The National Park Service at 100

In its first century, the National Park Service was transformed from an agency that managed a small number of western parks to one responsible for over 400 sites across the country. The management of these park sites has changed as well, with many new parks structured as a partnership effort between the National Park Service and surrounding cities and towns, as well as non-profit organizations and friends groups. The Park Service has had its work extended by Congress to reach beyond park boundaries in order to help states and local governments with resource preservation and the development of recreational opportunities in neighborhoods where people live and work. The Park Service has also been given a leadership role in providing technical assistance to other countries in creating national parks and preserving their natural and cultural resources. As the National Park Service enters its second century, it faces many of the same challenges as other federal agencies. The two primary challenges facing the National Park Service as it moves forward are ensuring sufficient funding for the national park system from Congress and other revenue sources and keeping the national parks relevant to succeeding generations of Americans. National parks remain popular with the American public for the way they connect us to the land and the story of our country. Perhaps former National Park Service Director George Hartzog stated it best when he said: “The national park idea has been nurtured by each succeeding generation of Americans. Today, across our land, the National Park System represents America at its best. Each park contributes to a deeper understanding of the history of the United States and our way of life; of the natural processes which have given form to our land, and to the enrichment of the environment in which we live.

The Path of the Presidio Trust Legislation

Creating the Presidio Trust and enacting the other land protection measures in the Omnibus Parks Act was not been simple. The park service had originally envisioned in the general management plan for the Presidio that a partnership institution would be created to assist the National Park Service with management of the area. The park service\u27s partnership idea would be changed substantially when the trust legislation emerged from Congress. This article will examine how the Presidio first became part of the National Park System, the efforts undertaken to provide the park service with the authority needed to manage the area, and the controversies and compromises that surrounded the enactment of the Presidio Trust legislation

The Path of the Presidio Trust Legislation

Creating the Presidio Trust and enacting the other land protection measures in the Omnibus Parks Act was not been simple. The park service had originally envisioned in the general management plan for the Presidio that a partnership institution would be created to assist the National Park Service with management of the area. The park service\u27s partnership idea would be changed substantially when the trust legislation emerged from Congress. This article will examine how the Presidio first became part of the National Park System, the efforts undertaken to provide the park service with the authority needed to manage the area, and the controversies and compromises that surrounded the enactment of the Presidio Trust legislation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Cullins 3a and 3b assemble with members of the broad complex/tramtrack/bric-a-brac (BTB) protein family to form essential ubiquitin-protein ligases (E3s) in Arabidopsis

Selective modification of proteins by ubiquitination is directed by diverse families of ubiquitin-protein ligases (or E3s). A large collection of E3s use Cullins (CULs) as scaffolds to form multisubunit E3 complexes in which the CUL binds a target recognition subcomplex and the RBX1 docking protein, which delivers the activated ubiquitin moiety. Arabidopsis and rice contain a large collection of CUL isoforms, indicating that multiple CUL-based E3s exist in plants. Here we show that Arabidopsis CUL3a and CUL3b associate with RBX1 and members of the broad complex/tramtrack/bric-a-brac (BTB) protein family to form BTB E3s. Eighty genes encoding BTB domain-containing proteins were identified in the Arabidopsis genome, indicating that a diverse array of BTB E3s is possible. In addition to the BTB domain, the encoded proteins also contain various other interaction motifs that likely serve as target recognition elements. DNA microarray analyses show that BTB genes are expressed widely in the plant and that tissue-specific and isoform-specific patterns exist. Arabidopsis defective in both CUL3a and CUL3b are embryo-lethal, indicating that BTB E3s are essential for plant development