Nitric oxide (NO) is a ubiquitous gas with free radical groups that is soluble in water, and which is involved in numerous physiological functions including inflammatory and immune responses. However, the role of NO in tumor biology is controversial and misunderstood. NO has been shown to have both anti-cancer and carcinogenic effects, which are dependent on the time, location, and concentration of NO. This duality presents a double challenge to determine the net impact of NO on cancer and to define the therapeutic role of NO-centered anti-cancer strategies. Nevertheless, it is believed that a comprehensive and dynamic understanding of the cascade of molecular and cellular events underlying tumor biology that are affected by NO will allow researchers to exploit the potential anti-tumor properties of drugs that interfere with NO metabolism.

We investigated if elevated CO2 could alleviate the negative effect of high temperature on fruit yield of strawberry (Fragaria × ananassa Duch. cv. Toyonoka) at different levels of nitrogen and also tested the combined effects of CO2, temperature and nitrogen on fruit quality of plants cultivated in controlled growth chambers. Results show that elevated CO2 and high temperature caused a further 12% and 35% decrease in fruit yield at low and high nitrogen, respectively. The fewer inflorescences and smaller umbel size during flower induction caused the reduction of fruit yield at elevated CO2 and high temperature. Interestingly, nitrogen application has no beneficial effect on fruit yield, and this may be because of decreased sucrose export to the shoot apical meristem at floral transition. Moreover, elevated CO2 increased the levels of dry matter-content, fructose, glucose, total sugar and sweetness index per dry matter, but decreased fruit nitrogen content, total antioxidant capacity and all antioxidant compounds per dry matter in strawberry fruit. The reduction of fruit nitrogen content and antioxidant activity was mainly caused by the dilution effect of accumulated non-structural carbohydrates sourced from the increased net photosynthetic rate at elevated CO2. Thus, the quality of strawberry fruit would increase because of the increased sweetness and the similar amount of fruit nitrogen content, antioxidant activity per fresh matter at elevated CO2. Overall, we found that elevated CO2 improved the production of strawberry (including yield and quality) at low temperature, but decreased it at high temperature. The dramatic fluctuation in strawberry yield between low and high temperature at elevated CO2 implies that more attention should be paid to the process of flower induction under climate change, especially in fruits that require winter chilling for reproductive growth.

It was reported that TNF receptor type II signaling, which has the capacity to stimulate CD4 + forkhead box P3 + (Foxp3 + ) regulatory T cells (Tregs), activated the noncanonical NF-kB pathway in an IKKa-dependent manner. Therefore, we studied the role of IKKa in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKKa in CD4 cells (Ikka f/f :CD4.Cre) that showed a >60% reduction in the number of Tregs in the thymus and peripheral lymphoid tissues, whereas the number of Foxp3 2 effector T cells (Teffs) remained at a normal level. The function of Tregs deficient in IKKa was examined using Rag1 2/2 mice cotransferred with naive CD4 cells (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of WT nCD4s, IKKa-deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1 2/2 mice. Furthermore, nCD4s deficient in IKKa also failed to reconstitute Rag1 2/2 mice and were defective in proliferative responses in vitro and in vivo. Thus, our study reveals a novel role of IKKa in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKKa may be exploited as therapeutic strategies in the treatment of major human diseases.-Chen, X., Willette-Brown, J., Wu, X., Hu, Y., Howard, O. M. Z., Hu, Y., Oppenheim, J. J. IKKa is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells. FASEB J. 29, 443-454 (2015). www.fasebj.org