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

Agricultural Research Bulletins, Nos. 448-488

Volume 33, Bulletins 448-488. (448) Management Aspects of School Lunch Programs in Iowa; (449) Optimum Farm Plans for Beginning Tenant Farmers on Clarion-Webster Soils (An Application of Linear Programming); (450) Farm Planning for Maximum Profits on the Cresco-Clyde Soils in Northeast Iowa, And Comparison of Farm and Nonfarm Incomes for Beginning Farmers (An Application of Linear Programming; (451) Analysis of Returns from Farm and Nonfarm Employment Opportunities on Shelby-Grundy-Haig Soils; (452) Social Status and Occupational Prospects of Married Farm Laborers in Cherokee County, Iowa 1949; (453) Load Characteristics of Selected Highly Electrified Iowa Farms; (454) Application of Input-Output Analysis to a Regional Model Stressing Agriculture; (455) Economic Optima in Soil Conservation Farming and Fertilizer Use for Farms in the Ida-Monona Soil Area of Western Iowa; (456) Plans for Beginning Farmers in Southwest Iowa with Comparison of Farm and Nonfarm Income Opportunities; (457) Seasonal Changes in Soil Moisture as Related to Rainfall, Soil Type and Crop Growth; (458) Research on Irrigation of Corn and Soybeans at Conesville and Ankeny, Iowa, 1951 to 1959; (459) Effects of the Federal Programs for Corn and Other Grains on Corn Prices, Feed Grains Production and Livestock Production; (460) Soil Erosion Control in Process in Western Iowa; (461) Relative Efficiencies of Farm Tenure Classes in Intrafirm Resource Allocation; (462) New Procedures in Estimating Feed Substitution Rates and in Determining Economic Efficiency in Pork Production: II. Replacement Rates of Corn and Soybean Oilmeal in Fortified Rations for Growing-Fattening Swine on Pasture; (463) Fertilizer Production Functions for Corn and Oats: Including an Analysis of Irrigated and Residual Response; (464) Comparison of Methods and Blowers for the Purity Analysis of Kentucky Bluegrass Seed; (465) Evaluation of Some Soil Moisture Characteristics of Iowa Soils; (466) Progress and Problems in the Iowa Soil Conservation Districts Program: A Pilot Study of the Jasper Soil Conservation District; (467) Application of Linear Programming to the Study of Supply Responses in Dairying; (468) Food Intakes of 2,189 Women in Five North Central States; (469) Input-Output Analysis Emphasizing Regional and Commodity Sectors of Agriculture; (470) Educational Needs of Three Socio-Economic Groups of Rural Homemakers in Iowa; (471) Changes in Supply Functions and Supply Elasticities in Hog Production; (472) Production Surfaces and Economic Optima for Corn Yields with Respect to Stand and Nitrogen Levels; (473) Forecasting Beef Cattle and Hog Prices by Quarter-Years; (474) Statistical Analysis of Certain Institutional Variables in the Butter and Margarine Market; (475) Use of a Dynamic Model in Programming Optimum Conservation Farm Plans on Ida-Monona Soils; (476) Alternative parity Formula for Agriculture; (477) Consumer Preferences for Pork, Des Moines, Iowa; (478) Economy of Innovations in Dairy Farming and Adjustments to Increase Resource Returns; (479) Iowa Farm Operators' and Farm Landlords' Knowledge of, Participation in and Acceptance of the Old Age and Survivors Insurance Program; (480) Adjustments to Meet Changes in Prices and to Improve Incomes on Dairy Farms in Northeastern Iowa; (481) Analysis of Income Possibilities From Farm Adjustments in Southern Iowa: Including Production of Grade B Milk; (482) Biology of a Large Mayfly, Hexagenia bilineata (Say), of the Upper Mississippi River; (483) Biology and Possible Control of Nuisance Caddisflies of the Upper Mississippi River; (484) Cometitive Position of Small Dairy Herds on North-Central Iowa Farms; (485) Theories of Choice in Relation to Farmer Decisions; (486) Profit-Maximizing Plans and Static Supply Schedules for Fluid Milk in the Des Moines Milkshed; (487) Programming Procedures for Farm and Home Planning Under Variable Price, Yield and Capital Quantities; (488) Application of Game Theory Models to Decisions on Farm Practices and Resource Use</p