NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

A comparative study of the water budgets of lawns under three management scenarios

The fate of irrigation in urban ecosystems is highly uncertain, due to uncertainties in urban ecohydrology. We compared irrigation rates, soil moisture, evapotranspiration (ET), stomatal conductance, and water budgets of landscape ecosystems managed with different turfgrass species and irrigation technologies. The “Typical” landscape had a cool-season fescue and was irrigated by an automatic timer. The “Alternative1” landscape had a warm-season paspalum and a “smart” soil moisture sensor-based irrigation system. The “Alternative2” landscape had a cool-season native sedge and a “smart” weather station-based drip irrigation system. ET was measured with a portable closed chamber and modeled using a Penman-Monteith approach, and the two methods agreed well. The water applied to the Alternative1 was 54 % less than the water applied to the Typical landscape, and the water applied to the Alternative2 was 24 % less. Soil moisture was similar in the Typical and Alternative2, while Alternative1 was drier in spring. The stomatal conductance of sedge was lower than the other two species, but its ET was not lower due to higher leaf area. Irrigation efficiencies (ET/applied irrigation) were 57 - 58&nbsp;%, 86 – 97&nbsp;%, and 78 - 80&nbsp;% for the Typical, Alternative1, and Alternative2 landscapes, respectively. Runoff was less than 2&nbsp;% in each landscape, and excess irrigation primarily drained below the root zone. Differences in irrigation efficiency between landscapes were due mainly to irrigation application, which varied more than species water use. Smart irrigation systems provided substantial water savings relative to a timer-based system, and prevented significant drainage losses. The utilization of smart sensors was more important than the choice of turfgrass species for irrigation efficiency