El papel de los estudios bioarqueológicos en las interpretaciones sobre las comunidades neolíticas del noreste peninsular

Resumen del trabajo presentado al VI Congreso del Neolítico en la Península Ibérica: "Los cambios económicos y sus implicaciones sociales durante el Neolítico de la Península Ibérica", celebrado en Granada del 22 al 26 de junio de 2016.-- et al.El marco del proyecto I+D: “Aproximación a las primeras comunidades neolíticas del NE peninsular a través de sus prácticas funerarias” (2011-2015), y su continuidad para los próximos cuatro años al haber sido renovado, tiene por objetivo conocer cada día más y mejor las comunidades de agricultores y pastores que entre finales del V e inicios del IV milenio cal BC ocuparon y enterraron a sus muertos en el noreste de la Península Ibérica. El contexto de estudio es excepcional, puesto que aquellas comunidades inhumaron sistemáticamente a sus congéneres en tumbas habitualmente individuales y ocasionalmente junto a otro individuo. En esta presentación no sólo queremos mostrar los nuevos análisis y metodologías que estamos aplicando al estudio de los restos humanos, sino también el modelo de trabajo que hemos seguido. A este respecto, tres aspectos son fundamentales: 1) las dataciones absolutas son el eje que vertebra los posteriores análisis; 2) la colaboración con los distintos investigadores/as y laboratorios debe ser estrecha (no es cuestión de solicitar los resultados de un análisis a un laboratorio sino trabajar con las personas que manipulan las muestras y conocen los pros y contras de cada una de las técnicas empleadas) y 3) los estudios y análisis a realizar confluyen para responder a las hipótesis planteadas. A este respecto, en el proyecto hemos tenido la fortuna de poder colaborar con numerosos investigadores/as cuya especialidad versa alrededor de los restos funerarios y que firman la presente comunicación: análisis isotópicos, Adn, tafonomía funeraria, estudios de stress muscular y análisis de morfología dental.Peer Reviewe

The Structure of Jupiter, Saturn, and Exoplanets: Key Questions for High-Pressure Experiments

We give an overview of our current understanding of the structure of gas giant planets, from Jupiter and Saturn to extrasolar giant planets. We focus on addressing what high-pressure laboratory experiments on hydrogen and helium can help to elucidate about the structure of these planets.Comment: Invited contribution to proceedings of High Energy Density Laboratory Astrophysics, 6. Accepted to Astrophysics & Space Science. 12 page

Subject-specific computer simulation model for determining elbow loading in one-handed tennis backhand groundstrokes

This article was published in the journal Sports Biomechanics [© Taylor and Francis] and the definitive version is available from; http://www.tandfonline.com/doi/abs/10.1080/14763141.2011.629306.A subject-specific angle-driven computer model of a tennis player, combined with a forward dynamics, equipment-specific computer model of tennis ball–racket impacts, was developed to determine the effect of ball–racket impacts on loading at the elbow for one-handed backhand groundstrokes. Matching subject-specific computer simulations of a typical topspin/slice one-handed backhand groundstroke performed by an elite tennis player were done with root mean square differences between performance and matching simulations of < 0.5°over a 50 ms period starting from ball impact. Simulation results suggest that for similar ball–racket impact conditions, the difference in elbow loading for a topspin and slice one-handed backhand groundstroke is relatively small. In this study, the relatively small differences in elbow loading may be due to comparable angle–time histories at the wrist and elbow joints with the major kinematic differences occurring at the shoulder. Using a subject-specific angle-driven computer model combined with a forward dynamics, equipment-specific computer model of tennis ball–racket impacts allows peak internal loading, net impulse, and shock due to ball–racket impact to be calculated which would not otherwise be possible without impractical invasive techniques. This study provides a basis for further investigation of the factors that may increase elbow loading during tennis strokes

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

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