•OH Inactivation of Cyanobacterial Blooms and Degradation of Toxins in Drinking Water Treatment System.

Cyanobacterial blooms continue to serve as one of the most serious global issues threatening water supply and human health. During cyanobacterial bloom season, a large •OH-yield equipment was developed and installed after coagulation settling in a 12000 ton/day drinking water treatment system in Xiamen, China. An •OH concentration of 7.76∼57.8 µmol/L was formed by using the oxygen activated species generated by strong ionisation discharge combining with the effect of water jet cavitation. •OH pre-treatment at a dose of 1.0 mg/L inactivated cyanobacterial blooms in the process of conveying bloom water within only 20s, which were then removed by sand filtration. Under SEM observation, dominant Microcystis sp. colonies connected by mucilage were dispersed into individuals that still retained the cell integrity, indicating no release of intracellular organic matter (IOM). According to a flow cytometry analysis, the main cause of •OH inactivation was the breakage of DNA strands. Meanwhile, the •OH-mineralized microcystin-LR was by breaking the C=C conjugated diene bond and crucial opening the persistent benzene ring to carboxylic acid m/z 158.0. During •OH pre-treatment of 1.0 mg/L and NaClO disinfection of 0.5 mg/L, all water quality indexes and disinfection by-product (DBP) contents complied with the Chinese Sanitary Standards for Drinking Water. Therefore, the •OH based on the strong ionisation discharge showed great prospect for large-scale drinking water treatment in the removal of cyanobacterial blooms while retaining cell integrity as well as the degradation of toxins.

TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys.

Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.

Spatial and temporal profile of haloperidol-induced immediate-early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine-sensitized rats.

To determine if D(2) dopamine receptor-mediated nuclear signaling is altered during the development of amphetamine sensitization, we examined the expression of immediate-early gene (IEG) products, Fos, Jun, and Fos-related antigen (FRA), in both controls and amphetamine-sensitized rats after a challenge with the D(2) antagonist haloperidol. When chronic saline- or amphetamine (5 mg/kg, i.p. for 14 days)-treated rats were challenged with 2 mg/kg haloperidol at withdrawal day 3 (w3), more 35-kDa FRA was induced in the ventral striatum of the control group than in the amphetamine-treated rats. In contrast, more Jun and 35-kDa FRA were expressed in the ventral striatum of the amphetamine-treated group than in the controls when haloperidol was given at w10. Topographical analyses indicate that the decrease in FRA immunoreactive neuronal density in amphetamine-treated rats at w3 were located in the dorsolateral caudate/putamen and the nucleus accumbens shell and core subregions. Conversely, the increase in Jun-immunoreactive neurons in amphetamine-treated rats at w10 was observed in the dorsolateral caudate/putamen; in the case of the FRAs, the increase was observed in the nucleus accumbens shell. In addition, the time-dependent profile of IEG expression paralleled the activation of an upstream regulator, cAMP-response element binding protein, in the ventral striatum after haloperidol treatment. These neurochemical changes may be associated with behavioral plasticity, since amphetamine-treated rats displayed a lower amount of locomotor activity when exposed to a novel environment at w3, but had recovered at w10. Overall, the current study reveals that there is a distinct temporal and spatial profile of haloperidol-induced IEG expression and/or CREB phosphorylation in amphetamine-treated rats, suggesting that there is a critical transition between the early and late withdrawal periods.