40 research outputs found
The Deep Water Abundance on Jupiter: New Constraints from Thermochemical Kinetics and Diffusion Modeling
We have developed a one-dimensional thermochemical kinetics and diffusion
model for Jupiter's atmosphere that accurately describes the transition from
the thermochemical regime in the deep troposphere (where chemical equilibrium
is established) to the quenched regime in the upper troposphere (where chemical
equilibrium is disrupted). The model is used to calculate chemical abundances
of tropospheric constituents and to identify important chemical pathways for
CO-CH4 interconversion in hydrogen-dominated atmospheres. In particular, the
observed mole fraction and chemical behavior of CO is used to indirectly
constrain the Jovian water inventory. Our model can reproduce the observed
tropospheric CO abundance provided that the water mole fraction lies in the
range (0.25-6.0) x 10^-3 in Jupiter's deep troposphere, corresponding to an
enrichment of 0.3 to 7.3 times the protosolar abundance (assumed to be H2O/H2 =
9.61 x 10^-4). Our results suggest that Jupiter's oxygen enrichment is roughly
similar to that for carbon, nitrogen, and other heavy elements, and we conclude
that formation scenarios that require very large (>8 times solar) enrichments
in water can be ruled out. We also evaluate and refine the simple time-constant
arguments currently used to predict the quenched CO abundance on Jupiter, other
giant planets, and brown dwarfs.Comment: 42 pages, 7 figures, 4 tables, with note added in proof. Accepted for
publication in Icarus [in press
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
Ancient lineages of arbuscular mycorrhizal fungi provide little plant benefit
Open Access funding provided by Agroscope. This work was supported by the Swiss National Science Foundation SNSF, grant 130764 ("Antagonism in the mycorrhizal symbiosis-a search for mechanisms").Almost all land plants form symbiotic associations with arbuscular mycorrhizal fungi (AMF). Individual plants usually
are colonized by a wide range of phylogenetically diverse AMF species. The impact that different AMF taxa have on plant
growth is only partly understood. We screened 44 AMF isolates for their effect on growth promotion and nutrient uptake of
leek plants (Allium porrum), including isolates that have not been tested previously. In particular, we aimed to test weather
AMF lineages with an ancient evolutionary age differ from relatively recent lineages in their effects on leek plants. The AMF
isolates that were tested covered 18 species from all five AMF orders, eight families, and 13 genera. The experiment was
conducted in a greenhouse. A soilâsand mixture was used as substrate for the leek plants. Plant growth response to inoculation
with AMF varied from â 19 to 232% and depended on isolate, species, and family identity. Species from the ancient
families Archaeosporaceae and Paraglomeraceae tended to be less beneficial, in terms of stimulation plant growth and nutrient
uptake, than species of Glomeraceae, Entrophosporaceae, and Diversisporaceae, which are considered phylogenetically
more recent than those ancient families. Root colonization levels also depended on AMF family. This study indicates that
plant benefit in the symbiosis between plants and AMF is linked to fungal identity and phylogeny and it shows that there are
large differences in effectiveness of different AMF.AgroscopeSwiss National Science Foundation (SNSF) 13076
T Cell Activation and Proinflammatory Cytokine Production in Clinically Cured Tuberculosis Are Time-Dependent and Accompanied by Upregulation of IL-10.
Th1 cytokines are essential for the control of M. tuberculosis infection. The role of IL-10 in tuberculosis is controversial and there is an increasing body of evidence suggesting that the relationship between Th1 cytokines and IL-10 is not as antagonistic as it was first believed, and that these cytokines may complement each other in infectious diseases.The present study evaluated the activating capacity of CD4+ and CD8+ T cell repertoire in response to antigen stimulation through the expression of CD69 using Flow Cytometry, as well as the functionality of PBMCs by determining the cytokine profile in patients with active tuberculosis and in clinically cured patients after in vitro stimulation using ELISA. Treated patients were subdivided according to time after clinical cure (<12 months or >12 months post-treatment).We observed that T cell activation was higher in TB-treated patients, especially CD8+ T cell activation in TB-Treated >1 year. Th1 cytokines were significantly higher in TB-Treated, and the levels of IFN-γ and TNF-α increased continuously after clinical cure. Moreover, IL-10 production was significantly higher in cured patients and it was also enhanced in cured patients over time after treatment. Th17, Th2 and Th22 cytokines showed no statistically significant differences between Healthy Donors, Active-TB and TB-Treated.This study describes a scenario in which potentiation of CD4+ and CD8+ T cell activation and increased Th1 cytokine production are associated with the clinical cure of tuberculosis in the absence of significant changes in Th2 cytokine production and is accompanied by increased production of IL-10. In contrast to other infections with intracellular microorganisms, this response occurs later after the end of treatment
Ecological aspects of arbuscular mycorrhizal fungal communities in different habitat types of a Brazilian mountainous area
Th2, Th17 and Th22 cytokines in active and clinical cured tuberculosis.
<p>Production of IL-4, IL-13, IL-17, IL-6 and IL-22 by PBMCs from Healthy Donors, patients with active tuberculosis and clinically cured patients in unstimulated (medium only) and stimulated (4 ”g/mL <i>M. bovis</i> antigen) cultures. <b>A, B, C, E, F</b>. Comparison between patients with active tuberculosis and clinically cured patients (TB-treated). <b>D</b>. Comparison between active tuberculosis and different times after clinical cure (TB-treated<1 year and TB-treated>1 year). Horizontal lines represent the median, bars represent 25â75 percentiles, and vertical lines represent 10â90 percentiles. #p<0.05 in unstimulated versus stimulated cultures (4 ”g/mL <i>M. bovis</i> antigen), Wilcoxon test.</p
Correlation between IL-10 and Th1 cytokines in active and clinical cured tuberculosis.
<p>Correlation between IL-10 and IFN-γ or TNF-α levels produced by PBMCs from Healthy Donors (<b>A</b>), patients with active tuberculosis (<b>B</b>) and clinically cured patients (<b>C</b>) in stimulated cultures (4 ”g/mL <i>M. bovis</i> antigen). Values of <i>p</i> and <i>r</i> determined using Spearman's correlation test.</p