Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Disparate Phylogeographic Patterns of Molecular Genetic Variation in Four Closely Related South American Small Cat Species

Tissue specimens from four species of Neotropical small cats (Oncifelis geoffroyi, N = 38; O. guigna,N = 6; Leopardus tigrinus, N = 32; Lynchailurus colocolo, N = 22) collected from throughout their distribution were examined for patterns of DNA sequence variation using three mitochondrial genes, 16S rRNA, ATP8, and NADH-5. Patterns between and among O. guigna and O. geoffroyi individuals were assessed further from size variation at 20 microsatellite loci. Phylogenetic analyses using mitochondrial DNA sequences revealed monophyletic clustering of the four species, plus evidence of natural hybridization between L. tigrinus and L. colocolo in areas of range overlap and discrete population subdivisions reflecting geographical isolation. Several commonly accepted subspecies partitions were affirmed for L. colocolo, but not for O. geoffroyi. The lack of geographical substructure in O. geoffroyi was recapitulated with the microsatellite data, as was the monophyletic clustering of O. guigna and O. geoffroyi individuals. L. tigrinus forms two phylogeographic clusters which correspond to L.t. oncilla (from Costa Rica) and L.t. guttula (from Brazil) and which have mitochondrial DNA (mtDNA) genetic distance estimates comparable to interspecific values between other ocelot lineage species. Using feline-specific calibration rates for mitochondrial DNA mutation rates, we estimated that extant lineages of O. guigna diverged 0.4 million years ago (Ma), compared with 1.7 Ma for L. colocolo, 2.0 Ma for O. geoffroyi, and 3.7 Ma for L. tigrinus

The Challenge of the Ivan Allen Jr. Legacy

Symposium held on the occasion of the 10th annual Founder's Day celebration, honoring Ivan Allen, Jr. Presented on March 15, 2010 from 9:00 - 11:30 AM in the Biltmore Hotel Imperial Ballroom.Runtime: 160:10 minutes.Opening remarks / Kenneth Knoespel -- Welcoming remarks / President G. P. Peterson -- Greetings / Jacqueline J. Royster -- Georgia Tech and The Legacy of Mayor Ivan Allen Jr. / Kenneth Knoespel -- Humanitarian Leadership on a Global Level: Georgia Tech Responds to The Challenge of the Allen Legacy. Ivan Allen College Faculty Panel Discussions Moderated by Susan Cozzens: Climate Change / Carl DiSalvo, Kirk Bowman and Marilyn Brown ; Security / Adjo Amekudzi, Adam Stulberg and Sy Goodman ; Africa / Michael Best and Fox Harwell ; Atlanta / Harley Etienne, Roberta Berry and Greg Nobels

Maya Zooarchaeology: New Directions in Method and Theory

A comprehensive work, combining traditional zooarchaeological reports and various state-of-the-art summaries of methods and theoretical perspectives. This combination of detailed discussions of basic zooarchaeological data with reviews of important themes in Maya zooarchaeology emphasizes the central issues that guide our research from basic data collection through final comparative interpretation. The chapters emphasize the newest developments in technical methods, the most recent trends in the analysis of “social zooarchaeology,” and the broadening perspectives provided by a new geographic range of investigations. The main focus of the volume remains on fostering cooperation among Mesoamerican zooarchaeologists at the levels of both preliminary analysis and final theoretical reconstruction.