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Dill, K. A.

Publications and source records attributed to Dill, K. A..

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Outcomes of the 2019 EMDataResource model challenge: validation of cryo-EM models at near-atomic resolution

This paper describes outcomes of the 2019 Cryo-EM Map-based Model Metrics Challenge sponsored by EMDataResource (www.emdataresource.org). The goals of this challenge were (1) to assess the quality of models that can be produced using current modeling software, (2) to check the reproducibility of modeling results from different software developers and users, and (3) compare the performance of current metrics used for evaluation of models. The focus was on near-atomic resolution maps with an innovative twist: three of four target maps formed a resolution series (1.8 to 3.1 [A]) from the same specimen and imaging experiment. Tools developed in previous challenges were expanded for managing, visualizing and analyzing the 63 submitted coordinate models, and several novel metrics were introduced. The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual laboratory experiments and holdings of structure data archives such as the Protein Data Bank. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived from these benchmark maps by 13 participating teams, representing both widely used and novel modeling approaches. We also evaluate the pros and cons of the commonly used metrics to assess model quality and recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed density in the cryo-EM map.

biochemistry

Younger, but not older, brains are poised at a critical point of functional activity

Brain aging is associated with hypometabolism and associated global changes in functional connectivity. Using fMRI, we show that network synchrony, a collective property of brain activity, decreases with age. Applying quantitative methods from statistical physics, we provide a generative (Ising) model for these changes as a function of the average communication strength between brain regions. In particular, we find healthy brains to be poised at a critical point of this communication strength, enabling a balance between segregated (to functional domains) and integrated (between domains) patterns of synchrony. However, one characteristic of criticality is a high sensitivity to small changes. Thus, minute weakening of pairwise communication between regions, as seen in the aging brain, gives rise to qualitatively abrupt changes in synchrony. Finally, by experimentally modulating metabolic activity in younger adults, we show how metabolism alone-independent of other changes associated with aging-can provide a mechanism for global changes in synchrony.

neuroscience