Interleukin 2 induces CD8+ T cell-mediated suppression of human immunodeficiency virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression.

The nonlytic suppression of human immunodeficiency virus (HIV) production from infected CD4+ T cells by CD8+ lymphocytes from HIV-infected individuals is one of the most potent host-mediated antiviral activities observed in vitro. We demonstrate that the pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent inducer of the CD8+ HIV suppressor phenomenon. IL-2 induces HIV expression in peripheral blood or lymph node mononuclear cells from HIV-infected individuals in the absence of CD8+ T cells. However, IL-2 induces CD8+ T cells to suppress HIV expression when added back to these cultures, and this effect dramatically supersedes the ability to IL-2 to induce HIV expression. Five to 25 times fewer CD8+ cells were required to obtain comparable levels of inhibition of viral production if they were activated in the presence of IL-2 as compared with IL-12 or no exogenous cytokine. Furthermore, IL-2 appeared either to induce a qualitative increase in HIV suppressor cell activity or to increase the relative frequency of suppressor cells in the activated (CD25+) CD8+ populations. Analyses of proviral levels in peripheral blood mononuclear cells suggest that CD8+ T cell-mediated lysis of in vivo infected cells is not induced by IL-2. These results have implications for our understanding of the effects of impaired IL-2 production during HIV disease as well as the overall effects of IL-2-based immunotherapy on HIV replication in vivo.

Identification and characterization of a Drosophila nuclear receptor with the ability to inhibit the ecdysone response.

In a search for retinoid X receptor-like molecules in Drosophila, we have identified an additional member of the nuclear receptor superfamily, XR78E/F. In the DNA-binding domain, XR78E/F is closely related to the mammalian receptor TR2, as well as to the nuclear receptors Coup-TF and Seven-up. We demonstrate that XR78E/F binds as a homodimer to direct repeats of the sequence AGGTCA. In transient transfection assays, XR78E/F represses ecdysone signaling in a DNA-binding-dependent fashion. XR78E/F has its highest expression in third-instar larvae and prepupae. These experiments suggest that XR78E/F may play a regulatory role in the transcriptional cascade triggered by the hormone ecdysone in Drosophila.

The ability to associate with activation domains in vitro is not required for the TATA box-binding protein to support activated transcription in vivo.

The TATA box-binding protein (TBP) interacts in vitro with the activation domains of many viral and cellular transcription factors and has been proposed to be a direct target for transcriptional activators. We have examined the functional relevance of activator-TBP association in vitro to transcriptional activation in vivo. We show that alanine substitution mutations in a single loop of TBP can disrupt its association in vitro with the activation domains of the herpes simplex virus activator VP16 and of the human tumor suppressor protein p53; these mutations do not, however, disrupt the transcriptional response of TBP to either activation domain in vivo. Moreover, we show that a region of VP16 distinct from its activation domain can also tightly associate with TBP in vitro, but fails to activate transcription in vivo. These data suggest that the ability of TBP to interact with activation domains in vitro is not directly relevant to its ability to support activated transcription in vivo.

Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts.

The RII beta regulatory subunit of cAMP-dependent protein kinase (PKA) contains an autophosphorylation site and a nuclear location signal, KKRK. We approached the structure-function analysis of RII beta by using site-directed mutagenesis. Ser114 (the autophosphorylation site) of human RII beta was replaced with Ala (RII beta-P) or Arg264 of KKRK was replaced with Met (RII beta-K). ras-transformed NIH 3T3 (DT) cells were transfected with expression vectors for RII beta, RII beta-P, and RII beta-K, and the effects on PKA isozyme distribution and transformation properties were analyzed. DT cells contained PKA-I and PKA-II isozymes in a 1:2 ratio. Over-expression of wild-type or mutant RII beta resulted in an increase in PKA-II and the elimination of PKA-I. Only wild-type RII beta cells demonstrated inhibition of both anchorage-dependent and -independent growth and phenotypic change. The growth inhibitory effect of RII beta overexpression was not due to suppression of ras expression but was correlated with nuclear accumulation of RII beta. DT cells demonstrated growth inhibition and phenotypic change upon treatment with 8-Cl-cAMP. RII beta-P or RII beta-K cells failed to respond to 8-Cl-cAMP. These data suggest that autophosphorylation and nuclear location signal sequences are integral parts of the growth regulatory mechanism of RII beta.

"i Went To The Woods Because I Wished To Live Deliberately": How A College-Level Academic Course Can Influence A Lifetime

This study, using the portraiture methodology, provides an analysis of the lifelong significance of an undergraduate program that integrates literature with an outdoor experiential platform. With limited research on long-term effects of an academic outdoor experiential course on one's life, there is space to wonder about the prospect and nature of the long-term significance of an academic course that may offer technical skill, intrapersonal and interpersonal development, and also the delivery of subject matter related to a traditional or mainstream academic area of study. Utilizing an academic skills-oriented lens as well as a character strengths lens, portraits were crafted of four former participants of the University of Michigan's New England Literature Program (NELP) to shed light on the long-term influence of this type of course, crucial participant characteristics that contribute to the program's impact, and specific components of the program that are particularly integral to the course's efficacy. Since 1975, each spring term a small contingent of students and educators has lived in the woods in the New England region as a community of learners, artists and explorers. NELP is an exemplar of a longstanding undergraduate academic English course that integrates the literature of New England writers, exploratory writing and student experiences relating to regional literature and the land. Emergent themes of this course's long-term influence on former participants include increased collaborative skills, increased self-confidence and self-knowledge, a reinforcement of lifelong relationships with the outdoors, and nurtured creativity. For participants to reap benefit from this course, it was important for them to enter with maturity to conduct themselves with openness to new experiences, relationships, and extensive reflection. Findings relating to the integral components of such a program include that of being place-based, oriented towards process, and being an intentional, collaborative community.

Will this time be different for Greece? How to assess its ability to deliver on the reform agenda. CEPS Commentary, 13 March 2015

Taking its inspiration from the ongoing debate on whether this time will be different for Greece and whether Syriza will deliver on its reform promises to the European partners, this Commentary expresses bemusement that the public debate on such an important issue as well as internal discussions among senior policy-makers frequently resort to ‘gut feelings’ or simple stereotypes. To counteract this tendency, the author presents a simple analytical framework that can be used to assess the likelihood that a government will deliver on its reform agenda. Its purpose is not to allow for a precise probabilistic calculation, but to enable better structuring of the knowledge we have. It emphasises that the change depends NOT only on the capacity of the state to design and deliver policies, but even more crucially on state autonomy from both illegitimate and legitimate interests and cognitive models used by policy-makers to make sense of the world.

Queens Borough : being a descriptive and illustrated book of the borough of Qeens, city of Greater New York, setting forth its many advantages and possibilities as a section wherein to live, to work and succeed ... /

Mode of access: Internet.

Queens Borough; being a descriptive and illustrated book of the borough of Queens, city of Greater New York, setting forth its many advantages and possibilities as a section wherein to live, to work and succeed ... Issued by the Manufacturing and industrial committee of the Chamber of commerce of the borough of Queens;

Mode of access: Internet.

Bicyclists' inclination and ability to search behind before turning left. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

How to live, rules for healthful living based on modern science;

Mode of access: Internet.

A treasury of meditation, or, Suggestions as aids to those who desire to live a devout life /

Mode of access: Internet.

The life of Jesus, and how we are to live : thirty lessons for the daily vacation Bible school /

Mode of access: Internet.

How to get started in the baby chick and poultry business; a booklet of helpful information for those men and women who are desirous of devoting their time and ability to this highly profitable, extremely modern field of business ...

Foreword signed: Wellington J. Smith.

The worth of a penny : or, a caution to keep money. With the causes of the scarcity and misery of the want thereof as also how to save it in our diet, apparel, recreation, etc. And also what honest course men in want may take to live /

Mode of access: Internet.

Rules and regulations of the Board of live stock commissioners of the state of Illinois, with extracts from the law in relation in live stock sanitation, cruelty to animals, meat inspection and other matters relating to live stock interests, 1908 ...

Mode of access: Internet.