CD105 Deficieny in Mouse Aorta-derived Mesenchymal Stem Cells Promotes An Enhanced Inflammatory Response to Lipolysaccharide.

Mesenchymal stem cells (MSCs) are being widely studied for their ability to regulate macrophage cell responses. Previous works have demonstrated that mouse aorta-derived MSC (mAo-MSC) support the macrophage inflammatory response. mAo-MSC have been characterized phenotypically for MSC-associated surface antigens and express CD90 and CD105 but do not express CD73. CD105, also known as endoglin, is a coreceptor in the TGFβ superfamily of receptors. Mouse adipose-derived MSC lacking CD105 have an increased capacity to regulate T-cells by reducing their proliferation while elevated CD105 expression is consistently associated with inflammatory disease. Therefore, we hypothesized that suppression of CD105 in mAo-MSC will reduce the immunosupportive capacity of the mAo-MSC. We used siRNA to reduce expression of CD105 in mAo- MSC and subsequently examined the effect of this deficiency on their response to lipopolysaccharide (LPS) and their ability to support the macrophage inflammatory response. Contrary to our hypothesis, CD105 deficient mAo-MSC cultured alone and in co-culture with macrophage secreted increased levels of the inflammatory indicators nitric oxide (NO) and interleukin 6 (IL-6) after exposure to LPS. The increase in NO and IL-6 observed in the co-cultures is additive and therefore points to the mAo- MSC as the primary origin. Overall our data suggest that CD105 acts as a regulator of the TLR-4 pathway and may represent an important target for modification of MSC to be used in therapeutics

UNC-Emory Infant Atlases for Macaque Brain Image Analysis: Postnatal Brain Development through 12 Months

Computational anatomical atlases have shown to be of immense value in neuroimaging as they provide age appropriate reference spaces alongside ancillary anatomical information for automated analysis such as subcortical structural definitions, cortical parcellations or white fiber tract regions. Standard workflows in neuroimaging necessitate such atlases to be appropriately selected for the subject population of interest. This is especially of importance in early postnatal brain development, where rapid changes in brain shape and appearance render neuroimaging workflows sensitive to the appropriate atlas choice. We present here a set of novel computation atlases for structural MRI and Diffusion Tensor Imaging as crucial resource for the analysis of MRI data from non-human primate rhesus monkey (Macaca mulatta) data in early postnatal brain development. Forty socially-housed infant macaques were scanned longitudinally at ages 2 weeks, 3, 6, and 12 months in order to create cross-sectional structural and DTI atlases via unbiased atlas building at each of these ages. Probabilistic spatial prior definitions for the major tissue classes were trained on each atlas with expert manual segmentations. In this article we present the development and use of these atlases with publicly available tools, as well as the atlases themselves, which are publicly disseminated to the scientific community

The Vehicle, Fall 2002

Table of Contents Caterpillar DreamsAubrey Bonannopage 4 GrandmotherNatalie Espositopage 5 PhotographNatalie Espositopage 5 For My SisterAnn Hudsonpage 6 BuckeyeCaleb Judypage 6 A Moment\u27s GlowMelissa Knoblockpage 7 April 8,1994Andy Kochpage 8 Koch FuneralsAndy Kochpage 9 Grandpa Koch\u27s Sense of HumorAndy Kochpage 10 DeparturesDave Moutraypage 11 1958 VetteAlex Nicolpage 11 HomelandDave Moutraypage 12 The TravelerDave Moutraypage 12 GrandpaJennifer Probstpage 13 Confusion upon LearningJody Sanchezpage 14 Chucktown PrideMike Scalespage 14 I Might be WrongDallas Schumacherpage 15-20 UntitledAlex Nicholpage 21 Late NightRachel Seftonpage 22 Old DreamsRachel Seftonpage 23 Two-Minded ThoughtsRachel Sefton & Jodi Sanchezpage 24 Strange GraffitiMike Scalespage 24 On PoetryNick Slicerpage 25-26 Sometimes Things Just Happen That WayThomas Webbpage 26-33 Biographiespage 34-35 Editor\u27s Notepage 36https://thekeep.eiu.edu/vehicle/1076/thumbnail.jp

Imaging of Transmetallation and Chelation Phenomena Involving Radiological Contrast Agents in Mineral-Rich Fruits

Exogenous heavy metals or non-metallic waste products, for example lanthanide or iodinated contrast media for radiological procedures, may interfere with the biochemical pools in patients and in common food sources, creating an excess buildup of exogenous compounds which may reach toxic levels. Although the mechanisms are unknown, our experiments were designed to test if this toxicity can be attributed to “transmetallation” or “chelation” reactions freeing up lanthanides or chelated transition metals in acidic fruits used as phantoms representing the biologically active and mineral-rich carbohydrate matrix. The rapid breakdown of stable contrast agents have been reported at a lower pH. The interaction of such agents with native metals was examined by direct imaging of contrast infused fresh apples and sweet potatoes using low energy X-rays (40–44 kVp) and by magnetic resonance imaging at 1.5 and 3T. The stability of the exogenous agents seemed to depend on endogenous counterions and biometals in these fruits. Proton spin echo MR intensity is sensitive to paramagnetic minerals and low energy X-ray photons are sensitively absorbed by photoelectric effects in all abundant minerals and were compared before and after the infusion of radiologic contrasts. Endogenous iron and manganese are believed to accumulate due to interactions with exogenous iodine and gadolinium in and around the infusion spots. X-ray imaging had lower sensitivity (detection limit approximately 1 part in 104), while MRI sensitivity was two orders of magnitude higher (approximately 1 part in 106), but only for paramagnetic minerals like Mn and Fe in our samples. MRI evidence of such a release of metal ions from the native pool implicates transmetallation and chelation reactions that were triggered by infused contrast agents. Since Fe and Mn play significant roles in the function of metalloenzymes, our results suggest that transmetallation and chelation could be a plausible mechanism for contrast induced toxicity in vivo

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

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

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

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

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies