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National efforts to improve equitable teaching practices in biology education have led to an increase in research on the barriers to student participation and performance, as well as solutions for overcoming these barriers. Fewer studies have examined the extent to which the resulting data trends and effective strategies are generalizable across multiple contexts or are specific to individual classrooms, institutions, or geographic regions. To address gaps in our understanding, as well as to establish baseline information about students across contexts, a working group associated with a research coordination network (Equity and Diversity in Undergraduate STEM, EDU-STEM) convened in Las Vegas, Nevada, in November of 2019. We addressed the following objectives: 1) characterize the present state of equity and diversity in undergraduate biology education research; 2) address the value of a network of educators focused on science, technology, engineering, and mathematics equity; 3) summarize the status of data collection and results; 4) identify and prioritize questions and interventions for future collaboration; and 5) construct a recruitment plan that will further the efforts of the EDU-STEM research coordination network. The report that follows is a summary of the conclusions and future directions from our discussion.

Nano- and microscale topographical cues play critical roles in the induction and maintenance of various cellular functions, including morphology, adhesion, gene regulation, and communication. Recent studies indicate that structure and function at the heart tissue level is exquisitely sensitive to mechanical cues at the nano-scale as well as at the microscale level. Although fabrication methods exist for generating topographical features for cell culture, current techniques, especially those with nanoscale resolution, are typically complex, prohibitively expensive, and not accessible to most biology laboratories. Here, we present a tunable culture platform comprised of biomimetic wrinkles that simulate the heart's complex anisotropic and multiscale architecture for facile and robust cardiac cell alignment. We demonstrate the cellular and subcellular alignment of both neonatal mouse cardiomyocytes as well as those derived from human embryonic stem cells. By mimicking the fibrillar network of the extracellular matrix, this system enables monitoring of protein localization in real time and therefore the high-resolution study of phenotypic and physiologic responses to in-vivo like topographical cues.

Phospholipase C-gamma2 (PLC-gamma2) is a key component of signal transduction in leukocytes. In natural killer (NK) cells, PLC-gamma2 is pivotal for cellular cytotoxicity; however, it is not known which steps of the cytolytic machinery it regulates. We found that PLC-gamma2-deficient NK cells formed conjugates with target cells and polarized the microtubule-organizing center, but failed to secrete cytotoxic granules, due to defective calcium mobilization. Consequently, cytotoxicity was completely abrogated in PLC-gamma2-deficient cells, regardless of whether targets expressed NKG2D ligands, missed self major histocompatibility complex (MHC) class I, or whether NK cells were stimulated with IL-2 and antibodies specific for NKR-P1C, CD16, CD244, Ly49D, and Ly49H. Defective secretion was specific to cytotoxic granules because release of IFN-gamma on stimulation with IL-12 was normal. Plcg2-/- mice could not reject MHC class I-deficient lymphoma cells nor could they control CMV infection, but they effectively contained Listeria monocytogenes infection. Our results suggest that exocytosis of cytotoxic granules, but not cellular polarization toward targets, depends on intracellular calcium rise during NK cell cytotoxicity. In vivo, PLC-gamma2 regulates selective facets of innate immunity because it is essential for NK cell responses to malignant and virally infected cells but not to bacterial infections.

We searched for clonable committed T cell progenitors in the adult mouse bone marrow and isolated rare (approximately 0.05%) cells with the Thy-1hiCD2-CD16+CD44hiCD25-Lin- phenotype. In vivo experiments showed that these cells were progenitors committed only to reconstituting the T cell lineage of irradiated Ly5 congenic hosts. Reconstitution of the thymus was minimal compared with that of the bone marrow, spleen, and lymph nodes. At limiting dilutions, donor T cell reconstitution of the spleen frequently occurred without detectable donor cells in the thymus. Progenitors were capable of rapidly reconstituting athymic hosts. In conclusion, the clonable bone marrow progenitors were capable of T cell reconstitution predominantly by means of an extrathymic pathway.

Background: Previous studies showed that a combination of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte globulin (ATG), and a single donor blood transfusion induced tolerance to ACI heart allografts in Lewis rats. All three modalities were required to achieve tolerance. The objective of the current study was to determine the subset(s) of cells in the donor blood that facilitated long-term allograft survival., Methods: Lewis hosts received TLI, ATG, and donor cell infusion after heart transplantation. Graft survival, mixed leukocyte reaction (MLR), and intragraft cytokine mRNA were studied., Results: The intravenous injection of 25 x 10(6) ACI peripheral blood mononuclear cells (PBMC) significantly prolonged graft survival as compared with that of Lewis hosts given TLI and ATG alone. Injection of highly enriched blood T cells or splenic B cells adjusted for the number contained in 25 x 10(6) PBMC failed to induce significant graft prolongation. Unexpectedly, depletion of monocytes (CD11b+ cells) from PBMC resulted in the loss of graft prolongation activity. Enriched populations of monocytes obtained by plastic adherence were more efficient in prolonging graft survival than PBMC on a per cell basis. Hosts with long-term grafts (>100-day survival) showed evidence of immune deviation, because the MLR to ACI stimulator cells was vigorous, but secretion of interferon-gamma in the MLR was markedly reduced. In situ hybridization studies of long-term grafts showed markedly reduced levels of interferon-gamma mRNA as compared with rejecting grafts., Conclusion: Infusion of donor monocytes facilitated graft prolongation via immune deviation.

Apoptosis of peripheral blood T cells has been suggested to play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Spontaneous, Fas (CD95)-induced and activation-induced T cell apoptosis have all been described in peripheral blood mononuclear cell cultures of HIV-infected individuals. We have previously shown that activation-induced T cell apoptosis is Fas independent in peripheral blood T cells from HIV+ individuals. In this study, we extend and confirm these observations by using an inhibitor of interleukin-1 beta converting enzyme (ICE) homologues. We show that z-VAD-fmk, a tripeptide inhibitor of ICE homologues, can inhibit Fas-induced apoptosis of peripheral blood CD4(+) and CD8+ T cells from asymptomatic HIV+ individuals. z-VAD-fmk also inhibited activation (anti-CD3)- induced CD4+ and CD8+ T cell apoptosis (AICD) in some but not all asymptomatic HIV+ individuals. Apoptosis was measured by multiparameter flow cytometry. The z-VAD-fmk inhibitor also enhanced survival of T cells in anti-Fas or anti-CD3 antibody-treated cultures and inhibited DNA fragmentation. AICD that could be inhibited by z-VAD-fmk was Fas independent and could be inhibited with a blocking monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a recently described member of the TNF/nerve growth factor ligand family. The above findings show that Fas-induced T cell apoptosis is ICE dependent in HIV infection. AICD can be blocked by ICE inhibitors in some patients, and this AICD is mediated by TRAIL. These results show that TRAIL can be a mediator of AICD in T cells. These different mechanisms of peripheral blood T cell apoptosis may play different roles in the pathogenesis of HIV infection.