FADD and its Phosphorylation Mediate Mitogenic Signaling in Mutant Kras Tumors.

Fas-Associated Death Domain (FADD) through its function as an adapter protein is a key mediator of cell death. Paradoxically, amplification of its locus on 11q13.3, increased mRNA and protein expression, phosphorylation at Serine 194 (S194) and subsequent nuclear translocation has been linked with aggressive disease and poor outcomes in patients with lung as well as head and neck as cancer. To investigate a role for FADD in oncogenesis, we genetically engineered a conditional mouse model of mutant Kras-driven lung cancer wherein Fadd expression could be abrogated simultaneously with activation of mutant Kras. In the absence of FADD, a decrease in the number of lung lesions and a slower growth rate was observed. Tumors from Fadd-null animals exhibited a lower proliferative index and muted activation of downstream effectors of the RAS-mitogen-activated protein kinase (MAPK) pathway, including phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2), phosphorylated retinoblastoma (pRB) and Cyclin D1, indicating alterations in cell proliferation. In support, analysis of the FADD-interactome revealed its association with Polo-like Kinase 1(PLK1), Aurora Kinase A (AURKA), Budding Uninhibited by Benzimidazoles 1(BUB1) and CDC20, important regulators of the G2/M transition. A requirement for FADD in G2/M was further supported by the arrest of Fadd-null mouse embryonic fibroblasts at G2/M and the observation that phosphorylation of FADD at S194 preceded phosphorylation of phospho-histone H3. Heterologous expression of FADD in Fadd-null cells restored the progression of cells through G2/M and proliferation of mutant Kras expressing cells. Conditional deletion of Casein Kinase 1 alpha simultaneous with activation of mutant Kras, identified it as the kinase required for FADD-phosphorylation. Mice lacking Casein Kinase 1 alpha failed to develop adenomas but had hyperplastic lesions despite the expression of mutant Kras. These studies identify the significance of FADD and its phosphorylation by Casein Kinase 1 alpha in Kras-mediated oncogenic transformation and therefore a target for therapeutic intervention in lung cancer.PhDBiological ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111476/1/bowbritt_1.pd

Social Media for Government: Theory and Practice

Book review of Social Media for Government: Theory and Practice, by Staci M. Zavattaro and Thomas A. Brye

Facebook Activity of Oklahoma Agritourism Operations

Agritourism is an expanding industry in rural areas. Agritourism operators seek to efficiently market their operations and reach consumers far removed from agriculture. Social media serves a crucial role in tourism marketing; however, limited research exists on agritourism marketing to advise agritourism operators or those who advise agritourism operators. A quantitative content analysis was performed on 174 Oklahoman agritourism operation Facebook pages to describe posts, events, and business information created during the month of June 2018.Pages with at least one original post had more page likes than pages without. Amongst farm types, hunting agritourism operations had the lowest proportion of pages with at least one original post, while farm-to-table agritourism operations had the highest proportion. Number of reviews had a very strong relationship to total page likes, while other factors such as number of community and event posts had only a moderate relationship to page likes. Events were not frequent on Oklahoma agritourism Facebook pages, and overall page activity did not have a relationship with the number of people interested in going to events. Amongst original posts, posts created by the agritourism operator were most frequent, followed by posts shared from other sources. Pages with at least one live video or post about an event were most active. Hashtags were infrequently observed amongst Facebook posts, with limited consistency within individual pages or across multiple pages. Pages with an advertisement had more page likes than pages without advertisements.Recommendations to agritourism operators include encouraging agritourism visitors to create Facebook content, utilizing Facebook advertisements, and creating at least one original post. Additionally, agritourism operators should create a variety of types of original posts and utilize advertisements. Perhaps most important, agritourism operations should be wary of emphasizing quantity over quality in Facebook marketing. Future research should qualitatively describe Facebook pages and interview agritourism operators and visitors. Additionally, comparing Facebook data to "real life" data, such as business revenue/expense and number of visitors, could further measure the effective of various Facebook marketing practices

Small molecule screen identifies pyrimethamine as an inhibitor of NRF2-driven esophageal hyperplasia

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2 DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays. RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as potential NRF2 inhibitors with minimal cytotoxicity at specified concentrations. We then validated two of these compounds, pyrimethamine and mitoxantrone, by demonstrating their dose- and time-dependent inhibitory effects on the expression of NRF2 and its target genes in two NRF2 CONCLUSION: We have identified and validated pyrimethamine as an NRF2 inhibitor that may be rapidly tested in the clinic for NRF

Facebook Activity of Oklahoma Agritourism Facebook Pages

Agritourism is recreational travel for agricultural activities. Agricultural operations benefit from income diversification, the public receives hands-on agricultural experiences, and rural communities benefit from economic development. However, agritourism operators have reported challenges in marketing. As social media becomes increasingly important in tourism marketing, the purpose of this research is to describe overall Facebook activity related to Oklahoma agritourism. A quantitative content analysis was conducted on 174 Facebook pages of Oklahoma agritourism operations to describe posts, public interaction, events, and advertisements. Oklahoma agritourism operations had a mean of 1,330 page likes, and 69% of Facebook pages had posts during the sample period of June 2018. Pages with at least one post had more than three times the number of page likes as pages without any posts. Amongst variables compared, user-generated content in the form of community posts and reviews had the strongest influence on overall page likes. Overall Facebook activity did not influence the number of people who were interested in an event, but there was a relationship between the number of people interested and timing of event posts. Additionally, pages with advertisements had more overall page likes but posted fewer times. Agritourism operators should encourage user-generated content, develop events, create at least one post, and consider sponsoring Facebook advertisements. Future research should describe post content, further explore the relationship of Facebook activity to overall page likes, and consider a sampling period outside of June to accommodate the possibility of seasonal fluctuations

Comparison of Extension Personnel and Supervisor Perceptions of Communications Activities

Extension is often called the “best-kept secret” having low awareness with the public but high satisfaction with clientele. Extension services nationwide have faced budget cuts, creating a need for the organization to re-evaluate its activities, including how it communicates with its stakeholders. While Extension personnel are the ones who will do most of the communicating, their supervisors impact the personnel’s actions, which means it is important to assess both groups. A survey was conducted with Extension personnel and their supervisors in Mississippi assessing engagement in communications activities and perceptions of those activities, as well as personnel’s preference of professional development activities. Personnel reported higher use, comfort, and importance of more traditional (e.g. making a speech) and written activities (e.g. writing a promotional handout) than media-relations activities (e.g. being interviewed for TV), social media-related activities (e.g. managing a Twitter account), and visual communication activities (e.g. graphic design). Supervisors perceived individual communications activities as less important overall than personnel did, and although supervisor and communication scores for use and comfort/capability were similar for most communication activities, there were noticeable exceptions. Additionally, personnel preferred professional development activities that were hands-on or showing the activities first-hand (e.g. demonstrations and field days). Future research should be expanded to other states, conducted in a case study format to study specific relationships, and involve qualitative components. Extension should ensure clear supervisor-communication dialogue on prioritizing communication activities, provide training on communication activities with low use and comfort, and utilize early innovators who are comfortable using newer communication activities

New Tricks (2016)

25 years ago, a group of students began the Literary Stunt Dogs, a club for students who wanted to establish a way to share poems, short stories, art pieces, and photography made by the individuals in the community of Dakota State University. Then, in spring of 1992, the first issue of New Tricks was published. Today, the 2016 Literary Stunt Dogs are proud to bring you yet another engaging and entertaining issue filled with works created by students, faculty, staff, and other DSU members. In addition to the print copy, we are now offering our works online as well. Please enjoy all this issue has to offer, and take a closer look at these works and many others that have been published on our website, www.new-tricks.org

Empowerment or Exploitation? Ethical Engagement of Survivor Leaders in Anti-Trafficking Organizations

In recent years, anti-trafficking organizations have increased the use of survivor voices in fundraising, direct service, and leadership. While empowerment is the goal, tokenism can be the outcome when organizations do not engage survivors ethically. This integrative literature review article provides an overview of the research on engagement of sex trafficking survivors in organizations leading anti-trafficking efforts in the United States and summarizes findings to emphasize ethical engagement practices from an organizational culture perspective. Overall, it is recommended that organizations ethically engage survivors in a variety of roles within the organization. To do this well, organizations should create opportunities for professional capacity building, enhancement of survivor leadership roles and responsibilities, and adoption of a trauma-informed and survivor-informed organizational culture to empower survivors

Characteristics of Oklahoma Agritourism Facebook Posts

Agritourism is recreational travel for agricultural activities. While it provides many benefits, such as rural development and heritage preservation, many agritourism operators express challenges in marketing their operations. Social media is increasingly common in tourism marketing, but little research exists describing current marketing practices. Quantitative content analysis was used to describe 174 Oklahoma agritourism operations’ Facebook page activity in June 2018. Original posts created by the agritourism operations and community posts created by the general public had similar amounts of public interaction. Post interactions were not related to post length, and original post interactions were also not related to overall page likes. Live videos and traditional posts received the most interaction amongst types of original posts. Facebook event posts made by the agritourism operation received more public interaction than event posts made by the general public. Agritourism operators should focus on quality over quantity of information and be wary of creating posts in an “echo chamber” as only a small proportion of a large page following interact with posts. Marketing practitioners should avoid providing one-size-fits-all advice in Facebook marketing, as there was a large variety of Facebook activity observed. Future research should more specifically describe content of posts and consider perspectives of agritourism operators and visitors towards current Facebook marketing strategies

Improved Functional Prediction of Hypothetical Proteins from \u3ci\u3eListeria monocytogenes\u3c/i\u3e 08-5578

Listeria monocytogenes is a foodborne human pathogen responsible for listerosis. The genomes of several L. monocytogenes strains have been recently sequenced. The genome of L. monocytogenes 08-5578, which was in part responsible for a significant listerosis outbreak in 2008, contains an unexpectedly high percentage of protein-encoding genes (1,927 out of 3,161; 60.96%) autonomously annotated as hypothetical proteins. The aim of this study was to test whether a manual annotation strategy could be used to assign more meaningful functional names to the hypothetical proteins of 08-5578. A holistic, manual gene annotation strategy that utilized sequence homology, cellular localization predictions, structure-based evidence, phylogeny, and proteinprotein interaction data was used to assign potential cellular roles to 79 out of 100 hypothetical proteins randomly selected from the genome of 08-5578. Of significance, 5 of the 79 hypothetical proteins assigned a more meaningful name may contribute to the virulence of L. monocytogenes 08-5578, by contributing to chemotaxis, cell surface protein sorting, cell wall biosynthesis, and cold adaptation. The findings here support the notion that manual annotations, using a combination of diverse bioinformatics tools, can improve the quality of genomic information provided by automated genome annotation methods alone