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Background: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. Methods: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. Results: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. Conclusions: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders. Scheme depicting the possible mechanism by which DNase II deficiency induces cognitive impairment in mice. DNase II deficiency induces tau phosphorylation by regulating kinases CDK5 and CaMKII as well as phosphatase PP2A through accumulation of undigested damaged DNA in the cytoplasm of neurons. Then phosphorylated tau induces synaptic loss, neuroinflammation, and neuronal apoptosis, eventually rendering cognitive impairment in mice. [ABSTRACT FROM AUTHOR]

We studied the community of soil microorganisms, enzyme activity and soil nutrients under 11-, 20-, 34-and 47-year-old Larix kaempferi plantations in mountainous region of eastern Liaoning Province to discuss the soil biological properties of L. kaempferi plantations of different stand ages and their relationships with soil nutrients. The results showed that the indexes reflecting soil microorganisms, enzyme activity and soil nutrients of L. kaempferi plantations were the highest under the 11- or 47- year-old stand and the lowest in the 20- or 34-year-old stand. Soil productivity appeared in a decline trend with the increasing stand age, and the changes of soil microbial community structure and enzyme activity were responsive to soil degradation. The difference of fungi community was more noticeable than that of bacteria community among the plantations with different stand ages. The results of CCA showed soil nutrient and pH had no effect on seasonal difference of community structure, but had effects on community structure among different stand ages. The total N, organic carbon, C/ N, available nitrogen, exchangeable Mg2+ and pH had greater effects on bacteria community, while available P, total K and pH had greater effect on fungi community among different age forests. The main T-RFs of bacteria and fungi had higher correlation with N and P, and the fungi community had higher correlation with organic carbon and K than bacteria community. The microorganism community of the 11- and 47-year-old stands had greater correlation with soil nutrients and enzyme activity than that of 20- and 34-year-old stands. Consequently, soil organisms, in particular soil fungi, could be used to indicate soil degradation. [ABSTRACT FROM AUTHOR]

We studied the community of soil microorganisms, enzyme activity and soil nutrients under 11-, 20-, 34-and 47-year-old Larix kaempferi plantations in mountainous region of eastern Liaoning Province to discuss the soil biological properties of L. kaempferi plantations of different stand ages and their relationships with soil nutrients. The results showed that the indexes reflecting soil micro-organisms, enzyme activity and soil nutrients of L. kaempferi plantations were the highest under the 11- or 47-year-old stand and the lowest in the 20- or 34-year-old stand. Soil productivity appeared in a decline trend with the increasing stand age, and the changes of soil microbial community structure and enzyme activity were responsive to soil degradation. The difference of fungi community was more noticeable than that of bacteria community among the plantations with different stand ages. The results of CCA showed soil nutrient and pH had no effect on seasonal difference of community structure, but had effects on community, structure among different stand ages. The total N, organic carbon, C/N, available nitrogen, exchangeable Mg2+ and pH had greater effects on bacteria community, while available P, total K and pH had greater effect on fungi community among different age forests. The main T-RFs of bacteria and fungi had higher correlation with N and P, and the fungi community had higher correlation with organic carbon and K than bacteria community. The microor-ganism community of the 11- and 47-year-old stands had greater correlation with soil nutrients and enzyme activity than that of 20- and 34-year-old stands. Consequently, soil organisms, in particular soil fungi, could be used to indicate soil degradation.