The Vehicle, Fall 1980

Vol. 22, No. 1 Table of Contents UntitledSusan Mehlpage 4 MitchJohn Stockmanpage 5 HallwayAndy Leszczynskipage 6 At The MoviesElise Hempelpage 8 HaikuAngie Patrickpage 8 On MagnoliasThersa Kennypage 9 NeighborJohn Stockmanpage 10 WetCathy Georgepage 10 HaikuThersa Kennypage 10 The Speed QueenCarolyn Perrypage 11 A ThoughtThersa Kennypage 14 The Stone Belongs to the LakeRobert Schumacherpage 15 Driving South of WinnipegJerry McAnultypage 16 Travels with the ExecutionerPeter Lindemanpage 17 NightwingLaura Muellerpage 18 Thoughts of an Uninterested StudentDru Seftonpage 19 Rainbird\u27s ManMary McDanielpage 20 EffortlessKevin Stottpage 25 Where the Waves SoundTheresa Whitesidepage 26 \u2745Ray Wallacepage 28 Epigram #1P. James Kruegerpage 28 UntitledSusan Mehlpage 29 RerunsAngie Patrickpage 30 SunsetGloria Rhoadspage 34 Return of the NativeRay Wallacepage 35 The GuitarJoanne Dunnepage 35 In Grandmother\u27s BedroomElise Hempelpage 36 Cindy Poem No. 3John Stockmanpage 36 Dust in the DarkLaura Muellerpage 37 Suspension BridgeLaura Henrypage 39 WavesLeslie Garnerpage 39 Oyama: a Setting and a GirlJerry McAnultypage 40 the middle of the nightKevin Stottpage 41 Old State RoadLaura Henrypage 43 Dairy QueenJohn Stockmanpage 43 Art CoverDennis Wunsch Pen and ink drawingRose Huberpage 3 PhotographIrene Brownpage 7 PhotographIrene Brownpage 27 PhotographIrene Brownpage 42 Pen and ink drawingRose Huberpage 44https://thekeep.eiu.edu/vehicle/1036/thumbnail.jp

Corporate philanthropy, political influence, and health policy

Background The Framework Convention of Tobacco Control (FCTC) provides a basis for nation states to limit the political effects of tobacco industry philanthropy, yet progress in this area is limited. This paper aims to integrate the findings of previous studies on tobacco industry philanthropy with a new analysis of British American Tobacco's (BAT) record of charitable giving to develop a general model of corporate political philanthropy that can be used to facilitate implementation of the FCTC. Method Analysis of previously confidential industry documents, BAT social and stakeholder dialogue reports, and existing tobacco industry document studies on philanthropy. Results The analysis identified six broad ways in which tobacco companies have used philanthropy politically: developing constituencies to build support for policy positions and generate third party advocacy; weakening opposing political constituencies; facilitating access and building relationships with policymakers; creating direct leverage with policymakers by providing financial subsidies to specific projects; enhancing the donor's status as a source of credible information; and shaping the tobacco control agenda by shifting thinking on the importance of regulating the market environment for tobacco and the relative risks of smoking for population health. Contemporary BAT social and stakeholder reports contain numerous examples of charitable donations that are likely to be designed to shape the tobacco control agenda, secure access and build constituencies. Conclusions and Recommendations Tobacco companies' political use of charitable donations underlines the need for tobacco industry philanthropy to be restricted via full implementation of Articles 5.3 and 13 of the FCTC. The model of tobacco industry philanthropy developed in this study can be used by public health advocates to press for implementation of the FCTC and provides a basis for analysing the political effects of charitable giving in other industry sectors which have an impact on public health such as alcohol and food

Differential Brain Development with Low and High IQ in Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development

Bacterial Effector Binding to Ribosomal Protein S3 Subverts NF-κB Function

Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC) causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome) for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC), Salmonella, Shigella, Yersinia) utilize a type III secretion system (T3SS) to inject virulence proteins (effectors) into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-κB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-κB chaperone IκBα NleH1 repressed the transcription of a RPS3/NF-κB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well as an AP-1-dependent reporter. We identified a region of NleH1 (N40-K45) that is at least partially responsible for the inhibitory activity of NleH1 toward RPS3. Deleting nleH1 from E. coli O157:H7 produced a hypervirulent phenotype in a gnotobiotic piglet model of Shiga toxin-producing E. coli infection. We suggest that NleH may disrupt host innate immune responses by binding to a cofactor of host transcriptional complexes

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