This study examined whether long-term abacus-based mental calculation (AMC) training improved numerical processing efficiency and at what stage of information processing the effect appeard. Thirty-three children participated in the study and were randomly assigned to two groups at primary school entry, matched for age, gender and IQ. All children went through the same curriculum except that the abacus group received a 2-h/per week AMC training, while the control group did traditional numerical practice for a similar amount of time. After a 2-year training, they were tested with a numerical Stroop task. Electroencephalographic (EEG) and event related potential (ERP) recording techniques were used to monitor the temporal dynamics during the task. Children were required to determine the numerical magnitude (NC) (NC task) or the physical size (PC task) of two numbers presented simultaneously. In the NC task, the AMC group showed faster response times but similar accuracy compared to the control group. In the PC task, the two groups exhibited the same speed and accuracy. The saliency of numerical information relative to physical information was greater in AMC group. With regards to ERP results, the AMC group displayed congruity effects both in the earlier (N1) and later (N2 and LPC (late positive component) time domain, while the control group only displayed congruity effects for LPC. In the left parietal region, LPC amplitudes were larger for the AMC than the control group. Individual differences for LPC amplitudes over left parietal area showed a positive correlation with RTs in the NC task in both congruent and neutral conditions. After controlling for the N2 amplitude, this correlation also became significant in the incongruent condition. Our results suggest that AMC training can strengthen the relationship between symbolic representation and numerical magnitude so that numerical information processing becomes quicker and automatic in AMC children.

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1-4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyses the synthesis of cyclic GMP-AMP (cGAMP)9-12, which stimulates the induction of type I interferons through the STING-TBK1-IRF-3 signalling axis13-15. STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase8,16. The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK18,17-20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons21. However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNβ after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders.

Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.

The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.