Overproduction of Neurons Is Correlated with Enhanced Cortical Ensembles and Increased Perceptual Discrimination

Brains vary greatly in neuronal number and density, even across individuals within the same species, yet it remains unclear whether such variation leads to differences in brain function or behavior. By imaging cortical activity of a mouse model in which neuronal production is moderately enhanced in utero, we find that animals with more cortical neurons also develop enhanced functional correlations and more distinct neuronal ensembles in primary visual cortex. These mice also have sharper orientation discrimination in their visual behavior. These results unveil a correlation between neuronal ensembles and behavior and suggest that neuronal number is linked to functional modularity and perceptual discrimination of visual cortex. By experimentally linking differences in neuronal number and behavior, our findings could help explain how evolutionary and developmental variability of individual and species brain size may lead to perceptual and cognitive differences

Why does the apparent mass of a coronal mass ejection increase?

Mass is one of the most fundamental parameters characterizing the dynamics of a coronal mass ejection (CME). It has been found that CME apparent mass measured from the brightness enhancement in coronagraph images shows an increasing trend during its evolution in the corona. However, the physics behind it is not clear. Does the apparent mass gain come from the mass outflow from the dimming regions in the low corona, or from the pileup of the solar wind plasma around the CME when it propagates outwards from the Sun? We analyzed the mass evolution of six CME events. Their mass can increase by a factor of 1.6 to 3.2 from 4 to 15 Rs in the field of view (FOV) of the coronagraph on board the Solar Terrestrial Relations Observatory (STEREO). Over the distance about 7 to 15 Rs, where the coronagraph occulting effect can be negligible, the mass can increase by a factor of 1.3 to 1.7. We adopted the `snow-plough' model to calculate the mass contribution of the piled-up solar wind in the height range from about 7 to 15 Rs. For 2/3 of the events, the solar wind pileup is not sufficient to explain the measured mass increase. In the height range from about 7 to 15 Rs, the ratio of the modeled to the measured mass increase is roughly larger than 0.55. Although the ratios are believed to be overestimated, the result gives evidence that the solar wind pileup probably makes a non-negligible contribution to the mass increase. It is not clear yet whether the solar wind pileup is a major contributor to the final mass derived from coronagraph observations. However, our study suggests that the solar wind pileup plays increasingly important role in the mass increase as a CME moves further away from the Sun.Comment: 27 pages, 2 tables, 9 figures, accepted by Ap

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

Strategies on Nanodiagnostics and Nanotherapies of the Three Common Cancers

The emergence of nanomedicine has enriched the knowledge and strategies of treating diseases, and especially some incurable diseases, such as cancers, acquired immune deficiency syndrome (AIDS), and neurodegenerative diseases. The application of nanoparticles in medicine is in the core of nanomedicine. Nanoparticles can be used in drug delivery for improving the uptake of poorly soluble drugs, targeted delivery to a specific site, and drug bioavailability. Early diagnosis of and targeted therapies for cancers can significantly improve patients’ quality of life and extend patients’ lives. The advantages of nanoparticles have given them a progressively important role in the nanodiagnosis and nanotherapy of common cancers. To provide a reference for the further application of nanoparticles, this review focuses on the recent development and application of nanoparticles in the early diagnosis and treatment of the three common cancers (lung cancer, liver cancer, and breast cancer) by using quantum dots, magnetic nanoparticles, and gold nanoparticles