Evolution of Th2 responses : Characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Acknowledgements This research was funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference number HR09011) and contributing institutions.Peer reviewedPublisher PD

Cationic Amino Acid Transporter-2 Regulates Immunity by Modulating Arginase Activity

Cationic amino acid transporters (CAT) are important regulators of NOS2 and ARG1 activity because they regulate L-arginine availability. However, their role in the development of Th1/Th2 effector functions following infection has not been investigated. Here we dissect the function of CAT2 by studying two infectious disease models characterized by the development of polarized Th1 or Th2-type responses. We show that CAT2−/− mice are significantly more susceptible to the Th1-inducing pathogen Toxoplasma gondii. Although T. gondii infected CAT2−/− mice developed stronger IFN-γ responses, nitric oxide (NO) production was significantly impaired, which contributed to their enhanced susceptibility. In contrast, CAT2−/− mice infected with the Th2-inducing pathogen Schistosoma mansoni displayed no change in susceptibility to infection, although they succumbed to schistosomiasis at an accelerated rate. Granuloma formation and fibrosis, pathological features regulated by Th2 cytokines, were also exacerbated even though their Th2 response was reduced. Finally, while IL-13 blockade was highly efficacious in wild-type mice, the development of fibrosis in CAT2−/− mice was largely IL-13-independent. Instead, the exacerbated pathology was associated with increased arginase activity in fibroblasts and alternatively activated macrophages, both in vitro and in vivo. Thus, by controlling NOS2 and arginase activity, CAT2 functions as a potent regulator of immunity

Local structure adaptability through multi cations for oxygen redox accommodation in Li-Rich layered oxides

Stable lattice oxygen redox (l-OR) is the key enabler for achieving attainable high energy density in Li-rich layered oxide cathode materials for Li-ion batteries. However, the unique local structure response to oxygen redox in these materials, resulting in energy inefficiency and hysteresis, still remains elusive, preventing their potential applications. By combining the state-of-the-art neutron pair distribution function with crystal orbital overlap analysis, we directly observe the distinct local structure adaption originated from the potential O–O chemical bonds. The structure adaptability is optimized based on the nature of multi transition metals in our model compound Li1.2Ni0.13Mn0.54Co0.13O2, which accommodates the oxygen redox and at the same time preserves the global layered structure. These findings not only advance the understanding of l-OR, but also provide new perspectives in the rational design of high-energy-density cathode materials with reversible and stable l-OR

SELECTIVE MEASUREMENT OF α SMOOTH MUSCLE ACTIN: WHY β-ACTIN CAN NOT BE USED AS A HOUSEKEEPING GENE WHEN TISSUE FIBROSIS OCCURS

Abstract Background Prevalence of fibroproliferative diseases, including chronic kidney disease is rapidly increasing and has become a major public health problem worldwide. Fibroproliferative diseases are characterized by increased expression of α smooth muscle actin (α-SMA) that belongs to the family of the six conserved actin isoforms showing high degree homology. The aim of the present study was to develop real-time PCRs that clearly discriminate α-SMA and ß-actin from other actin isoforms. Results Real-time PCRs using self-designed mouse, human and rat specific α-SMA or ß-actin primer pairs resulted in the specific amplification of the artificial DNA templates corresponding to mouse, human or rat α-SMA or ß-actin, however ß-actin showed cross-reaction with the housekeeping γ-cyto-actin. We have shown that the use of improperly designed literary primer pairs significantly affects the results of PCRs measuring mRNA expression of α-SMA or ß-actin in the kidney of mice underwent UUO. Conclusion We developed a set of carefully designed primer pairs and PCR conditions to selectively determine the expression of mouse, human or rat α-SMA and ß-actin isoforms. We demonstrated the importance of primer specificity in experiments where the results are normalized to the expression of ß-actin especially when fibrosis and thus increased expression of α-SMA is occur

Nucleation of dislocations and their dynamics in layered oxide cathode materials during battery charging

Defects and their interactions in crystalline solids often underpin material properties and functionality as they are decisive for stability, result in enhanced diffusion, and act as a reservoir of vacancies. Recently, lithium-rich layered oxides have emerged among the leading candidates for the next-generation energy storage cathode material, delivering 50 % excess capacity over commercially used compounds. Oxygen-redox reactions are believed to be responsible for the excess capacity, however, voltage fading has prevented commercialization of these new materials. Despite extensive research the understanding of the mechanisms underpinning oxygen-redox reactions and voltage fade remain incomplete. Here, using operando three-dimensional Bragg coherent diffractive imaging, we directly observe nucleation of a mobile dislocation network in nanoparticles of lithium-rich layered oxide material. Surprisingly, we find that dislocations form more readily in the lithium-rich layered oxide material as compared with a conventional layered oxide material, suggesting a link between the defects and the anomalously high capacity in lithium-rich layered oxides. The formation of a network of partial dislocations dramatically alters the local lithium environment and contributes to the voltage fade. Based on our findings we design and demonstrate a method to recover the original high voltage functionality. Our findings reveal that the voltage fade in lithium-rich layered oxides is reversible and call for new paradigms for improved design of oxygen-redox active materials

Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans