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Ando, H.

Publications and source records attributed to Ando, H..

2 recordsLinked to original sources

Effective connectivity during autobiographical memory search

Autobiographical memory (AM) retrieval is known to recruit a widely distributed network of brain regions but much less is known regarding how these regions interact during the various phases that presumably take place during episodic memory retrieval in general and AM retrieval in particular. Here, we used dynamic causal modeling (DCM) to examine effective connectivity during cued AM search in a sub-network consisting of six major regions within this large network. Functional MRI data was acquired while participants were visually presented verbal cues describing common life events and requested to search for a personal memory that could be associated with each cue. We examined directed couplings between the ventromedial (vmPFC), dorsomedial (dmPFC) and dorsolateral prefrontal cortices (dlPFC), hippocampus, angular gyrus and a region in the posterior midline cortex (RSC/PCC/Prec), all located in the left hemisphere. Results indicated that during AM search, the vmPFC, dlPFC and RSC/PCC/Prec acted as primary drivers of activity in the rest of the network. Moreover, when AM search was completed successfully (Hits), an up-modulation of the effective connectivity of the hippocampus in the vmPFC and angular gyrus was observed. In the same way, there was an increase in the influence of the RSC/PCC/Prec in the activity of the dlPFC and dmPFC. Furthermore, during Hits the angular gyrus showed to have an inhibitory effect in all other nodes of the network. These results are consistent with the notion that midline cortical regions are crucial in supporting the retrieval of AMs, and highlight the interplay between the vmPFC and the RSC/PCC/Prec and the dlPFC during AM search.

neuroscience

Engineering Phage Host-Range and Suppressing Bacterial Resistance Through Phage Tail Fiber Mutagenesis

The rapid emergence of antibiotic-resistant infections is prompting increased interest in phage-based antimicrobials. However, acquisition of resistance by bacteria is a major issue in the successful development of phage therapies. Through natural evolution and structural modeling, we identified host-range determining regions (HRDR) in the T3 phage tail fiber protein and developed a high-throughput strategy to genetically engineer these regions through site-directed mutagenesis. Inspired by antibody specificity engineering, this approach generates deep functional diversity (>107 different members), while minimizing disruptions to the overall protein structure, resulting in synthetic \"phagebodies\". We showed that mutating HRDRs yields phagebodies with altered host-ranges. Select phagebodies enable long-term suppression of bacterial growth by preventing the appearance of resistance in vitro and are functional in vivo using a mouse skin infection model. We anticipate this approach may facilitate the creation of next-generation antimicrobials that slow resistance development and could be extended to other viral scaffolds for a broad range of applications.\n\nHighlightsO_LIVastly diverse phagebody libraries containing 107 different members were created.\nC_LIO_LIStructure-informed engineering of viral tail fibers efficiently generated host-range alterations.\nC_LIO_LIPhagebodies prevented the development of bacterial resistance across long timescales in vitro and are functional in vivo.\nC_LI

synthetic biology