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Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhances regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma., The Atr-Check1 pathway is involved in cell cycle and the DNA damage response. Here, the authors show that the Atr-Check1 pathway can inhibit axon regeneration in response to Piezo-mediated mechanosensation, affecting functional recovery.

The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.

Ferret badger (FB) rabies viruses JX09-17(fb), JX09-18 and JX10-37 were isolated from three different regions in Jiangxi province, China, in 2009 and 2010. The complete nucleotide sequence identity between these three isolates was 87-93 %. Compared with the other Chinese rabies virus isolates and vaccine strains, 101 substitutions (53 in JX10-37, 23 in JX09-17(fb) and 25 in JX09-18) in the five structural proteins were observed, and 47 of these substitutions (27 in JX10-37, 14 in JX09-17(fb) and 6 in JX09-18) were unique among lyssaviruses. Amino acid substitutions of S231 and Q333 were noted respectively in the G protein antigenic site I of JX10-37 and site III in JX09-17(fb). Phylogenetic analysis showed that JX09-17(fb) is rooted within the China I lineage, JX09-18 is in China II, and JX10-37 is independent. Evolutionary analysis and comparative sequence data indicate that isolate JX10-37 is a variant virus that diverged from canine rabies viruses around 1933 (range 1886-1963).

A canine rabies virus, Shaanxi-HZ-6, was isolated in Shaanxi Province, China, in 2009. Its genome has been completely sequenced and found to be closely related to the China I rabies virus strains widely circulating in China. The genomic length was 11,923 base pairs, and the overall organization of the genome was similar to that of other rabies virus isolates. Compared with isolates CQ92 and J, 84 amino acid substitutions (7 in the N gene, 15 in P, 6 in M, 25 in G, 31 in L) were observed in strain Shaanxi-HZ-6. Amino acid substitutions of R264H and V332I were noted in the G protein antigenic site I and site III, respectively. Residue 333 of the G protein, which is considered to be associated with pathogenicity, was Arg in Shaanxi-HZ-6. These and other substitutions may help provide an explanation why the China I lineage strain maintains its prevalence in China.

Background Tick-borne rickettsioses are considered important emerging zoonoses worldwide, but their etiological agents, rickettsiae, remain poorly characterized in northeastern China, where many human cases have been reported during the past several years. Here, we determined the characteristics of Rickettsia spp. infections in ticks in this area. Methods Ticks were collected by flagging vegetation from Jilin and Heilongjiang provinces of northeastern China followed by morphological identification. The presence of Rickettsia spp. in ticks was detected by PCR targeting the 23S-5S ribosomal RNA intergenic spacer, citrate synthase (gltA) gene, and 190-kDa outer membrane protein gene (ompA). The newly-generated sequences were subjected to phylogenetic analysis using the software MEGA 6.0. Results The overall infection rate of Rickettsia spp. was 6.12 %. Phylogenetic analyses based on the partial gltA and ompA genes demonstrated that rickettsiae detected in the ticks belong to four species, including “Candidatus Rickettsia tarasevichiae”, Rickettsia heilongjiangensis, Rickettsia raoultii, and a potential new species isolate. The associated tick species were also identified, i.e. Dermacentor nuttalli and Dermacentor silvarum for R. raoultii, Haemaphysalis concinna and Haemaphysalis longicornis for R. heilongjiangensis, and Ixodes persulcatus for “Ca. R. tarasevichiae”. All Rickettsia spp. showed significantly high infection rates in ticks from Heilongjiang when compared to Jilin Province. Conclusion Rickettsia heilongjiangensis, R. raoultii and “Ca. R. tarasevichiae” are widely present in the associated ticks in northeastern China, but more prevalent in Heilongjiang Province. The data of this study increase the information on the distribution of Rickettsia spp. in northeastern China, which have important public health implications in consideration of their recent association with human diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1764-2) contains supplementary material, which is available to authorized users.