assay format further allows for simultaneous analysis of cytokine release, as well as determination of the role of specific Fcγ-receptor subtypes, making it a highly useful system for parsing differences in the ability of clinical and vaccine induced antibody samples to recruit this critical effector function.Neutralizing Antibody Consortium (International AIDS Vaccine Initiative)National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (AI055332)National Institutes of Health (U.S.) (AI080289)Ragon Institute of MGH, MIT and Harvar