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Additional file 1. Appendix

Additional file 3: Table S3. GR methylation in U and C regions for patients by outcome.

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Additional file 12: Table S1. Total number of ones, zeros and nulls in the sparse matrix for the 163 TFs used in this study.

Additional file 2: Table S2. Summary of CHG-based DMGs.

Introduction: The threat bacterial pathogens pose to human health is increasing with the number and distribution of antibiotic-resistant bacteria, while the rate of discovery of new antimicrobials dwindles. Proteomics is playing key roles in understanding the molecular mechanisms of bacterial pathogenesis, and in identifying disease outcome determinants. The physical associations identified by proteomics can provide the means to develop pathogen-specific treatment methods that reduce the spread of antibiotic resistance and alleviate the negative effects of broad-spectrum antibiotics on beneficial bacteria. Areas covered: This review discusses recent trends in proteomics and introduces new and developing approaches that can be applied to the study of protein-protein interactions (PPIs) underlying bacterial pathogenesis. The approaches examined encompass options for mapping proteomes as well as stable and transient interactions in vivo and in vitro. We also explored the coverage of bacterial and human-bacterial PPIs, knowledge gaps in this area, and how they can be filled. Expert commentary: Identifying potential antimicrobial candidates is confounded by the complex molecular biology of bacterial pathogenesis and the lack of knowledge about PPIs underlying this process. Proteomics approaches can offer new perspectives for mechanistic insights and identify essential targets for guiding the discovery of next generation antimicrobials.

Detailed variant information for all verified variants, including ACMG classification â Table showing details for variant classification such as pathogenicity prediction algorithms results and details of ACMG criteria application. (XLSX 18 kb)

Targets for goal-directed action can be encoded in allocentric coordinates (relative to another visual landmark), but it is not known how these are converted into egocentric commands for action. Here, we investigated this using a slow event-related fMRI paradigm, based on our previous behavioral finding that the Allocentric to Egocentric (Allo-Ego) conversion for reach is done at the first possible opportunity. Participants were asked to remember (and eventually reach toward) the location of a briefly presented target relative to another visual landmark. After a 1st memory delay, participants were forewarned by a verbal instruction if the landmark would reappear at the same location, (potentially allowing them to plan a reach following the auditory cue before the 2nd delay), or at a different location where they had to wait for the final landmark to be presented before response, and then reach toward the remembered target location. As predicted, participants showed landmark-centered directional selectivity in occipital-temporal cortex during the first memory delay, only developed egocentric directional selectivity in occipital-parietal cortex during the second delay for the “Same cue” task, and during response for the “Different cue” task. We then compared cortical activation between these two tasks at the times when the Allo-Ego conversion occurred, and found common activation in right precuneus, right pre-supplementary area and bilateral dorsal premotor cortex. These results confirm that the brain converts allocentric codes to egocentric plans at the first possible opportunity, and identify the four most likely candidate sites specific to the Allo-Ego transformation for reaches.