Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation.

Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response

Simple synthesis of karahanaenone

1169-117

Cytotoxic T-cells mediate exercise-induced reductions in tumor growth

Funder: Vetenskapsrådet; FundRef: http://dx.doi.org/10.13039/501100004359Funder: Cancerfonden; FundRef: http://dx.doi.org/10.13039/501100002794Funder: Barncancerfonden; FundRef: http://dx.doi.org/10.13039/501100006313Funder: Svenska Läkaresällskapet; FundRef: http://dx.doi.org/10.13039/501100007687Funder: Cancer Research UK; FundRef: http://dx.doi.org/10.13039/501100000289Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effects of exercise on tumor progression are unclear, as are the cellular actors involved. We show here that in mice, exercise-induced reduction in tumor growth is dependent on CD8+ T cells, and that metabolites produced in skeletal muscle and excreted into plasma at high levels during exertion in both mice and humans enhance the effector profile of CD8+ T-cells. We found that activated murine CD8+ T cells alter their central carbon metabolism in response to exertion in vivo, and that immune cells from trained mice are more potent antitumor effector cells when transferred into tumor-bearing untrained animals. These data demonstrate that CD8+ T cells are metabolically altered by exercise in a manner that acts to improve their antitumoral efficacy

Glycolytic Response to Inflammation Over Time: Role of Myeloid HIF-1alpha

The in vivo response to lipopolysaccharide (LPS) occurs rapidly and has profound physiological and metabolic effects. The hypoxia inducible (HIF) transcription factor is an intrinsic and essential part of inflammation, and is induced by LPS. To determine the importance of the HIF response in regulating metabolism following an LPS response, glucose uptake was quantified in a time dependent manner in mice lacking HIF-1α in myeloid cells. We found that deletion of HIF-1α has an acute protective effect on LPS-induced hypoglycemia. Furthermore, reduced glucose uptake was observed in the heart and brown fat, in a time dependent manner, following loss of HIF-1α. To determine the physiological significance of these findings, cardiovascular, body temperature, and blood pressure changes were subsequently quantified in real time using radiotelemetry measurements. These studies reveal the temporal aspects of HIF-1α as a regulator of the metabolic response to acute LPS-induced inflammation

Pt-Sn/C as a possible methanol-tolerant cathode catalyst for DMFC

An effective method was developed for preparing highly dispersed nano-sized Pt–Sn/C electrocatalyst synthesised by a modified polyol reduction method. From XRD patterns, the Pt–Sn/C peaks shifted slightly to lower 2θ angles when compared with commercial Pt/C catalyst, suggesting that Sn formed alloy with Pt. Based on HR-TEM images, the Pt–Sn/C nanoparticles showed small particle sizes and well dispersed onto the carbon support with a narrow particle distribution. The methanol oxidation reaction on the as-prepared Pt–Sn/C catalyst appeared at lower currents (+7.08 mA at +480 mV vs. Ag/AgCl) compared to the commercial Pt/C (+8.25 mA at +480 mV vs. Ag/AgCl) suggesting that the Pt–Sn/C catalyst has ‘methanol tolerance capabilities’. Pt–Sn/C HA Slurry pH3 catalysts showed better activity towards the oxygen-reduction reaction (ORR) than commercial Pt/C which could be attributed to smaller particle sizes. In our study, the Pt–Sn/C catalyst appears to be a promising methanol-tolerant catalyst with activity towards the ORR in the DMFC.Web of Scienc

Nanoparticulate TiO2-promoted PtRu/C catalyst for methanol oxidation: TiO2 nanoparticles promoted PtRu/C catalyst for MOR

To improve the electrocatalytic properties of PtRu/C in methanol electrooxidation, nanoparticulate TiO2-promoted PtRu/C catalysts were prepared by directly mixing TiO2 nanoparticles with PtRu/C. Using cyclic voltammetry, it was found that the addition of 10 wt% TiO2 nanoparticles can effectively improve the electrocatalytic activity and stability of the catalyst during methanol electro-oxidation. The value of the apparent activation energy (Ea) for TiO2-PtRu/C was lower than that for pure PtRu/C at a potential range from 0.45 to 0.60 V. A synergistic effect between PtRu and TiO2 nanoparticles is likely to facilitate the removal of CO-like intermediates from the surface of PtRu catalyst and reduce the poisoning of the PtRu catalysts during methanol electrooxidation. Therefore, we conclude that the direct introduction of TiO2 nanoparticles into PtRu/ C catalysts offers an improved facile method to enhance the electrocatalytic performance of PtRu/C catalyst in methanol electrooxidation.Web of Scienc

Resveratrol: A Multifunctional Compound Improving Endothelial Function: Editorial to: “Resveratrol Supplementation Gender Independently Improves Endothelial Reactivity and Suppresses Superoxide Production in Healthy Rats” by S. Soylemez et al.

The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression and activity of NADPH oxidases, resveratrol inhibits superoxide-mediated NO inactivation. Some resveratrol effects are mediated by sirtuin 1 (SIRT1) or estrogen receptors, respectively

Insertion of Horizontally Transferred Genes within Conserved Syntenic Regions of Yeast Genomes

Horizontal gene transfer has been occasionally mentioned in eukaryotic genomes, but such events appear much less numerous than in prokaryotes, where they play important functional and evolutionary roles. In yeasts, few independent cases have been described, some of which corresponding to major metabolic functions, but no systematic screening of horizontally transferred genes has been attempted so far. Taking advantage of the synteny conservation among five newly sequenced and annotated genomes of Saccharomycetaceae, we carried out a systematic search for HGT candidates amidst genes present in only one species within conserved synteny blocks. Out of 255 species-specific genes, we discovered 11 candidates for HGT, based on their similarity with bacterial proteins and on reconstructed phylogenies. This corresponds to a minimum of six transfer events because some horizontally acquired genes appear to rapidly duplicate in yeast genomes (e.g. YwqG genes in Kluyveromyces thermotolerans and serine recombinase genes of the IS607 family in Saccharomyces kluyveri). We show that the resulting copies are submitted to a strong functional selective pressure. The mechanisms of DNA transfer and integration are discussed, in relation with the generally small size of HGT candidates. Our results on a limited set of species expand by 50% the number of previously published HGT cases in hemiascomycetous yeasts, suggesting that this type of event is more frequent than usually thought. Our restrictive method does not exclude the possibility that additional HGT events exist. Actually, ancestral events common to several yeast species must have been overlooked, and the absence of homologs in present databases leaves open the question of the origin of the 244 remaining species-specific genes inserted within conserved synteny blocks