Targeting the mosquito prefoldin–chaperonin complex blocks Plasmodium transmission
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Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice
Gene expression of Plasmodium falciparum (Pf) liver-stage (LS) parasites has remained poorly characterized, although they are major vaccine and drug targets. Using a human liver-chimaeric mouse model and a fluorescent parasite line (PfNF54CSPGFP), we isolated PfLS and performed transcriptomics on key LS developmental phases. We linked clustered gene expression to ApiAP2, a major family of transcription factors that regulate the parasite life cycle. This provided insights into transcriptional regulation of LS infection and expression of essential LS metabolic and biosynthetic pathways. We observed expression of antigenically variant PfEMP1 proteins and the major Pf protein export machine PTEX and identified protein candidates that might be exported by LS parasites. Comparing Pf and P. vivax LS transcriptomes, we uncovered differences in their expression of sexual commitment factors. This data will aid LS research and vaccine and drug target identification for prevention of malaria infection.
Grid-enhancing technologies for clean energy systems
Renewable energy source integration into energy systems can contribute to transmission congestion, which requires time-consuming and capital-intensive upgrades to address. Grid-enhancing technologies (GETs) can increase the capacity of grids with minimal investment, preventing congestion and curtailment of renewable energy. In this Review, we discuss the principles and uses of GETs, which use software and/or hardware to interpret real-time conditions to better use the existing capacity of grid assets. GETs include dynamic line ratings, dynamic transformer ratings, power flow controls, topology optimization, advanced conductor technologies, energy storage systems, and demand response. These GETs can enhance system performance individually, but the deployment of multiple GETs together would greatly increase their effect on the grid capacity and stability by removing multiple capacity bottlenecks in parallel. Infrastructure for real-time data acquisition, transmission and analysis is key to successfully deploying GETs but requires further development and commercialization for broader deployment.
CRISPRi-ART enables functional genomics of diverse bacteriophages using RNA-binding dCas13d
Bacteriophages constitute one of the largest reservoirs of genes of unknown function in the biosphere. Even in well-characterized phages, the functions of most genes remain unknown. Experimental approaches to study phage gene fitness and function at genome scale are lacking, partly because phages subvert many modern functional genomics tools. Here we leverage RNA-targeting dCas13d to selectively interfere with protein translation and to measure phage gene fitness at a transcriptome-wide scale. We find CRISPR Interference through Antisense RNA-Targeting (CRISPRi-ART) to be effective across phage phylogeny, from model ssRNA, ssDNA and dsDNA phages to nucleus-forming jumbo phages. Using CRISPRi-ART, we determine a conserved role of diverse rII homologues in subverting phage Lambda RexAB-mediated immunity to superinfection and identify genes critical for phage fitness. CRISPRi-ART establishes a broad-spectrum phage functional genomics platform, revealing more than 90 previously unknown genes important for phage fitness.
Pathogens and planetary change
Emerging infectious diseases, biodiversity loss, and anthropogenic environmental change are interconnected crises with massive social and ecological costs. In this Review, we discuss how pathogens and parasites are responding to global change, and the implications for pandemic prevention and biodiversity conservation. Ecological and evolutionary principles help to explain why both pandemics and wildlife die-offs are becoming more common; why land-use change and biodiversity loss are often followed by an increase in zoonotic and vector-borne diseases; and why some species, such as bats, host so many emerging pathogens. To prevent the next pandemic, scientists should focus on monitoring and limiting the spread of a handful of high-risk viruses, especially at key interfaces such as farms and live-animal markets. But to address the much broader set of infectious disease risks associated with the Anthropocene, decision-makers will need to develop comprehensive strategies that include pathogen surveillance across species and ecosystems; conservation-based interventions to reduce human–animal contact and protect wildlife health; health system strengthening; and global improvements in epidemic preparedness and response. Scientists can contribute to these efforts by filling global gaps in disease data, and by expanding the evidence base for disease–driver relationships and ecological interventions.
Simultaneous tACS-fMRI reveals state- and frequency-specific modulation of hippocampal-cortical functional connectivity
Non-invasive indirect hippocampal-targeted stimulation is of broad scientific and clinical interest. Transcranial alternating current stimulation (tACS) is appealing because it allows oscillatory stimulation to study hippocampal theta (3–8 Hz) activity. We found that tACS administered during functional magnetic resonance imaging yielded a frequency-, mental state- and topologically-specific effect of theta stimulation (but not other frequencies) enhancing right (but not left) hippocampal-cortical connectivity during resting blocks but not during task blocks. Control analyses showed that this effect was not due to possible stimulation-induced changes in signal quality or head movement. Our findings are promising for targeted network modulations of deep brain structures for research and clinical intervention.
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