Epicutaneous Application of CpG Oligodeoxynucleotides with Peptide or Protein Antigen Promotes the Generation of CTL

Immunostimulatory oligodeoxynucleotides (ODN) are effective adjuvants in the induction of humoral and cellular immune responses when administered parenterally with antigen. The skin has recently become a target organ for the design of non-invasive vaccine technologies. Using ovalbumin (OVA) as a model antigen, we demonstrate that the application of ODN sequences to tape-stripped skin promotes the induction of potent cytotoxic T lymphocyte (CTL) responses to co-administered peptide. Induction of peptide-specific CTL required the presence of CpG motifs within the ODN. CTL afforded tumor protection against a tumor expressing an immunodominant OVA CTL epitope. CTL could also be induced to whole protein administered onto the skin. Differential CpG sequence activity was noted with respect to the induction of CTL to epicutaneous protein with an ODN sequence containing a poly-G motif having an optimal effect. Peptide-specific CTL could be detected in the peripheral blood as early as 6 d after a single immunization. These results highlight the potential of the bare skin as a route for vaccine development and indicate an important role for immunostimulatory ODN as adjuvants to generate functional CTL with the help of the skin immune system

Optical transition radiation in fused quartz under external acoustic field

In the present paper we have investigated the optical transition radiation in a plate excited by a longitudinal acoustic wave. The spectral-angular density of the radiated energy is calculated. The numerical examples are given for a plate of fused quartz. These results show that the acoustic waves allow to control the parameters of the radiation. In particular, new resonance peaks appear in the spectral distribution of the radiation intensity. The height of the peaks can be tuned by choosing the parameters of the acoustic wave

Experimental investigation of optical transition radiation in amorphous quartz

Optical transition radiation (OTR) in amorphous quartz is investigated experimentally for electrons with energies 7.5MeV. It is shown that the Cherenkov radiation and OTR can be separated at specific conditions. The linear polarization of OTR is investigated and it is shown that the polarization is radial. The results of measurements for the spectral distribution of OTR have shown the maximum intensity of radiation at the wavelengths in the range 320–500 nm

Structure and evolution of the Gulf of Lions: The Sardinia seismic experiment and the GOLD (Gulf of Lions Drilling) project

International audienceThe study of the deep structure and evolution of passive continental margins is important for the understanding of rifting processes and the formation of associated sedimentary basins. Since the classical models of McKenzie (1978) and Wernicke (1985), understanding how passive continental margins form, that is to say mainly the way that continental lithosphere is thinned leading to subsidence, remains one of the main challenges in the Earth sciences. Many recent observations and discoveries have modified our basic views of margin formation. The conservational models paradigm (i.e., simple shear, pure shear, or polyphase models), which exclude exchanges between lower continental crust and upper mantle and which are usually proposed to explain lithospheric stretching and consequent crustal thinning of passive continental margins, fail to completely explain all these observations. Furthermore, these models imply a large amount of horizontal movement, movements not observed in the field. In consequence, new concepts need to be built and tested

Coal in the 21st Century: a climate of change and uncertainty

Coal presents a particular set of challenges when balancing energy policy goals. Despite presenting viable solutions to the problems of energy security and global energy poverty, coal struggles, given its greenhouse-gas drawbacks, in a world of increasingly harmful climate change. Notwithstanding the harm caused to the environment, coal remains an expanding low-price route to meeting local energy needs. It is forecasted to remain a major global resource for the foreseeable future. In the short term it is predicted to have a 26% share of the global energy mix. Recent years have witnessed severe deviations from previously stable trends in coal markets and policy dynamics. According to the predictions by the International Energy Agency (IEA), a variety of factors ranging from the planned phase-out of coal in countries such as Denmark, France and the UK, to changes in policy in China and import-dependency in India, and demand drop in the US have together resulted in the largest decline in coal production in 2015 since 1971 (IEA, Coal Information, 2016). This paper seeks to outline basic coal facts, recent market trends and directions globally and provides an overview of issues shaping the future of coal in the twenty-first century. This paper seeks to outline basic coal facts, recent market trends and directions globally and provide an overview of issues shaping the future of coal in the 21st century

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts

Background: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO). Methods: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1. Results: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro. Conclusions: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth

MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified <it>MDM2 </it>gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy.</p> <p>Methods</p> <p>A panel of sarcoma cell lines with different <it>TP53 </it>and <it>MDM2 </it>status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined.</p> <p>Results</p> <p>Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type <it>TP53 </it>and amplified <it>MDM2</it>, or with Methotrexate in both <it>MDM2 </it>normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated <it>TP53</it>, but inhibited the effect of Methotrexate.</p> <p>Conclusion</p> <p>The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.</p

A review of the renal system and diurnal variations of renal activity in livestock

Kidneys are the main organs regulating water-electrolyte homeostasis in the body. They are responsible for maintaining the total volume of water and its distribution in particular water spaces, for electrolyte composition of systemic fluids and also for maintaining acid-base balance. These functions are performed by the plasma filtration process in renal glomeruli and the processes of active absorption and secretion in renal tubules, all adjusted to an 'activity-rest' rhythm. These diurnal changes are influenced by a 24-hour cycle of activity of hormones engaged in the regulation of renal activity. Studies on spontaneous rhythms of renal activity have been carried out mainly on humans and laboratory animals, but few studies have been carried out on livestock animals. Moreover, those results cover only some aspects of renal physiology. This review gives an overview of current knowledge concerning renal function and diurnal variations of some renal activity parameters in livestock, providing greater understanding of general chronobiological processes in mammals. Detailed knowledge of these rhythms is useful for clinical, practical and pharmacological purposes, as well as studies on their physical performance