Multispecies methods, technologies for play

School of Desig

Does “Asymptomatic” Mean Without Symptoms for Those Living with HIV Infection?

Throughout the history of the HIV epidemic, HIV-positive patients with relatively high CD4 counts and no clinical features of opportunistic infections have been classified as ‘‘asymptomatic’’ by definition and treatment guidelines. This classification, however, does not take into consideration the array of symptoms that an HIV-positive person can experience long before progressing to AIDS. This short report describes two international multi-site studies conducted in 2003 - 2005 and 2005 - 2007. The results from the studies show that HIV-positive people may experience symptoms throughout the trajectory of their disease, regardless of CD4 count or classification. Providers should discuss symptoms and symptom management with their clients at all stages of the disease

ICOSL+ plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist

Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs). We performed multiparametric flow cytometry in a cohort of 156 HCT recipients and conducted experiments with aGVHD murine models to understand the role of ICOSL+ DCs. We observed an increased frequency of ICOSL+ plasmacytoid DCs, correlating with CD146+CCR5+ T cell frequencies, in the 64 HCT recipients with gastrointestinal aGVHD. In murine models, donor bone marrow cells from ICOSL-deficient mice compared to those from wild-type mice reduced aGVHD-related mortality. Reduced aGVHD resulted from lower intestinal infiltration of pDCs and pathogenic Th17 cells. We transplanted activated human ICOSL+ pDCs along with human peripheral blood mononuclear cells into immunocompromised mice and observed infiltration of intestinal CD146+CCR5+ T cells. We found that prophylactic administration of a dual human ICOS/CD28 antagonist (ALPN-101) prevented aGVHD in this model better than did the clinically approved belatacept (CTLA-4-Fc), which binds CD80 (B7-1) and CD86 (B7-2) and interferes with the CD28 T cell costimulatory pathway. When started at onset of aGVHD signs, ALPN-101 treatment alleviated symptoms of ongoing aGVHD and improved survival while preserving antitumoral cytotoxicity. Our data identified ICOSL+-pDCs as an aGVHD biomarker and suggest that coinhibition of the ICOSL/ICOS and B7/CD28 axes with one biologic drug may represent a therapeutic opportunity to prevent or treat aGVHD

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Organisms in experimental research

Rachel A. Ankeny and Sabina Leonell

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

Forage quality, intake, and digestibility of year-long pastures for steers

Thirty-six weanling steer calves (avg wt = 174 +/- 14 kg) were grazed on either wheat, irrigated improved, or native rangeland pastures from December 1989 to December 1990. Irrigated improved pastures consisted of 2 cool-season [tall wheatgrass [Agropyron elongatum (Host.) Beauv.], tall fescue (Festuca arundinacea Schreb.) 2 warm-season [bermudagrass (Cynodon dactylon (L.) Pers.], bluestem (Bothriochloa ischaemum Keng.), and annual wheat. Wheat pastures were grazed from 13 December to 11 April. Warm-season pastures were grazed from 30 May (bermudagrass) or 27 June (bluestem) until 3 October. Cool-season pastures were grazed at other days during spring and fall seasons. Rumen evacuation procedures were used to evaluate forage quality and estimate forage intake during each grazing season. Winter rangeland pastures were lower in nutritional quality (based on protein and fiber contents) and in vitro organic matter digestibility (53 vs 85%, P 0.10) in organic matter intake (% of body weight) during winter, summer, and fall season but during spring organic matter intake was greater (P < 0.10) for steers on rangeland pasture than for those on cool-season grasses.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Economics of grazing weeping lovegrass with stockers in the Southern Great Plains

Because of the relatively low cost of seed and ease of establishment, more than 0.4 million ha of weeping lovegrass (Eragrostis curvula (Shrad.) Nees.) were planted on Conservation Reserve Program (CRP) lands in the Southern High Plains. Dryland cropping alternatives including wheat and grain sorghum, give relatively low and variable economic returns. The objective of this study was to evaluate the economics of the lovegrass grazing alternative. Using a tract of weeping lovegrass in Curry County, N.M., animal performance and the economics of 5 grazing management treatments were evaluated, including 12-month and 6-month continuous grazing, seasonal grazing during only the spring and fall, and a 6-pasture rotation system. Fertilization of the pastures was also evaluated for the spring/fall grazing treatment. Average daily gain (ADG) for yearlings grazing weeping lovegrass pastures was found to decline rapidly as the grazing season progressed. The ADG was over 1.36 kg day-1 in early May but gradually declined over the grazing season to less than 0.45kg day-1 by the end of August. To maximize profit, stocker cattl ewould be sold in early September. All of the grazing systems yielded similar net economic returns, but substantially high ereconomic returns could be made by adjusting stocking rates to market conditions. Returning CRP land to dryland cropping or grazing with stocker cattle was estimated to yield nearly identical economic returns. Neither growing traditional crops or grazing lovegrass pastures appear to be economically viable alternatives without government assistance programs in place.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Economics of grazing weeping lovegrass with stockers in the Southern Great Plains

Because of the relatively low cost of seed and ease of establishment, more than 0.4 million ha of weeping lovegrass (Eragrostis curvula (Shrad.) Nees.) were planted on Conservation Reserve Program (CRP) lands in the Southern High Plains. Dryland cropping alternatives including wheat and grain sorghum, give relatively low and variable economic returns. The objective of this study was to evaluate the economics of the lovegrass grazing alternative. Using a tract of weeping lovegrass in Curry County, N.M., animal performance and the economics of 5 grazing management treatments were evaluated, including 12-month and 6-month continuous grazing, seasonal grazing during only the spring and fall, and a 6-pasture rotation system. Fertilization of the pastures was also evaluated for the spring/fall grazing treatment. Average daily gain (ADG) for yearlings grazing weeping lovegrass pastures was found to decline rapidly as the grazing season progressed. The ADG was over 1.36 kg day-1 in early May but gradually declined over the grazing season to less than 0.45kg day-1 by the end of August. To maximize profit, stocker cattl ewould be sold in early September. All of the grazing systems yielded similar net economic returns, but substantially high ereconomic returns could be made by adjusting stocking rates to market conditions. Returning CRP land to dryland cropping or grazing with stocker cattle was estimated to yield nearly identical economic returns. Neither growing traditional crops or grazing lovegrass pastures appear to be economically viable alternatives without government assistance programs in place.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202