Point mutations in the C-terminus of HIV-1 gp160 reduce apoptosis and calmodulin binding without affecting viral replication

AbstractOne hallmark of AIDS progression is a decline in CD4+ T lymphocytes, though the mechanism is poorly defined. There is ample evidence that increased apoptosis is responsible for some, if not all, of the decline. Prior studies have shown that binding of cellular calmodulin to the envelope glycoprotein (Env) of HIV-1 increases sensitivity to fas-mediated apoptosis and that calmodulin antagonists can block this effect. We show that individual mutation of five residues in the C-terminal calmodulin-binding domain of Env is sufficient to significantly reduce fas-mediated apoptosis in transfected cells. The A835W mutation in the cytoplasmic domain of gp41 eliminated co-immunoprecipitation of Env with calmodulin in studies with stably transfected cells. Four point mutations (A835W, A838W, A838I, and I842R) and the corresponding region of HIV-1 HXB2 were cloned into the HIV-1 proviral vector pNL4-3 with no significant effect on viral production or envelope expression, although co-immunoprecipitation of calmodulin and Env was decreased in three of these mutant viruses. Only wild-type envelope-containing virus induced significantly elevated levels of spontaneous apoptosis by day 5 post-infection. Fas-mediated apoptosis levels positively correlated with the degree of calmodulin co-immunoprecipitation, with the lowest apoptosis levels occurring in cells infected with the A835W envelope mutation. While spontaneous apoptosis appears to be at least partially calmodulin-independent, the effects of HIV-1 Env on fas-mediated apoptosis are directly related to calmodulin binding

Career planning courses increase career readiness of graduate and postdoctoral trainees

BACKGROUND: Given national calls for intentional career development during graduate and post-graduate scientific training, this study assessed career readiness development within the context of academic career courses. The current study evaluated the effects of academic career courses offered at two institutions that were specifically designed to increase career awareness, interest, and career-related confidence among doctoral students and postdoctoral fellows. METHODS: Participants enrolled in a career course at trainees' respective academic institutions and responded to pre- and post-course surveys (n=32, n=148). The paper offers a thematic analysis of each of the two courses using an individualized learning plan career development framework and describes the results of their respective pretest-posttest evaluations which indicated increases in career readiness. RESULTS: Though the format and content provided in each course varied, participation was associated with increases in career readiness. Participants reported increased career-awareness including a greater familiarity with different types of careers overall. Furthermore, interest in tenure track faculty careers increased in both samples, which may assuage fears that exposure to diverse career pathways could reduce interest in academic careers. Transferrable skills, including career planning and awareness also significantly increased. Course participants reported an increase in the number and type of mentors they interacted with beyond their principal faculty mentor (other faculty, professional PhDs, peers, and administrative staff). CONCLUSIONS: Findings provide supporting evidence for the benefits of implementing structured career development efforts during PhD training; even with varying content, delivery methods, and instructor type, both academic career courses led to significant gains in career awareness and readiness. Successful development and delivery of academic career courses, with a focus on career planning skills, suggest that institutions can utilize these and are an effective way to prepare PhDs for their transition from training positions into careers.DP7 OD020317 - NIH HHS; P20 GM121327 - NIGMS NIH HHS; P30 CA177558 - NCI NIH HHS; R01 GM140282 - NIGMS NIH HHSPublished versio

The Anatomy of the Sympathetic Nervous System for the Cownose Ray, Rhinoptera bonasus

(Statement of Responsibility) by Keith J. Micoli(Thesis) Thesis (B.A.) -- New College of Florida, 1993(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Demski, Le