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Collections of cells called engrams are thought to represent memories. Although there has been progress in identifying and manipulating single engrams, little is known about how multiple engrams interact to influence memory. In lateral amygdala (LA), neurons with increased excitability during training outcompete their neighbors for allocation to an engram. We examined whether competition based on neuronal excitability also governs the interaction between engrams. Mice received two distinct fear conditioning events separated by different intervals. LA neuron excitability was optogenetically manipulated and revealed a transient competitive process that integrates memories for events occurring closely in time (coallocating overlapping populations of neurons to both engrams) and separates memories for events occurring at distal times (disallocating nonoverlapping populations to each engram). Rashid et al Science 2016- Data for Figs 1-4, S1-S9Excel file with all data presented in manuscript (each sheet corresponds to specific figures as indicated).Rashid et al Science 2016.xlsx

OBJECTIVE. To assess whether HS severity is mirrored at the level of large-scale networks. METHODS. We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 TLE patients with histopathological diagnosis of HS (n=25; TLE-HS) and isolated gliosis (n=19; TLE-G), and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm which simulates functional dynamics from structural network data. RESULTS. Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from grey matter atrophy. CONCLUSIONS. Severe HS is associated with marked remodeling of connectome topology and structurally-governed functional dynamics in TLE, as opposed to isolated gliosis which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales. Data_phen_conn_dryadPhenotypic information and mean connectome feature data for Bernhardt et al. (2019) Temporal lobe epilepsy: hippocampal pathology modulates white matter connectome topology and controllability. Neurology

Premise of the study: Polyploidization is a common and recurring phenomenon in plants and is often thought to be a mechanism of "instant speciation." Whether polyploidization is associated with the formation of new species ("cladogenesis") or simply occurs over time within a lineage ("anagenesis") has never, however, been assessed systematically. Methods: Here, we tested this hypothesis using phylogenetic and karyotypic information from 235 plant genera (mostly angiosperms). We first constructed a large database of combined sequence and chromosome number data sets using an automated procedure. We then applied likelihood models (ClaSSE) that estimate the degree of synchronization between polyploidization and speciation events in maximum likelihood and Bayesian frameworks. Key results: Our maximum likelihood analysis indicated that 35 genera supported a model that includes cladogenetic transitions over a model with only anagenetic transitions, whereas three genera supported a model that incorporates anagenetic transitions over one with only cladogenetic transitions. Furthermore, the Bayesian analysis supported a preponderance of cladogenetic change in four genera but did not support a preponderance of anagenetic change in any genus. Conclusions: Overall, these phylogenetic analyses provide the first broad confirmation that polyploidization is temporally associated with speciation events, suggesting that it is indeed a major speciation mechanism in plants, at least in some genera. PloiDBPhylogenetic trees inferred using MrBayes, ploidy estimates using ChromEvol, and TPL-based genus species diversity estimates for 223 genera.ploidb_dryad.tar.gz

Background: Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings: A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions: Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study. DATA_Terminated Trials in ClinicalTrialsgov Results Database (19 Feb 2013)CSV data file containing data retrieved from the ClinicalTrials.gov registry and results database on February 19, 2013. Additional details are available in the ReadMe file.

Web Supplementary Files Web Supplementary File 1 - FASTA files containing full-length reconstruction input sequences: full_length_reconstruction_input_sequence_fastas.zip Web Supplementary File 2 - FASTA files containing Muscle alignments of the full-length reconstruction input sequences. full_length_reconstruction_input_sequence_alns.zip Web Supplementary File 3 - FASTA file of full-length reconstructed sequences: full_length_reconstructions.fa Web Supplementary File 4 - Table of full-length reconstruction statistics: full_length_reconstruction_stats.csv Web Supplementary File 5 - FASTA files containing ORF reconstruction input sequences: orf_fastas.zip Web Supplementary File 6 - FASTA files containing Macse alignments of the ORF reconstruction input sequences: ORF_reconstruction_input_sequence_alns.zip Web Supplementary File 7 - Table of ORF reconstruction statistics: ORF_reconstructions.fa Web Supplementary File 8 - Table of ORF reconstruction statistics: ORF_reconstruction_stats.csv Web Supplementary File 9 - Table of Composite Sequences: bestfl_selection_fixed_CS_seqs.csv Web Supplementary File 10 - Database of gold standards: L1_goldstandards.csv Data Underlying Figures RepeatMasker scans of hg38 and ancestral genomes: anc_gen_RM_out_files.zip Figure 4 4A Source alignment of 54 composite sequences: 220121_dropped12+L1ME3A_muscle.nt.afa Tree produced using the alignment and FastTree: 220121_dropped12+L1ME3A.tree 4B Source alignment of 67 Dfam L1 subfamily 3’ end models: 200123_dfam_3ends.fa.muscle.aln Tree produced using the alignment: 200123_dfam_3ends.fa.muscle.aln.tree Figure 5 KZFP-TE enrichment p-values (from Barazandeh et al 2018): TE_KZFP_enrichment_pvals.xlsx KZFP-TE top 500 peak overlap (from Barazandeh et al 2018): top500_peak_overlap.xlsx Figure 6 RepeatMasker .out file for the Composite Sequence custom library queried against hg38: CS_RM_hg38.fa.out.gz Figure S2 RepeatMasker scan .out file of hg38 (CG corrected Kimura Divergence values are in last column): hg38+KimDiv_RM.out RepeatMasker scan .out file of the Progressive Cactus eutherian ancestral genome (CG corrected Kimura Divergence values are in last column): Progressive_Cactus_Euth+KimDiv_RM.out RepeatMasker scan .out file of the Ancestors 1.1 eutherian ancestral genome (CG corrected Kimura Divergence values are in last column): Ancestors_Euth+KimDiv_RM.out Figure S5 RepeatMasker scan .out files for Progressive Cactus simian and primate reconstructed ancestral genomes: progCactus_RM_outfiles.zip S5A FASTA files containing Cactus genome-derived reconstructed sequences equivalent to the L1MA2, L1MA4, and L1MD1-3 best full-length sequences: progCactus_reconstruction_bestFL_equivalents.zip S5B FASTA files containing Muscle alignments of Cactus genome-derived full-length reconstruction input sequences: progCactus_reconstruction_input_sequence_alns.zip Figure S6 S6A Results of Conserved Domain scans of Cactus genome-derived full-length reconstructed sequences: CD_search_results_short_nms.txt S6B-D Character posterior probabilities of “best” full-length reconstructed sequences: best_fl_post_probs.zip Figure S7 S7B-C Results of Conserved Domain scans of translated initial full-length reconstructed sequences: initial_recons_all_3frametrans_CD-search.txt Results of Conserved Domain scans of translated reconstructed ORFs: recons_ORF1-2_all_3frametrans_CD-search.csv Figure S15 S15A Source alignment of 67 composite sequences: bestfl_selection_fixed_CS_seqs_muscle.nt.afa Tree produced using the alignment: bestfl_selection_fixed_CS_seqs_muscle.nt.afa.tree S15B-E Source Muscle alignments for phylogenetic trees of reconstructed sequence components: ORF2: ORF2_keep54_muscle.nt.afa 5’ UTR: 5utr_keep54_muscle.nt.afa ORF1: ORF1_keep54_muscle.nt.afa 3’ UTR: 3utr_keep54_muscle.nt.afa Trees produced using above alignments: ORF2: ORF2_keep54_muscle.nt.afa.tree 5’ UTR: 5utr_keep54_muscle.nt.afa.tree ORF1: ORF1_keep54_muscle.nt.afa.tree 3’ UTR: 3utr_keep54_muscle.nt.afa.tree Figure S17 Unfiltered BLAST results of Composite Sequences queried against hg38: CS_hg38_blastn.csv.zip BED file of L1 instances annotated using BLAST pipeline: BLAST_L1_hits.bed

This is the first version of documented best practices in sharing and linking phenotypic and genetic data. It identifies and describes best practices on sharing and linking phenotypic and genetic data in both the healthcare sector and in the research setting. The idea is to, as much as possible, avoid reinventing the wheel, learn from previous/current existing projects to improve performance and avoid mistakes made by others.

Supplemental notes document for the Kanata Declaration.

Supplemental notes document for the Kanata Declaration.

We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene. MC-sample1-HDL-AMAdmixture Mapping results for HDL-cholesterol: Mexico City sample 1MC-sample1-LDL-AMAdmixture Mapping results for LDL-cholesterol: Mexico City sample 1MC-sample1-TCHOL-AMAdmixture Mapping results for Total-cholesterol: Mexico City sample 1MC-sample1-TG-AMAdmixture Mapping results for triglycerides: Mexico City sample 1MC-sample2-HDL-AMAdmixture Mapping results for HDL-cholesterol: Mexico City sample 2MC-sample2-LDL-AMAdmixture Mapping results for LDL-cholesterol: Mexico City sample 2MC-sample2-TCHOL-AMAdmixture Mapping results for Total-cholesterol: Mexico City sample 2MC-sample2-TG-AMAdmixture Mapping results for triglycerides: Mexico City sample 2Mexico-City-AM-signalsAdmixture Mapping signals identified in both Mexico City samples for all the lipid traits.