Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal degeneration, immune dysfunction, premature ageing and increased cancer risk. The gene mutated in AT, ATM, encodes a putative lipid or protein kinase. Most of the human AT patient phenotypes are recapitulated in Atm-deficient mice. Cells derived from Atm-/- mice, like those from AT patients, exhibit abnormal response to ionizing radiation. One of the known responses to ionizing radiation is the activation of a nuclear tyrosine kinase encoded by the c-abl proto-oncogene. Ionizing radiation does not activate c-Abl in cells from AT patients or in thymocytes or fibroblasts from the Atm-deficient mice. Ectopic expression of a functional ATM kinase domain corrects this defect, as it phosphorylates the c-Abl tyrosine kinase in vitro at Ser 465, leading to the activation of c-Abl. A mutant c-Abl with Ser 465 changed to Ala 465 is not activated by ionizing radiation or ATM kinase in vivo. These findings identify the c-Abl tyrosine kinase as a downstream target of phosphorylation and activation by the ATM kinase in the cellular response to ionizing radiation.

The ubiquitously expressed nonreceptor tyrosine kinase c-Abl contains three nuclear localization signals, however, it is found in both the nucleus and the cytoplasm of proliferating fibroblasts. A rapid and transient loss of c-Abl from the nucleus is observed upon the initial adhesion of fibroblasts onto a fibronectin matrix, suggesting the possibility of nuclear export [Lewis, J., Baskaran, R., Taagepera

Growth suppression by the retinoblastoma protein (RB) is dependent on its ability to form complexes with transcription regulators. At least three distinct protein-binding activities have been identified in RB: the large A/B pocket binds E2F, the A/B pocket binds the LXCXE peptide motif, and the C pocket binds the nuclear c-Abl tyrosine kinase. Substitution of Trp for Arg 661 in the B region of RB (mutant 661) inactivates both E2F and LXCXE binding. The tumor suppression function of mutant 661 is not abolished, because this allele predisposes its carriers to retinoblastoma development with a low penetrance. In cell-based assays, 661 is shown to inhibit G 1 /S progression. This low-penetrance mutant also induces terminal growth arrest with reduced but detectable activity. We have constructed mutations that disrupt C pocket activity. When overproduced, the RB C-terminal fragment did not induce terminal growth arrest but could inhibit G 1 /S progression, and this activity was abolished by the C-pocket mutations. In full-length RB, the C-pocket mutations reduced but did not abolish RB function. Interestingly, combination of the C-pocket and 661 mutations completely abolished RB's ability to cause an increase in the percentage of cells in G 1 and to induce terminal growth arrest. These results suggest that the A/B or C region can induce a prolongation of G 1 through mechanisms that are independent of each other. In contrast, long-term growth arrest requires combined activities from both regions of RB. In addition, E2F and LXCXE binding are not the only mechanisms through which RB inhibits cell growth. The C pocket also contributes to RB-mediated growth suppression.

Home care aides are on the frontlines providing care to vulnerable individuals in their homes during the COVID-19 pandemic yet are often excluded from policies to protect health care workers. The goal of this study was to examine experiences of agency-employed home care aides during the COVID-19 pandemic and to identify ways to mitigate concerns. We used an innovative journaling approach with thirty-seven aides as well as in-depth interviews with fifteen aides and leadership representatives from nine home health agencies in New York and Michigan. Workers described a range of concerns around workplace safety including uncertainty around whether a client had COVID-19, inadequate access to personal protective equipment and safe transportation, as well as fundamental changes to interactions with clients. Agencies also faced challenges acquiring personal protective equipment for their aides. This research points to needed resources to support home care aides and home health agencies both during a public health crisis and in the future.

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Food preferences, systems, and policies influence the health of individuals and communities both directly, through food consumption choices, and indirectly, through environmental, economic, and social impacts. To aid student understanding of these complex determinants of food choice, a student-driven, community-engaged learning course on food systems and food choices was developed. Guided by the socio-ecological model for health and the goals of the Emory Sustainability Initiative and supported by the Center for Community Partnerships (CFCP), the course objectives, curriculum, and activities were determined by the students in collaboration with the faculty advisor and community partners. Two central components of the course were student-led learning modules and community-engaged research on food systems. The four learning modules included: (1) determinants of individual food preference and choice; (2) food and agriculture systems; (3) food access and food justice; and (4) agricultural policy. Community research projects

The tumor suppressor gene p53 is involved in predisposition to a variety of human cancers, including those from Li-Fraumeni cancer family syndrome patients. Studies of inheritance of p53 germline mutations require confirmation of the mutation in the tumors from family members. These studies, as well as other retrospective studies of tumor specific mutations, are often hampered by a lack of available fresh or frozen tumor tissue samples for DNA extraction to confirm the suspected p53 mutation. Here we describe a simple technique for DNA isolation that permits mutational analysis of p53 from minimal amounts of paraffin-embedded archival tissue samples.