The Vehicle, Fall 1987

Table of Contents Sketches in the SunRodger L. Patiencepage 3 Reflecting PoolRob Montgomerypage 5 Grandpa\u27s Porcelain DollRichard E. Hallpage 6 Tintype 1837Catherine Friemannpage 6 PhotographSteven M. Beamerpage 7 Washerwoman\u27s SongBob Zordanipage 8 Scrambled Eggs for D.O.Lynne A. Rafoolpage 8 my mother would sayMonica Grothpage 9 Retired by His ChildrenDan Von Holtenpage 10 I am the oldestMonica Grothpage 11 Ice on WheatRob Montgomerypage 12 The Nature of the RoseTroy Mayfieldpage 12 Past NebraskaDan Hornbostelpage 13 Five Minute Jamaican VacationChristy Dunphypage 14 PhotographSteven M. Beamerpage 14 The Angry PoemChristy Dunphypage 15 Road UnfamiliarChristy Dunphypage 15 raised voicesMonica Grothpage 16 Old Ladies & MiniskirtsKara Shannonpage 17 FreakspeakBob Zordanipage 18 PortraitDan Von Holtenpage 18 Mobile VacuumKathleen L. Fairfieldpage 19 Rev. Fermus DickSteve Hagemannpage 20 PhotographSteven M. Beamerpage 21 What\u27s the Name of That Flower?Richard Jesse Davispage 22 RequestChristy Dunphypage 23 SketchPaul Seabaughpage 24 ExperiencedMarilyn Wilsonpage 26 Leaving: Two ViewsTina Phillipspage 27 AntaeusDan Von Holtenpage 28 Misogyny at 19J. D. Finfrockpage 29 A Mental CrippleSteve Hagemannpage 32 AssociationsRhonda Ealypage 33 Banana BreadGail Bowerpage 34 Bill and JackBradford B. Autenpage 35 After Image No. 2Rob Montgomerypage 35 VrrooomBeth Goodmanpage 36 Mr. Modern LoverMolly Maddenpage 36 TravelogueRodger L. Patiencepage 37 Down the HighwayJoan Sebastianpage 38 A Retread HeavenRob Montgomerypage 41 StuporDan Von Holtenpage 42 Love Poem After a Seizure in Your BedBob Zordanipage 43 PalsyChristy Dunphypage 44 Interview with Mr. MatthewsBob Zordanipage 45 Chasing Down Hot Air Balloons on a Sunday MorningRob Montgomerypage 48https://thekeep.eiu.edu/vehicle/1049/thumbnail.jp

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene

Beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1−/−) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1+/+) mice efficiently cleave BC. Bcmo1−/− mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1−/− mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1−/− mice and Bcmo1+/+ mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1−/− mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1−/− mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1−/− mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1

A trajectories of behavior, attention, social and emotional problems from childhood to early adulthood following extremely preterm birth: a prospective cohort study

© 2018, The Author(s). To investigate trajectories of behavior, attention, social and emotional problems to early adulthood in extremely preterm survivors compared to a term-born comparison group. Longitudinal analysis of a prospective, population-based cohort of 315 surviving infants born < 26 completed weeks of gestation recruited at birth in 1995, from the UK/Republic of Ireland, and a term-born comparison group recruited at age 6. The parent-report Strengths and Difficulties Questionnaire was completed at age 6, 11, 16 and 19 years. The Total Behavioral Difficulties Score was 4.81 points higher in extremely preterm individuals compared to their term-born peers over the period (95% CI 3.76–5.87, p < 0.001) and trajectories were stable in both groups. The impact of difficulties on home life, friendships, school or work and/or leisure activities was greater in the EPT group (RR 4.28, 95% CI 2.89–6.35, p < 0.001), and hyperactivity/inattention and peer problems accounted for the largest differences. A clinically significant behavioral screen at age 2.5 was associated with a higher Total Behavioral Difficulties Score from 6 years onwards in extremely preterm participants (Mean difference 6.90, 95% CI 5.01–8.70, p < 0.0.01), as was moderate/severe cognitive impairment at last assessment (Mean difference: 4.27, 95% CI 2.76–5.77, p < 0.001). Attention, social and emotional problems in extremely preterm individuals persist into early adulthood with significant impact on daily life. A positive behavioral screen in infancy and moderate/severe cognitive impairment are associated with early adult outcomes.NIHR Doctoral Research Fellowship, NIHRDRF-2012-05-206. The EPICure Study was funded by a Medical Research Council Programme Grant to NM (Ref no: MR/J01107X/1

Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus