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To spatially control biochemical functions at specific sites within a genome, we have engineered a synthetic switch that activates when bound to its DNA target site. The system uses two CRISPR–Cas complexes to colocalize components of a de novo-designed protein switch (Co-LOCKR) to adjacent sites in the genome. Colocalization triggers a conformational change in the switch from an inactive closed state to an active open state with an exposed functional peptide. We prototype the system in yeast and demonstrate that DNA binding triggers activation of the switch, recruitment of a transcription factor, and expression of a downstream reporter gene. This DNA-triggered Co-LOCKR switch provides a platform to engineer sophisticated functions that should only be executed at a specific target site within the genome, with potential applications in a wide range of synthetic systems including epigenetic regulation, imaging, and genetic logic circuits.

significant intergroup differences were observed in the postoperative preservation ratio of eGFR at 6 or 12 months of follow-up (full clamping 94.0% vs. selective clamping 92.7%, p[0.509; and full clamping 92.0% vs. selective clamping 91.6%, p[0.476, respectively).CONCLUSIONS: Selective clamping resulted in higher EBL rates than did full clamping in RAPN. However, selective clamping provided no renal functional advantage over full clamping in our propensity score-matched cohort.

This article revisits four online news business models, first documented in 1997, to discuss current worldwide newspaper website trends and new research data on Australian newspaper websites. The data are from a survey of Australian newspapers and their websites, and show that the Australian experience mirrors international experience in terms of the growth of newspapers online and their lack of profitability. The survey shows that, while there is international evidence that providing news content online reduces offline newspaper subscriptions, a third of the newspapers studied registered circulation increases after setting up their websites. While there is international evidence that generating revenue through online advertising is difficult, for nearly half of the newspapers studied, overall advertising revenue increased after setting up their websites. The survey also found that, while newspaper publishers worldwide continue to rely mainly on the subscription and advertising business models to generate revenue online, there is evidence that Australian newspapers are forming online alliances with other media and non-media businesses to facilitate their online business activities.

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