First International Microgravity Laboratory

This colorful booklet presents capsule information on every aspect of the International Microgravity Laboratory (IML). As part of Spacelab, IML is divided into Life Science Experiments and Materials Science Experiments. Because the life and materials sciences use different Spacelab resources, they are logically paired on the IML missions. Life science investigations generally require significant crew involvement, and crew members often participate as test subjects or operators. Materials missions capitalize on these complementary experiments. International cooperation consists in participation by the European Space Agency, Canada, France, Germany, and Japan who are all partners in developing hardware and experiments of IML missions. IML experiments are crucial to future space ventures, like the development of Space Station Freedom, the establishment of lunar colonies, and the exploration of other planets. Principal investigators are identified for each experiment

The role of HLA-G in human pregnancy

Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy

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

Preliminary assessment of the economic impacts of alcohol pricing policy options in the UK

Alcohol has an important economic and socio-cultural place in the UK. It creates jobs, generates fiscal revenues in the form of alcohol taxes, and contributed around £2.7 billion2 in 2007 to the economy through trade (ONS, 2007b). Alcohol is shared in social interactions, and is drunk as an accompaniment to meals. While alcohol has been, and continues to be, consumed in an unproblematic way by many people, a proportion of alcohol consumption is problematic and generates harms for individuals and society. Alcohol misuse is high in the UK policy agenda. According to data from the World Health Organization (WHO), alcohol consumption in the UK increased by approximately 4 percent between 1985 and 2003, whereas it decreased over the same period for most other European Union countries (Rabinovich et al., 2009). At the same time, some alcoholrelated harms have grown over this period; for example, there were 8,758 deaths from alcohol-related causes in the UK in 2006, twice as many as there were 15 years before (National Audit Office, 2008). While there is a large body of literature focusing on the variety and extent of the public health and criminal justice impacts of alcohol use, its economic impact has received relatively less attention. In order to help Government assess the full range of implications from proposed alcohol pricing policies, RAND Europe has undertaken this study to provide evidence in the area of potential economic impacts of the following three pricing policy options: minimum pricing, ban on below-cost sales, and taxation

An embryo lethal transgenic line manifests global expression changes and elevated protein/oil ratios in heterozygous soybean plants.

Understanding the molecular processes of seed development is important especially in agronomic crops that produce large amounts of nutrient reserves. Because soybean is a vital source of vegetable protein worldwide, producers are concerned about increasing the total amount of protein in the seed without substantially lowering the amount of oil, another economically important product. Here we describe a transgenic soybean line with increased protein and protein/oil ratio, containing an average of 42.2% protein vs. 38.5% in controls and with a protein/oil ratio of 2.02 vs. 1.76 in controls over several generations of greenhouse growth. Other phenotypic data show that the seeds are heavier, although there are overall lower yields per plant. We postulate these effects result from insertion site mutagenesis by the transgenic construct. As this line never achieves homozygosity and appears to be embryo lethal when homozygous, one functional copy of the gene is most likely essential for normal seed development. Global transcript analyses using RNA-Seq for 88,000 gene models over two stages of cotyledon development revealed that more genes are over-expressed in the transgenic line including ribosomal protein related genes and those in the membrane protein and transporters families. Localization of the insertion site should reveal the genes and developmental program that has been perturbed by the transgenic construct, resulting in this economically interesting increase in protein and the protein/oil ratio

Antibody modulation of antigen presentation: positive and negative effects on presentation of the tetanus toxin antigen via the murine B cell isoform of FcgammaRII

Tetanus toxin has been a valuable model antigen to study the MHC class II-restricted antigen processing pathway and is also frequently used to provide T helper determinants in vaccine formulations. To date most basic studies on the processing of this antigen have utilized human T and B cell clones. As a first step towards extending studies on this antigen into the murine system we have generated a panel of T cell clones and mAb in H-2b and H-2d mice. We investigated the presentation of tetanus toxin C fragment (TTCF) by the murine B cell lines LB27.4 (H-2dxb), A20 (H-2d) and IIA1.6 (H-2d) and the extent to which this could be modulated by the addition of mAb. One mAb, 10G5, induced strikingly enhanced presentation of T cell determinants located in the N-terminal region of TTCF while other antibodies inhibited presentation of these and other epitopes. The enhancing effects of the 10G5 antibody were blocked by the anti-FcR antibody 2.4G2 and were not observed in the FcR-negative IIA1.6 cell line. Interestingly, both FcRIIB1 and FcRIIB2 isoforms of FcRII were able to restore antibody enhanced presentation in IIA1.6 cells but only if the cytoplasmic tails were intact. These results show that the B cell isoform of FcRII (FcRIIB1) can mediate capture and presentation of some antigen/antibody complexes and might play a role in BCR-independent antigen presentation in vivo

Soluble human leucocyte antigen-G molecules in peripheral blood haematopoietic stem cell transplantation: a specific role to prevent acute graft-versus-host disease and a link with regulatory T cells

Haematopoietic stem cell transplantation is often complicated by the life-threatening graft-versus-host disease (GVHD) which consists of an allogeneic reaction of the graft cells against the host organs. The aim of this study was to investigate the putative involvement of soluble human leucocyte antigen (sHLA) class I molecules, and particularly sHLA-G molecules, in the occurrence and/or prevention of acute GVHD (aGVHD) in allogeneic peripheral blood stem cell (PSC) transplantation. Whole sHLA class I molecules seem to be involved in aGVHD pathogenesis because detection of a high concentration of these molecules in the first month post allograft is correlated with aGVHD occurrence. Conversely, a high level of sHLA-G molecules before and after allograft could indicate good prognosis in PSC allograft transplantation. sHLA-G molecules seem to be involved in aGVHD prevention, not only because they are enriched in plasma of patients without aGVHD, but also because: (i) a positive correlation has been found between sHLA-G level and CD4+ CD25+ CD152+ natural regulatory T cell (Treg) frequency in the blood of transplanted patients; and (ii) the presence of CD4+ CD25+ CD152+ natural Treg is correlated with increased sHLA-G expression in in vitro mixed leucocyte reaction cultures. Altogether, these results support the immunomodulatory function of sHLA-G molecules that might create a regulatory network together with the natural Treg to foster the induction of a tolerogenic environment and improve PSC transplantation favourable outcome