Community recommendations on cryoEM data archiving and validation

In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 47 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshop’s motivation and history, the topics discussed, and the resulting consensus recommendations. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations.The workshop was supported by funding to PDBe and EMDB by the Wellcome Trust (grant No. 104948/Z/14/Z awarded to GJK, SV and AP) and by the European Molecular Biology Laboratory. Travel was supported by the PDBe, EMDB, RCSB PDB, PDBj, BMRB and EMDR. RCSB PDB is jointly funded by the National Science Foundation (grant No. DBI1832184); the US Department of Energy (grant No. DESC0019749); and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health (grant No. R01GM133198). PDBj is funded by JST-NBDC and BMRB by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) (grant No. R24GM150793). EMDR was funded by the NIGMS of the NIH (grant No. R01GM079429).Peer reviewe

Neural Basis for the Use and Update of Cognitive Maps

University of Minnesota Ph.D. dissertation. August 2020. Major: Neuroscience. Advisors: Benjamin Hayden, Sarah Heilbronner. 1 computer file (PDF); viii, 225 pages.Goal-directed behavior is ubiquitous in our lives, ranging from the pursuit of happiness to simply choosing tea over coffee. The adaptive and successful execution of goal-directed behavior relies on the use of cognitive maps, the mental models of the environments we interact with. Numerous studies have demonstrated the representation of cognitive maps in both hippocampus and the orbitofrontal cortex (OFC). However, how goal information is learned, represented, and used, in coordination with the cognitive maps, to guide behavior, remained largely unknown. We hypothesized that goal simulation interacts with the representation of cognitive map to fulfill this function. This program of research uses reward-based decision making and 3D virtual reality foraging tasks in rhesus monkeys, with electrophysiology recording and anatomical approaches, to address this question and test our goal simulation hypothesis. We found that OFC evaluates and infers from experience to represent and update the cognitive map. Posteromedial regions, retrosplenial cortex (RSC) and posterior cingulate cortex (PCC) uses learned goal information to guide behavior. Crucially, we identified an orbito-posteromedial axis that is anatomically directly connected and translates abstract goal information into concrete action plans for guiding behavior

Curiosity from the Perspective of Systems Neuroscience

Curiosity refers to a demand for information that has no instrumental benefit. Because of its critical role in development and in the regulation of learning, curiosity has long fascinated psychologists. However, it has been difficult to study curiosity from the perspective of the single neuron, the circuit, and systems neuroscience. Recent advances, however, have made doing so more feasible. These include theoretical advances in defining curiosity in animal models, the development of tasks that manipulate curiosity, and the preliminary identification of circuits responsible for curiosity-motivated learning. Taken together, resulting scholarship demonstrates the key roles of executive control, reward, and learning circuits in driving curiosity; and has helped us to understand how curiosity relates to information-seeking more broadly. This work has implications for mechanisms of reward-based decisions in general. Here we summarize these results and highlight important remaining questions for the future of curiosity studies

Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy

Background: During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure. Methods: We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish and Drosophila models were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further. Results: Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identified RTTN, the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient's condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes. Conclusions: This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role for RTTN in perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease.</p

Community recommendations on cryoEM data archiving and validation.

In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 47 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshops motivation and history, the topics discussed, and the resulting consensus recommendations. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations

Appreciation to referees, 2023

Saif Benjaafar, Editor-in-Chief of Service Science, thanks the referees who have generously provided expert counsel and guidance on a voluntary basis to the journal. Without them, the journal would not be able to function. The following list acknowledges those who acted as referees for papers considered during this past calendar year

Community recommendations on cryoEM data archiving and validation.

In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 47 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshop's motivation and history, the topics discussed, and the resulting consensus recommendations. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations