Metrics details An Author Correction to this article was published on 16 October 2023 This article has been updated The amygdala processes positive and negative valence and contributes to addiction but the cell-type-specific gene regulatory programs involved are unknown We generated an atlas of single-nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with high and low cocaine addiction-like behaviors following prolonged abstinence Differentially expressed genes between the high and low groups were enriched for energy metabolism across cell types Rats with high addiction index (AI) showed increased relapse-like behaviors and GABAergic transmission in the amygdala Both phenotypes were reversed by pharmacological inhibition of the glyoxalase 1 enzyme which metabolizes methylglyoxal—a GABAA receptor agonist produced by glycolysis Differences in chromatin accessibility between high and low AI rats implicated pioneer transcription factors in the basic helix-loop-helix We observed opposite regulation of chromatin accessibility across many cell types excitatory neurons had greater accessibility in high AI rats and inhibitory neurons had greater accessibility in low AI rats the role of distinct neuronal and non-neuronal cell subpopulations in addiction remains unclear these previous studies used inbred rodent strains which limited examination of genetically mediated differences in susceptibility to addiction-like behaviors these studies focused on acute drug treatments and therefore did not explore molecular changes that accompany long-lasting addictive-like behaviors Individual differences in total number of cocaine rewards in self-administration (SA) PR and shock-paired (Shock) sessions for each rat Mean number of cocaine rewards across each ShA and LgA IVSA session in high (n = 21) and low (n = 25) AI rats Breakpoint analysis of high (n = 21) and low (n = 25) AI rats under ShA versus LgA (unpaired two-sided Studentʼs t-test with Bonferroni adjusted P = 0.0001; ShA versus LgA for high AI rats Mean number of cocaine rewards when paired with electric footshock in high (n = 21) and low AI (n = 25) rats (P = 0.0003; unpaired two-sided Studentʼs t-test These results show that our model of extended access to cocaine IVSA in outbred rats captures several relevant aspects of cocaine use disorder UMAP plot of snRNA-seq data from rat amygdala Cells are colored by cluster assignments performed with KNN analysis We assigned cell-type labels to clusters based on the expression of known marker genes UMAP plot of snATAC-seq data from 12 rat amygdala samples snATAC-seq data were integrated with snRNA-seq data and cluster labels were transferred to snATAC-seq cells Feature plot showing expression of marker genes used to label main subsets of cells: Gja1 (astrocytes) Gad1/Gad2 (inhibitory neurons) and Cldn5 (endothelial cells) Feature plot showing imputed gene expression of cell-type-specific marker genes in snATAC-seq dataset Expression of marker genes in cell clusters corresponding to highly specific subsets of inhibitory neurons The shading and diameter of each circle indicate the estimated mean expression and the percentage of cells in the cluster in which the marker gene was detected The number of nuclei assigned to each cell-type cluster for the snATAC-seq and snRNA-seq datasets The snRNA-seq and snATAC-seq datasets we generated are the first single-cell atlas of molecularly defined cell types in the rat amygdala under normal conditions and during cocaine addiction-like behaviors Volcano plot summarizing differential gene expression between high and low AI rats based on a two-sided negative binomial test and the five most significant (FDR < 10%) up- and downregulated genes in each cell type are indicated with labels we normalized the logFC values reported by Seurat to convert to z-scores and plotted the cell-type-specific z-scores on the x axis (z > 0 indicates higher expression in high AI rats; z < 0 indicates higher expression in low AI rats) The –log10FDR-corrected P values (Q values) are plotted on the y axis Volcano plot summarizing differential gene expression based on a two-sided negative binomial test between high and low AI rats for non-neuronal (glial) cell-type clusters Violin and embedded boxplots showing distribution of log2FC from the negative binomial (negbinom) test performed in 1,000 bootstrap iterations Fractions indicate the number of bootstrap iterations in which the log2FC estimate was significantly different from 0 Boxplot hinges are the 25th and 75th percentiles; whiskers extend to the minimum and maximum; center line is the median and dotted line is the mean Bootstrap distributions were obtained for cell types in which the following genes had significant differential expression (FDR < 10%): Kcnq3 (c) KEGG pathways that are enriched for DEGs by cell type Dot size indicates –log10(Q) while color indicates normalized enrichment score (NES) Only pathways/cell types where Q < 0.1 are visualized These observations indicate that genetic differences in high versus low AI rats contribute to some of the observed differences in expression Cocaine exposure probably also plays a role; however quantifying the relative contributions of cocaine and genetics is challenging due to limitations in the genetic predictions of gene expression These observations suggest that addiction-like behaviors are associated with alterations in the metabolic state of amygdalar cell populations which can directly impact neural network activity in the amygdala Schematic showing animal model used for electrophysiology recording in CeA slices from HS rats subjected to 4 weeks of abstinence from cocaine IVSA Electrophysiological recordings were taken before and after pBBG treatment from tissue slices of five naive Baseline sIPSC frequency before pBBG injection A significant difference between the means of the naive versus high AI rats was observed (adjusted P = 0.004 Tukey’s honestly significant difference test) We observed significantly reduced frequency in the CeA slices from high and low AI rats but not in naive rats when we compare baseline versus pBBG in each group (Phigh = 7.6 × 10–5; Plow = 3.4 × 10–3 Change in sIPSC frequency following pBBG treatment in naive (d) Schematic of animal model used to test cue-induced cocaine-seeking behavior Rats with low and high AI were injected with vehicle or pBBG following a period of prolonged abstinence and re-exposed to SA chambers in the absence of cocaine cocaine-seeking behavior in high AI rats (n = 12) was reduced by pBBG treatment (unpaired Student’s t-test with Bonferroni adjusted P = 0.024 Rats were subjected to the same operant conditions of cocaine IVSA but without drug availability and reinstatement was triggered by re-exposure to the cocaine infusion-associated light cue A significant interaction between AI and pBBG treatment (two-way repeated-measures ANOVA P < 0.05) indicated that pBBG reduced cue-induced reinstatement in high AI rats (P value < 0.05 post hoc comparisons with Bonferroni correction) These results demonstrate that modulating GABAA transmission via the pharmacological inhibition of GLO1 decreases relapse-like behaviors in animals with high cocaine AI indicating that differences in addiction-like behaviors between rats are associated with modest regulatory changes at a large number of sites These biases probably reflect altered activity of transcription factors (TFs) controlling large transcriptional programs These findings confirm that the differences in chromatin accessibility and gene expression are concordant This enrichment may indicate that changes in chromatin associated with addiction-like behaviors are more concentrated at promoters or that we have greater statistical power to detect changes at promoters due to larger effect sizes or greater chromatin accessibility suggesting that a different mechanism might affect their activity suggesting that differences in their expression level affect their regulatory activity These results implicate many motif clusters associated with addiction-like behaviors across thousands of regulatory regions and in a cell-type-specific manner with the most significant enrichments in neurons These results indicate that the regulatory architecture of HS rats is relevant for human addiction-related traits The snATAC-seq dataset is the first map of cell-type-specific regulatory elements in the amygdala enabling the identification of TF motifs that may drive addiction-related processes These explanations are not mutually exclusive and it is probable that some differences are caused by eQTLs while others are caused by differences in the activity of upstream regulators (which themselves may be affected by genetics or other factors) An alternative scenario is that the magnitude of effects is not sufficient to cause detectable changes in amplitude these results offer a new pharmacological target for improving therapeutic approaches for cocaine addiction Future experiments targeting specific subregions or cell types of the amygdala will be necessary to further characterize the effects of GLO1 inhibition on cocaine addiction-related phenotypes Future experiments that directly manipulate the expression of specific metabolic enzymes or pioneer TFs in a cell-type-specific manner will be necessary to fully elucidate their role in addiction the amygdalar cellular atlas produced by this study is a valuable resource for understanding the role of cell-type-specific gene regulatory programs in the development of cocaine addiction-related behaviors Our results emphasize the importance of cellular energetics and GABAA-mediated signaling in the enduring effects of cocaine use and identify GLO1 as a potential new target for the treatment of cocaine addiction Cocaine HCl (National Institute on Drug Abuse) was dissolved in 0.9% saline and administered intravenously at a dose of 0.5 mg kg–1 per infusion pBBG was synthesized in the laboratory of D Siegel (Skaggs School of Pharmacy and Pharmaceutical Sciences pBBG was dissolved in a vehicle of 8% dimethylsulfoxide 18% Tween-80 and 74% distilled water and administered intraperitoneally 30 min before the test session Behavioral data was collected with the MedPCIv v.5 software Brain tissues were extracted and snap-frozen (at –30 °C) Cryosections of 500 μm (Bregma –1.80 to 3.30 mm) were used to dissect the amygdala BLA and medial amygdala from both hemispheres Punches from three sections were combined for each rat six ACI/EurMcw rats were used for dissection of the CeA and BLA snRNA-seq libraries from whole amygdala tissues were generated by the Center for Epigenomics frozen tissue was homogenized via glass dounce Nuclei were resuspended in 500 µl of nuclei permeabilization buffer (0.1% Triton-X-100 (Sigma-Aldrich 1 mM DTT and 1 U µl–1 RNase inhibitor (Promega 2% bovine serum albumin (BSA; Sigma-Aldrich Samples were incubated on a rotator for 5 min at 4 °C and then centrifuged at 500g for 5 min (4 °C) Pellets were resuspended in 400 µl of sort buffer (1 mM EDTA SRE0036) in PBS) and stained with DRAQ7 (1:100; Cell Signaling Up to 75,000 nuclei were sorted using a SH800 sorter (Sony Cell Sorter Software v.2.1.2-5) into 50 µl of collection buffer consisting of 1 U µl–1 RNase inhibitor in 5% BSA Sorted nuclei were centrifuged at 1,000g for 15 min at 4 °C and then resuspended in 35 µl of reaction buffer (0.2 U µl–1 RNase inhibitor (Promega 12,000 nuclei were loaded onto a Chromium Controller (10x Genomics) Libraries were generated using the Chromium Single-Cell 3′ Library Construction Kit v.3 (10x Genomics 1000075) with the Chromium Single-Cell B Chip Kit (10x Genomics 1000153) and the Chromium i7 Multiplex Kit for sample indexing (10x Genomics 120262) according to manufacturer specifications Frozen amygdala tissue was homogenized using a 2 ml glass dounce with 1 ml cold homogenization buffer (0.26 M sucrose The cell suspension was filtered using a 70 μm Flowmi strainer (Millipore Sigma BAH136800070) and centrifuged at 350g for 5 min at 4 °C Nuclei were isolated by iodixanol (Millipore Sigma The nuclei iodixanol solution (25%) was layered on top of 40% and 30% iodixanol solutions Samples were centrifuged in a swinging bucket centrifuge at 3,000g for 20 min at 4 °C Nuclei were isolated from the 30–40% interface Nuclei were washed in ATAC-RSB-Tween buffer (0.01 M Tris-HCl pH 7.5 0.1% Tween-20) and then resuspended in nuclei resuspension buffer (10x Genomics 12,000 nuclei were loaded on the 10x Genomics Chromium Controller for GEM (gel bead in emulsion) generation Libraries were generated using the Chromium Next GEM Single Cell ATAC v.1.1 (10x Genomics PN-1000175) with the Chromium Next GEM Chip H Single Cell Kit (10x Genomics 1000162) and the Chromium i7 Multiplex Kit for sample indexing (10x Genomics 1000212) according to manufacturer specifications frozen brain tissues were obtained from the ACI/EurMcw rat strain—one of the HS rat founder strains Nuclei were isolated as described above for snATAC-seq libraries 03335402001) were added to all buffers (1 U μl–1) 12,000 nuclei were loaded on the 10x Genomics Chromium Controller for GEM generation Libraries were generated using the Chromium Next GEM Single Cell Multiome Reagent Kit A (catalog no 1000282) following Chromium Next GEM Single Cell Multiome ATAC + Gene Expression Reagent Kits User Guide (10x Genomics) Next-generation sequencing libraries were constructed following the User Guide Final libraries were sequenced using the NovaSeq6000 (Illumina) Data were analyzed using Prism v.9.0 software (GraphPad) SA data were analyzed using repeated-measures ANOVA or mixed effect model followed by Bonferroni post hoc tests when appropriate data were analyzed using the unpaired t-test Values of P < 0.05 were considered statistically significant Data distributions were assumed to be normal Experimenters were blinded to group allocation during behavioral data collection before brain collection CeA slices were prepared after 4 weeks of abstinence from cocaine IVSA following the same behavioral protocol described above or age-matched naive rats that received sham IV surgery These rats were distinct from those used for snRNA-seq and snATAC-seq and included five high AI Slices from each group were also used to record sIPSCs after pBBG treatment Brain tissues were placed in oxygenated (95% O2 5% CO2) ice-cold cutting solution (206 mM sucrose Transverse slices (300 μm thick) were cut on a Vibratome (Leica VT1200S; Leica Microsystems) and transferred to oxygenated artificial cerebrospinal fluid (130 mM NaCl 26 mM NaHCO3 and 10 mM glucose) for 30 min at 35 °C and then at room temperature for the rest of the experiment conducted in a recording chamber mounted on the stage of an upright microscope (Olympus The slices were perfused continuously with oxygenated artificial cerebrospinal fluid at a rate of 3 ml min–1 Whole-cell recordings were performed using a Multiclamp 700B amplifier (10 kHz sampling rate 10 kHz low-pass filter) and Digidata 1440A and pClamp 10 software (Molecular Devices) Patch pipettes (4–6 MΩ) were pulled from borosilicate glass (Warner Instruments) and filled with 70 mM KMeSO4 Pharmacologically isolated sIPSCs were recorded in the presence of the glutamate receptor blockers 189) and the GABA-B receptor antagonist CGP55845 (Tocris Experiments with a series resistance of >15 MΩ or >20% change in series resistance were excluded from the final dataset pBBG (2.5 μM) was acutely applied in the bath amplitude and kinetics of sIPSCs were analyzed using semiautomated threshold-based minidetection software (Easy Electrophysiology) and confirmed visually Data were analyzed using Prism v.9.0 software (GraphPad) with one-way ANOVA followed by post hoc Tukey honestly significant difference test or with paired t-tests Data are expressed as mean ± s.e.m unless otherwise specified To compare CeA and BLA subregion samples with the whole amygdala we subsampled whole amygdala samples from the naive rats and performed the same integration technique The integrated subregion data was visualized using UMAP implemented with the ‘FindMarkers()’ function in Seurat Cell type identities were assigned based on expression of known marker genes We used ClusterProfiler118 to perform GSEA of KEGG pathways A ranked list of the avg_logFC values for all genes evaluated with our negative binomial test was given as input to GSEA Multiple testing correction for GSEA results was performed using Benjamini–Hochberg adjustment with statistical significance assessed at FDR < 10% Conditionally independent cis-eQTLs (FDR < 5%) were downloaded from the RatGTEx portal (https://ratgtex.org/download/) We examined cis-eQTLs in the following brain tissues: BLA We assessed enrichment of significant DEGs (FDR < 10%) that also had eQTLs in the rat brain with a Chi-squared test Spearman correlation confidence intervals (CIs) were calculated using \(\tan h \left(\tan {h}^{-1}(\,\rho )\pm \frac{1.96}{\sqrt{N-3}}\right)\) We then performed nonlinear dimensionality reduction and clustering with UMAP and KNN Raw counts were used for downstream differential accessibility analyses This process returns a classification score for each cell for each cell type defined in the scRNA-seq data Each cell was assigned the cell-type identity with the highest score By identifying matched cells in the snRNA-seq dataset we were able to impute RNA expression values for each cell in our snATAC-seq dataset library batch date and rat sample identification number as covariates Multiple testing correction was performed using the Benjamini–Hochberg method and FDR < 10% was used to determine statistical significance Permutation tests were performed in the same manner as the differential gene expression analyses using the baseline model and standard regression weights from the LDSC Partitioned Heritability tutorial we ran a cell-type-specific partitioned heritability analysis we generated a 2 × 2 contingency table for the FET where the cells contained the following counts: differential peaks with a TSS/promoter annotation; differential peaks without a TSS/promoter annotation; nondifferential peaks (FDR > 10%) with a TSS/promoter annotation and nondifferential peaks (FDR > 10%) without a TSS/promoter annotation we obtained gene coordinates from the TxDb.Rnorvegicus.UCSC.rn6.refGene annotation package and defined promoter regions as –1,500 bases upstream to +500 bases downstream of the TSS We then generated a 2 × 2 contingency table for the FET that contained the number of DEGs with DA promoters non-DEGs with DA promoters and non-DEGs with non-DA promoters We measured cell-type-specific motif activities using chromVAR to test for per motif deviations in accessibility between nuclei from high versus low AI rats Motif data was pulled from the JASPAR2020 database and integrated with snATAC-seq data using the ‘AddMotifs()’ function in Signac After adding motifs to our snATAC-seq dataset we ran the ‘RunChromVAR()’ wrapper in Signac Differential analysis of chromVAR deviation scores was performed using the Wilcoxon rank-sum test between high versus low AI rats in each cell type Differential testing was performed using Seurat’s ‘FindMarkers()’ function with the mean function set as ‘rowMeans()’ to calculate average difference in deviation scores between groups Multiple testing correction was performed using Benjamini–Hochberg adjustment and FDR < 10% was used to determine statistical significance Motif clusters were defined using the cluster numbers from JASPAR’s matrix clustering-results and the names of the clusters were annotated manually we retrieved the top 50 most significant motifs (FDR < 10%) per cell type Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article All code used to perform analyses in this paper can be found at https://github.com/mcvickerlab/sn_cocaine_rats A Correction to this paper has been published: https://doi.org/10.1038/s41593-023-01489-z From circuits to behaviour in the amygdala The central amygdala and alcohol: role of γ-aminobutyric acid Buffalari, D. M. & See, R. E. in Behavioral Neuroscience of Drug Addiction (eds. Self, D. W. & Staley Gottschalk, J. K.) (Springer, 2010); https://doi.org/10.1007/7854_2009_18 Koob, G. F. in Anhedonia: Preclinical, Translational, and Clinical Integration (ed. Pizzagalli, D. A.) (Springer, 2022); https://doi.org/10.1007/7854_2021_288 Neurobiology of the incubation of drug craving The neural basis of addiction: a pathology of motivation and choice Neural activity related to drug craving in cocaine addiction Novel perspectives on the development of the amygdala in rodents Amygdala inhibitory circuits and the control of fear memory Encoding of conditioned fear in central amygdala inhibitory circuits A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex Molecular logic of cellular diversification in the mouse cerebral cortex Single-cell epigenomics reveals mechanisms of human cortical development Epigenomic diversity of cortical projection neurons in the mouse brain An atlas of gene regulatory elements in adult mouse cerebrum A human cell atlas of fetal chromatin accessibility A single-cell atlas of chromatin accessibility in the human genome Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain Decoding molecular and cellular heterogeneity of mouse nucleus accumbens Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum An atlas of transcriptionally defined cell populations in the rat ventral tegmental area Single-cell RNA-Seq uncovers a robust transcriptional response to morphine by Glia A dopamine-induced gene expression signature regulates neuronal function and cocaine response two repositories from genetically diverse and behaviorally characterized rats for the study of addiction.eNeuro 8 Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking Robust escalation of nicotine intake with extended access to nicotine self-administration and intermittent periods of abstinence Using heterogeneous stocks for fine-mapping genetically complex traits Development of the National Institutes of Health genetically heterogeneous rat stock SNP and haplotype mapping for genetic analysis in the rat Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.Nat Leptin protects against the development and expression of cocaine addiction-like behavior in heterogeneous stock rats Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake and breaking-points are highly correlated measures of the same construct Individual differences in addiction-like behaviors and choice between cocaine versus food in heterogeneous stock rats Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments Integrating single-cell transcriptomic data across different conditions Molecular architecture of the mouse nervous system Molecular diversity and specializations among the cells of the adult mouse brain Shared and distinct transcriptomic cell types across neocortical areas BRAIN Initiative Cell Census Network (BICCN A multimodal cell census and atlas of the mammalian primary motor cortex Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala Neuronal diversity of the amygdala and the bed nucleus of the stria terminalis Tackling the widespread and critical impact of batch effects in high-throughput data.Nat A benchmark of batch-effect correction methods for single-cell RNA sequencing data The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats.Nucleic Acids Res Dopamine drives neuronal excitability via KCNQ channel phosphorylation for reward behavior The neuronal KCNQ channel opener retigabine inhibits locomotor activity and reduces forebrain excitatory responses to the psychostimulants cocaine FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.Neuropsychopharmacology 48 Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype Morphine and cocaine increase serum- and glucocorticoid-inducible kinase 1 activity in the ventral tegmental area Quantifying the regulatory effect size of cis-acting genetic variation using allelic fold change Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis An energy budget for signaling in the grey matter of the brain Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal A metal-binding pharmacophore library yields the discovery of a glyoxalase 1 inhibitor Inhibition of glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data Pioneer factor neuroD1 rearranges transcriptional and epigenetic profiles to execute microglia-neuron conversion Putting chromatin in its place: the pioneer factor NeuroD1 modulates chromatin state to drive cell fate decisions Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype but not the protective depression phenotype of environmental enrichment Transcriptional mechanisms of drug addiction Cocaine self-administration alters transcriptome-wide responses in the brain’s reward circuitry ΔFosB: a sustained molecular switch for addiction Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments Induction of chronic Fos-related antigens in rat brain by chronic morphine administration Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens Network-level changes in expression of inducible Fos–Jun proteins in the striatum during chronic cocaine treatment and withdrawal LD score regression distinguishes confounding from polygenicity in genome-wide association studies Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use Leveraging genome-wide data to investigate differences between opioid use vs opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium Compulsive-like responding for opioid analgesics in rats with extended access Responses to novelty and vulnerability to cocaine addiction: contribution of a multi-symptomatic animal model Discovery and implications of polygenicity of common diseases Pioneer transcription factors initiating gene network changes Genome wide association study in 3,173 outbred rats identifies multiple loci for body weight Kappa opioid receptor-mediated dysregulation of GABAergic transmission in the central amygdala in cocaine addiction GABAA receptor subtype involvement in addictive behaviour Inhibiting subthalamic nucleus decreases cocaine demand and relapse: therapeutic potential The role of dopaminergic signaling in the medial prefrontal cortex for the expression of cocaine-induced conditioned place preference in rats Early-life adversity selectively impairs α2-GABAA receptor expression in the mouse nucleus accumbens and influences the behavioral effects of cocaine Role of the GABAa and GABAb receptors of the central nucleus of the amygdala in compulsive cocaine-seeking behavior in male rats Opposite effects of basolateral amygdala inactivation on context-induced relapse to cocaine seeking after extinction versus punishment Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats Prelimbic cortical projections to rostromedial tegmental nucleus play a suppressive role in cue-induced reinstatement of cocaine seeking Baclofen acts in the central amygdala to reduce synaptic transmission and impair context fear conditioning Presynaptic inhibition of GABA release in the BNST by kappa opioid receptor signaling Neuronal overexpression of Glo1 or amygdalar microinjection of methylglyoxal is sufficient to regulate anxiety-like behavior in mice Tightly coupled brain activity and cerebral ATP metabolic rate Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: a new perspective Partitioning heritability by functional annotation using genome-wide association summary statistics Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats Meningeal lymphatics modulate microglial activation and immunotherapy in Alzheimer’s disease Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced transcriptional and behavioral plasticity in male rats Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving Neuroadaptations in the dorsal hippocampus underlie cocaine seeking during prolonged abstinence Synaptic microtubule-associated protein EB3 and SRC phosphorylation mediate structural and behavioral adaptations during withdrawal from cocaine self-administration Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes Glucocorticoid receptor-regulated enhancers play a central role in the gene regulatory networks underlying drug addiction Evidence for addiction-like behavior in the rat Pattern of intake and drug craving predict the development of cocaine addiction-like behavior in rats Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion Massively parallel digital transcriptional profiling of single cells JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles Comprehensive integration of single-cell data Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression.Genome Biol Richards, L. M. et al. A comparison of data integration methods for single-cell RNA sequencing of cancer samples. Preprint at bioRxiv https://doi.org/10.1101/2021.08.04.453579 (2021) MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data clusterProfiler 4.0: a universal enrichment tool for interpreting omics data Single-cell chromatin state analysis with Signac BEDTools: a flexible suite of utilities for comparing genomic features BSgenome.Rnorvegicus.UCSC.rn6: full genome sequences for Rattus norvegicus (UCSC version rn6) Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing sensitive and accurate integration of single-cell data with Harmony Negative binomial mixed models for analyzing longitudinal CD4 count data PLINK: a tool set for whole-genome association and population-based linkage analyses Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities Download references Preissl from the UCSD School of Medicine Center for Epigenomics for technical assistance with the snRNA-seq library preparation Hightower for assistance with figure preparation Schweitzer for technical assistance with sample collection and equipment maintenance Solberg Woods for HS rats breeding colony management This work was supported by the National Institutes of Health (NIH) (grant no was supported by the Brain and Behavior Research Foundation 2020 Young Investigator Award was supported by the TRDRP (T31KT1859 UC) grant This publication includes data generated at the UCSD IGM Genomics Center utilizing an Illumina NovaSeq6000 that was purchased with funding from the NIH (grant no Bioinformatics and Systems Biology Program Department of Integrative Structural and Computational Biology University of Washington School of Medicine designed the overall bioinformatics analysis flow conducted bioinformatic analysis and data interpretation with inputs from F.T. designed the behavioral protocol for cocaine IVSA performed the electrophysiological experiments performed the snRNA-seq experiments for the CeA and BLA coordinated and executed the gene expression predictions for naive HS rats using eQTL data provided genotype data for exploratory analysis wrote the manuscript with contributions from all authors holds a patent related to the use of GLO1 inhibitors (US20160038559 All other authors declare no competing interests Elizabeth Heller and Kristen Maynard for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations List of snRNA-seq rat samples included in analysis batch information and Cell Ranger summary metrics List of snATAC-seq rat samples included in analysis Per nucleus metrics for all nuclei in snRNA-seq dataset after filtering This table contains selected columns from the metadata table for the Seurat object containing the integrated snRNA-seq data Per nucleus metrics for all nuclei in snATAC-seq dataset after filtering This table contains selected columns from the metadata table for the Signac object containing the integrated snATAC-seq data All cell-type-specific differential gene expression analysis results Results of permutation test for differential gene expression analysis using negative binomial test All DEGs (FDR < 10%) that also have eQTLs in the rat brain with a list of variant IDs for corresponding eQTLs All cell-type-specific differential peak accessibility analysis results Permutation test for differential peak accessibility analysis results using negative binomial test Peak annotations for all OCRs in integrated snATAC-seq dataset Download citation DOI: https://doi.org/10.1038/s41593-023-01452-y Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Findings could help address an unmet medical need and shed light on the molecular underpinnings of addiction Researchers at University of California San Diego School of Medicine and the Salk Institute for Biological Studies have created a unique, cell-by-cell atlas of the amygdala, a small structure deep within the brain that plays a crucial role in controlling emotional responses to drugs. The findings, published October 5, 2023 in Nature Neuroscience helped the researchers identify a potential new treatment for cocaine addiction a disease that is poorly understood at the molecular level and has virtually no approved pharmacological treatments “There are some drugs that can help treat other addictions, such as those to opioids or nicotine, but there are currently no safe and effective drugs approved for cocaine addictions,” said co-senior author Francesca Telese, PhD an associate professor in the Department of Psychiatry at UC San Diego School of Medicine “These findings help address that problem and could also point to universal molecular mechanisms of addiction that we haven’t understood until now.” Cocaine is a widely used illicit drug and addiction to cocaine is a major public health concern, associated with a rising number of overdose deaths and a high rate of relapse. Despite the threat cocaine addiction poses, not every person who uses cocaine develops an addiction. According to the National Survey on Drug Use and Health an estimated 4.8 million people used cocaine in 2021 while only 1.4 million people had a cocaine use disorder “Some people use cocaine recreationally and never develop an addiction while others are extremely susceptible to addiction after very little exposure to the drug or may relapse even after years of abstinence,” said Telese “Our long-term goal is to understand why there are these inter-individual differences in drug addiction behavior.” both professors in the Department of Psychiatry at UC San Diego School of Medicine “The Cocaine Biobank is an exceptional resource and was invaluable for this study because it allowed us to study a cohort of rats with a large amount of genetic variety which mimics the diversity we see in human populations,” said Telese using a model of cocaine addiction where rats administered the drug to themselves let us look at the connection between our molecular discoveries and actual addiction behaviors.” The team used single-cell sequencing to determine what genes were expressed in individual cells from the rats’ amygdala a part of the brain that is central to processing emotions and is highly active in people with addictions "Being able to look at individual amygdala cells from rats with different vulnerabilities to addiction was an asset for our study because we wanted to understand how specific cell populations of the amygdala contribute to addiction development,” Telese added To make sense of the large amount of data generated through their sequencing experiments, Telese collaborated closely with bioinformatics expert and co-senior author Graham McVicker, PhD an associate professor at the Salk Institute of Biological Studies and an assistant adjunct professor in the Department of Cellular & Molecular Medicine at UC San Diego School of Medicine a UC San Diego graduate student working with McVicker developed the bioinformatics workflow needed to assemble their sequencing data into a molecular atlas of the rat amygdala The results revealed never-before-seen connections between addiction behaviors and genes involved in energy metabolism “This tells us that energy metabolism may be playing a key role in the activity of neurons in the amygdala and that this effect could be contributing to addiction-like behaviors,” said Telese “This is a brand-new way of thinking about the molecular biology of cocaine addiction.” both assistant adjunct professors in the Department of Psychiatry at UC San Diego School of Medicine “The fact that we were able to link our findings at the cellular level to behaviors exhibited in the rats and were even able to modify these behaviors with a drug puts us one step closer to understanding the extremely complex mechanisms in the brain driving addiction and relapse,” added Telese The researchers are now working on larger sample-size studies that can help determine how much of the effects they observed were based on preexisting genetics in the rats and how much were based on responses to extensive cocaine usage “This research suggests that preexisting genetics may play a much bigger role in addiction than we’ve previously understood,” said Telese “Unraveling these genetics will be key to improving personalized medicine for addictions If we don’t understand the risk of relapse in individual people we can’t fully understand the disease.” Co-authors of the study include: Giordano de Guglielmo Hai-Ri Li and Lieselot LG Carrette at UC San Diego Ho at the Salk Institute for Biological Studies and Pejman Mohammadi at Scripps Research and University of Washington by the National Institutes of Health (grants U01DA050239 the Brain and Behavior Research Foundation and the Tobacco Related Disease Research Program (grant T31KT1859 UC) Palmer holds a patent related to the use of GLO1 inhibitors (US20160038559 This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Ryan Telese of Glen Cove is the latest Long Islander (the seventh in the past six years) to win a four-year full ride to college through the Chick Evans Scholarship a national program that rewards caddies who show leadership Just spending a summer in the caddie yard is an education in itself Ryan Telese of Glen Cove learned that right away enjoying every minute of being around people of varied ages and walks of life What he never expected was that carrying bags at The Creek in Locust Valley would pay for his entire four years at college I didn't ever think I'd be awarded something like this It's such a longshot," he said on the phone from Penn State where he is two weeks into his freshman year it is not as much of a longshot as it used to be around here Telese is the seventh Long Islander in the past six years to have received a Chick Evans Caddie Scholarship part of a national program that never touched down in Nassau or Suffolk until 2012 having learned about the Evans after his mother did an online financial aid search (she also told relatives about the Long Island Caddie Scholarship and her nephew Nick won one of those) a senior at Glen Cove High School at the time scrambled to get the paperwork done and didn't scramble quickly enough He had to call administrators to get a deadline extension he and his parents had done their homework on the program They learned that the scholarship was established in 1930 by Evans who had started as a caddie and became the first to win the U.S Open in the same year (1916) and later won another U.S Amateur at Engineers Country Club in Roslyn Harbor (1920) and played in the inaugural Walker Cup at the National Golf Links of America in Southampton (1922) Rose Ann and Michael also found out that Evans had a soft spot for caddies and persuaded the Western Golf Association to administer the scholarship that currently is putting 965 caddies through school and has seen 10,600 graduate who once caddied for Evans himself and whose brother Bill made a famous movie about bag-toters Telese learned how wise he was to choose caddying as a summer job when he was a high school sophomore so I called up a bunch of different clubs," he said "Some of the other clubs weren't sure if I could get out 'Come over and you'll get out.' He won the trust of caddie master Mike Hammes and the members "It's so cool to meet so many successful people it's like talking to a family friend," he said Unlike in "Caddyshack," Telese did not have to win a tournament to earn the full ride (although he was captain of the high school golf team) write an essay and withstand an interview in front of 100 people at a Manhattan office "I felt like I could have answered things better it was a great feeling of relief when it was over." Better yet was the feeling two weeks later when he received his acceptance letter He is convinced that caddying is a higher pursuit "It just widens everything," he said you meet so many different types of people with different backgrounds The Newsday app makes it easier to access content without having to log in Unlimited Digital AccessOnly 25¢for 6 months Via Francigena We had a lot of institutional meetings planned during the day so we walked a bit less than we should have and got transported to rush across a few sections surrounded by vineyards and beautiful landscapes As we stopped to fill our water bottles at the fountain a family peaked out of the window and became curious about our big group of hikers; they invited us over to taste some of their grapes – they produce homemade wine so they have just harvested this summer’s growth I am noticing quite a difference between this southern section and the north of Italy in the open unconditional and welcoming attitude of inhabitants of the south and I already see a big difference in the warm welcoming character of people in the north of Italy compared to the Netherlands but then there is yet another huge step between North and South of Italy We crossed the town of Faicchio and then a Roman Bridge over the (dry) river of Titerno Next we entered the town of San Salvatore Telesino with its charming Benedictine Abbey where we were welcomed by the local Pro Loco association Here we visited the Antiquarium of the ancient Roman town of Telesia and its virtually buried amphitheater Our guide told us there is a necropolis in San Salvatore as well they covered it up and keep it underground The Pro Loco organized a refreshment for us outside the Abbey leaving the tarmac section to walk through the green Parco del Grassano we met two Danish ladies who are walking from Formia to Brindisi I’m super happy to finally meet more pilgrims in the Via Francigena del Sud we were welcomed in Telese Terme by the municipality and by the Pro Loco Telesia association which invited us to spend some time soaking in the sulfuric thermal baths of Telese (which have a very strong egg smell but I honestly didn’t enjoy it at all); apparently this water is very beneficial for health and for the skin At the end of the day we visited the exhibition at the Pinacoteca Massimo Rao a local artist who died quite young and was honored by his friends who opened a dedicated museum Tomorrow we will have a rest day in Telese Terme – second to last rest day before our arrival which is quickly getting closer and closer… The warm welcoming vibes of local people in Campania Meeting other pilgrims on the Via Francigena del Sud referent for the Via Francigena del Sud (EAVF) F.A.Q © Associazione Europea delle Vie Francigene | C.F. 91029880340 – P.IVA 02654910344 Powered by ItinerAria Privacy | Cookie Policy  | Legal Notice  © Associazione Europea delle Vie Francigene | C.F Powered by ItinerAria EAVF General Assembly, Pavia (Italy)  |  20 October 2023 This website is using a security service to protect itself from online attacks. The action you just performed triggered the security solution. There are several actions that could trigger this block including submitting a certain word or phrase, a SQL command or malformed data. You can email the site owner to let them know you were blocked. Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page. Notifications can be managed in browser preferences. earned nearly £4k last year from “having fun and making videos” of himself making “food” and smashing it up I would like to be emailed about offers, events and updates from The Independent. Read our Privacy notice A chemistry student has become a TikTok sensation with nearly 4.5 million followers and one billion views after creating amazing illusionist food sculptures from homemade modelling putty has seen his profile explode and is now spending £400 a month on supplies to make his ‘clay’ Mr Telese earned £4,000 last year from “having fun and making videos,” which show him flaunting ‘food’ and smashing it up Devoting up to 35 hours a week to making ultra-realistic food models, ranging from burgers to cakes, using the gloopy putty he calls “slime” – which he creates from glue and bicarbonate of soda – his TikTok is in the top 10 most followed accounts in Italy Mr Telese, of Salerno said: “Getting TikTok was a life-changing moment “I’m just a guy who loves to mix science with art and cuisine and I never expected everything to blow up in the way that it has “I don’t know why my food slimes have been so loved Maybe it’s because they’re so much fun and it’s amazing to watch something that looks like food being destroyed.” seeing all the reactions every single day makes it worth it “My friends say my food slimes are so realistic that they now have trust issues over whether food is real or not!” Splitting his time between studying chemistry and making videos, which he started posting in May 2020 under the account @gtcreationslime and releases every day, he has fans worldwide, with people as far away as South Korea, Tahiti and Indonesia watching them He said: “I started posting constantly from May 2020 and there was a super boom from the second week “I made a video that made me known in Italy, as there was an Italian voiceover, and that’s where it started to take off. “When I started using songs, too, the foreign world started to find my videos, with people in Tahiti and Indonesia watching them. “I still cannot believe people from all over the world are watching my work!” Mr Telese makes his amazing food models by creating each part by hand or with a mould, before painting or dying them with food colouring. He chose to use homemade slime, as it became a craze in 2018, when it was popularised on YouTube as an easy and cheap way for children to create toys. Now he combines his passion for art and science to rustle up his creations, often drawing inspiration from TV shows like MasterChef and Bake Off, where he finds dishes to replicate. He said: “What inspired me to look into food was TV shows about cooking and the concept of unifying science and art in my work really excited me. “The final plate and what you eat – be it a salad, pasta, or a cake – needs to look good as even the eyes want their portion!” While his parents had hoped Mr Telese would devote most of his time to fulfilling a career in chemistry, they have realised that his passion for making slime creations has drawn a huge audience and now wholeheartedly support him. He said: “My parents and my family thought because I was studying chemistry, I would be living a different life and I’d be spending my days doing analysis and wearing a lab coat. “For them, my work with slime has been a bit of a shock, but I have known for a while that this is what I want to do. “I just never expected to blow up so much online.” Reflecting on his sudden rise in popularity, he said he thinks people enjoy the shock factor when he destroys the food and it becomes clear it is just putty. He added: “There is some shock as people always think it’s food, and then I destroy it and in that moment it is left just as slime. “I always get messages from people who thought it was going to be a food recipe and they leave a bit disappointed.” He added: “I read the comments every day and I try to see what people think and what they want to see. “There are many who will get angry when they see it is not food. But for me it means my creations look great.” And Mr Telese is a consummate professional when it comes to his TikTok videos – never switching off and always dreaming up new material. He said: “I commit quite a lot of hours each week to doing this. I never switch off. All I think about is what I can create or recreate. “Even if I am going for a walk if I see an attractive pastry I think about how it can be made using slime. “In the morning and afternoon I will try to film the videos, as there is good sunlight.” He added: “I spend about seven hours a day doing this. It’s a lot of work, but it is fun.” So far, he has produced more than 1,000 slime creations and makes between one and two videos each day. He is also mindful not to leave waste and reuses the slime wherever possible. He said: “My entire one bed apartment is pretty much dedicated to slime. “I have made more than 1,000 slime creations. I make about two videos a day. I publish a video every single day. “And I recycle where possible. What I’m doing really is slimetastic!” Lucie High School is on a precautionary lockdown Friday after the school's principal said a rumor was circulating on social media about a threat to the school principal Nicole Telese emphasized "there is no identified threat." the school is currently on a code yellow lockdown and movement is limited across campus while the rumor is investigated by law enforcement Telese added in her callout that additional security is at the school which is located at 1201 Southeast Jaguar Lane "We place student safety at the highest priority level," Telese said in her call "This matter is being taken very seriously and we are accordingly to ensure a safe campus Anyone found to be making threats will have severe consequences as outlined in the Student Code of Conduct which may include expulsion and/or arrest." Lucie Public Schools said there has not been an actual threat toward the school but rather a rumor of a threat on social media Lucie Police Department said it was made aware on Friday of messages circulating on social media of a school threat that there is "no credible threat at this time." The police department is working closely with St You are using an outdated browser. Upgrade your browser today or install Google Chrome Frame to better experience this site Our mission is to serve each family to the absolute best of our ability along with their friends and to give to the good of our community in which we live and serve.  Email Us 2016Josh Einiger is live with the details.NEW YORK (WABC) -- Keeping planes and the people in them in top shape is always the first priority for an airline the people in charge are faced with an extra set of challenges So what changes when workers have to battle snow and ice Things are now back to normal at JFK Airport after Friday morning's relatively minor snowfall but for the experts who keep you safe in the sky They cleared off any speck of ice or snow that could affect their ability to fly It's a delicate procedure that if done wrong could mean the difference between life and death "We want to make sure that you're safe when you take off and safe when you land and that's our number one priority," said Henry Kuykendall VP of Delta's JFK customer service operations Delta invited Eyewitness News behind the scenes "How I look at it is we're the last line of defense for this aircraft We're the last people to touch this aircraft so we're responsible for it," said Rocky Telese supervisor for Delta's deicing crews at JFK Telese of Long Island demonstrated the deicing process on a 767-400 pressurized alcohol solution eliminates ice and then a second spray down prevents it from reforming They work in the harshest conditions with sometimes anxious passengers "When you look at an airplane and you look at what goes into the deicing process you really kind of have to look at every single passenger that's on that airplane and take that for what it is," said Amar Singh it's going to have to take off in a certain amount of time or else ice could form again the pilots have to come back here and start all over again we watched a team of controllers make sure that wouldn't be necessary they monitor schedules and weather forecasts to try to stay ahead of delays they juggle catering services and bags and cabin crews to get flights back on schedule Delta actually spaces out its departures when it has to deice planes so there are delays that crop up because of that process In 2011, the Tampa native returned home, and brought the Atlanta-based headquarters for the wholesale mortgage lender with him.. "Other lenders only take on higher credit scores," Joseph Pohl, digital marketing specialist, said. "We look at every situation differently." After renting a space for five years, Telese, who grew up in Ybor City, invested 1.6 million in renovating a new home for the headquarters, which he purchased near International Plaza and Bay St. "Tampa Bay has been my and Mr. Telese's home for our entire lives. Both of us grew up here, and went to high school and college in the region," Nicklaus Ball, vice president, said. "We not only like living here, but working here as well. People in this area are dedicated and innovative. That is why we chose to work with all local companies to finance and renovate our new building." Once construction is complete, the new building will encompass a modern look with open ceilings and glass throughout. "We are considering adding a day care because we are very family oriented," Pohl said. A lounge/brainstorming area, which is still a possibility, will give employees a chance to step away from their desks. "We're growing and the new building is to expand. Internally as well," Pohl said. Ball and Pohl also appreciate Tampa's growth. "There is a certain energy to Tampa that is changing with all the plans downtown, and that definitely helps with being able to bring in talented personnel as we plan to double in size in the next three years," Ball said. They moved into the new building on April 17 and will hold a grand opening from 4 p.m. to 7 p.m. on June 1 at 5027 W Laurel St. The grand opening will feature meet and greets, tours and a barbecue. For more information, call (813) 935-1828. SHARE YOUR NEWS: If you have an item for Everybody's Business, contact Arielle Waldman at Awaldman@tampabay.com. 2016 at 4:06 pm ET.css-79elbk{position:relative;}Two new officers were recently welcomed to the Glen Cove Police Department following a unanimous vote by Mayor Reggie Spinello and the Glen Cove City Council Eric Caruso and Kevin Telese will be joining the force in June The two Glen Cove natives are graduates of Glen Cove High School and New York universities They received accolades from the Mayor and City Council members many of whom have known these men and their families since childhood “We are pleased to be in a situation to hire two of Glen Cove’s very own whose skills professional work experience and talents will be an asset to our police department,” Chief William Whitton said upon presenting Glen Cove Police Department badges to Caruso and Telese The two positions became available after James McDonnell and Angelo Telese announced their retirement Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts. the sweet spring waters of Petra served as inspiration for the refurbishment of an ancient Borgo village into this exclusive 43-room resort and spa See more of the Aquapetra Spa It took owner-architect Domenico Tartarone and his wife and interior designer Patrizia Tartarone Cante over ten years to create the vast bath paradise immersed in 26 hectares of oak woodland and organic olive groves Featuring original stone and rock throughout the resort’s gym has been built around existing trees trunks The exterior pool is filled with natural Sannio spring water and the Roman-style bathhouse features a hot and cold pool and sauna are infused with organic mint and rose essences Couples can treat themselves to a hot stone rose oil massage for two in a twin massage booth complete with private suite and plunge pool And after all that indulgence the restaurant beckons with its own temptations offering dishes such as pistachio crusted fillet steak and fresh tomato pizza www.aquapetra.com Receive our daily digest of inspiration, escapism and design stories from around the world direct to your inbox. Melina Keays is the entertaining director of Wallpaper* She has been part of the brand since the magazine’s launch in 1996 and is responsible for entertaining content across the print and digital platforms and for Wallpaper’s creative agency Bespoke Melina takes inspiration from the whole spectrum of art and design – including film Her work for the brand involves curating content and creative direction – conceiving luxury interior landscapes with a focus on food 2018 at 12:48 pm ET.css-79elbk{position:relative;}Glen Cove High School senior Ryan Telese has been awarded the Evans Scholarship a full housing and tuition grant offered to golf caddies Ryan and 16 other students from the East Coast were awarded the scholarships following a final selection interview held at The Union League Club in New York City on Feb Caddies applying for the scholarship had to meet the following criteria: a strong caddie record demonstrated financial need and outstanding character Ryan will attend Penn State University in the fall Principal Antonio Santana and the entire administration at Glen Cove High School extended their congratulations to Ryan Story,Photo courtesy of the Glen Cove City School District: Glen Cove senior Ryan Telese is pictured with guidance counselor Marja Tockman a girl from Texas called Leslie Telese Branson will hear all about the time she went to state Someone will tell her she was one week old when she napped at the Erwin Center in a blue Onesie with a bow with basketballs printed on it tied in her thatch of dark hair She'll learn that she was born on a Friday night in February between basketball games in the Class A Division II girls playoffs up near Abilene coached a game four hours before her baby arrived on the first full day of Leslie Telese's life in basketball was the one that sent Lipan to Austin for the UIL state tournament Lipan sits in that vast stretch of Texas between Fort Worth and Abilene far enough south of Interstate 20 to not be on the way to anything The town of about 400 has seen five girls basketball teams go to state when standout senior Amber Branson played for the Indians Branson ruptured her appendix as a freshman — and started a game 11 days later "She's always been tough," said her father She surprised a lot of strangers when she came to the regional final against Newcastle on Feb "She's a strong woman," said Lipan junior Zully Martinez Branson's decision to coach so soon after the delivery drew much interest said before the state semifinal game Friday afternoon that people not from Lipan have been curious How could a mother leave her newborn to coach a basketball team the next day "People don't understand what basketball's like in Lipan," Les Branson said The Indians lost badly in the state semifinals The shorter Lipan players couldn't break the Neches press They scored four points in the first quarter "I thought my girls did a very good job," Branson said Branson sat on the end of the bench with her other children 7-year-old son Tate and 6-year-old daughter Taylor Taylor and Tate got runner-up medals just like their mom's Their new baby sister was wrapped in a blanket in the second row behind the bench "She was used to this in the womb," Les Branson said Amber Branson and her players tried not to cry "I feel like we're very blessed all the way around from my family at home to my family at school to my family on the floor," she said She added: "I think through this we've gained a whole new light on family." Leslie Telese will know someday what her mother meant by that "I'm going to tell her how proud I am," Branson said Read moreIn an appearance at Boston University Talese was asked to name women writers who inspired him The Post quoted Littlefield as saying: “And then there was a pause and he said And I’ll tell you why.’ And he went into this explanation about how educated women don’t want to hang out with anti-social people.” Amanda Katz, an arts writer for the Boston Globe, wrote on Twitter: “Women don’t write good NF [nonfiction] [because] they don’t feel comfortable talking to strangers, Gay Talese tells largely female journo audience.” Read moreThe author Anubha Bhonsle was also in the audience. Also using Twitter she said Talese was asked “by NBC Washington reporter: scrappy reporters of all ages want to report on murders and scumbags Do you think your comment was in relation to that generation?” I didn’t know women who were doing that at the time Didn't think I'd ever walk out of a Gay Talese talk. Turns out misogyny will do it! #BUnarrative #narrativeBU Talese’s work includes famous pieces on Frank Sinatra and Babe Ruth. The New Journalism involved the combination of literary techniques and journalistic practice in the treatment of nonfiction subjects in which Talese’s work featured with that of Truman Capote The only female authors featured in the collection were Joan Didion and Barbara Goldsmith educated writers want to interview educated people” took a plea bargain from federal prosecutors for a reduced charge of voluntary manslaughter The deal includes a possible 10-year sentence with a credit of two years for time already served Chagolla could be released from prison as early as 2023 the plea deal was very much in Chagolla’s favor rather than Beauty’s "It seems like [Chagolla] made the deal himself," Smith said but he considered Beauty to be "like a brother." The two grew up together raised by their grandfather recounting the grisly details of the murder along with tribal members Larry Telese and Ted Gia were at Gia's house playing cards and drinking Gia's house is on Yavapai-Apache land in a housing unit in the small Chagolla at some point told Telese he would "get that mark," referring to Beauty Chagolla later claimed he was paid $750 to kill Beauty Chagolla blamed Beauty for the death of Gia's girlfriend and told Gia he would "take care of" Beauty that night Englund had died of alcohol poisoning three months earlier according to the Yavapai County Medical Examiner he and Chagolla kicked Beauty while he was down and he recalls that "Beauty did not fight or scream." Chagolla duct-taped Beauty's hands behind his back and retrieved a knife from the kitchen He then repeatedly stabbed Beauty in the neck and shoulder only stopping because the blade broke off in Beauty's head Telese said Chagolla then left the residence “for some time,” then returned with a circular saw and some tools and used the saw and a long knife to cut off Beauty's head leaving "nothing left but a torso." (It's unclear whether Beauty was alive when Chagolla began sawing off his limbs.) Chagolla then asked him to build a fire in his fireplace Chagolla tossed Beauty's hands into the fire and then used pliers to pull out Beauty's teeth Telese told investigators that during the slaughter Chagolla held up Beauty's severed head and yelled "This is what you get for messing with somebody else's girl." He then tossed Beauty's head into the fireplace Telese says Chagolla gathered up the remaining body parts and placed them into the trunk of his car with the help of Gia then returned to tell Gia and Telese that he had "burned" the rest of the arms and legs He also threatened to kill both Gia and Telese if they told anyone about the murder "This is not my first rodeo," Chagolla allegedly bragged to Telese Telese and Chagolla left the house together that night to go out drinking Chagolla's family became suspicious because Chagolla was acting "strange" and had talked about his possible involvement in a murder He posted a cryptic Facebook status update possibly in response to suspicions: "I was just kidding went to the river where he stayed but found only his tent and clothes he's hurting out there somewhere," she recalls Worried family members reported Beauty missing Chagolla’s family discovered something wrapped in a tarp in the trunk of their father’s car that smelled like a "dead animal," according to Chagolla’s father his son then admitted to being involved in a murder and that he had burned body parts in a barrel on the property Because a non-Indian had been accused of murdering a tribal member, on Yavapai Apache reservation land, the FBI led the investigation and the Arizona U.S. Attorney's Office took the case to federal court. Mario Chagolla Jr., took a plea bargain from federal prosecutors for a reduced charge of voluntary manslaughter. Even though Larry Telese and Ted Gia admitted they witnessed the murder, court documents reveal there was no direct evidence that they helped or paid Chagolla to kill Beauty, and no charges were filed against them. In the ensuing investigation, some of Beauty's teeth and burned remains were collected from Gia's fireplace. Remains were also recovered from the burn barrel at the Chagolla residence. "I've had other brothers that died before,” Delbert Smith said. “But going like this—being butchered—it can't be like that. Something has to be done." The 1885 Major Crimes Act further entrenched federal criminal jurisdiction in Indian country by taking away tribal jurisdiction over felonies such as murder, manslaughter, rape, assault, arson, burglary and larceny. These Congressional acts combined give the federal government exclusive jurisdiction, with limited exception, to prosecute and punish crimes committed on reservation lands involving non-Indian perpetrators against Indian victims. But crimes committed by non-Indians against other non-Indians are sometimes subject to state jurisdiction in minor cases and federal jurisdiction in major cases. Due to tribes' politically and legally contentious quasi-sovereign status as "domestic dependent nations" within the U.S., the federal government wields exclusive criminal jurisdiction over most crimes committed in Indian country. In this system, tribes cannot protect tribal members from federal courts. But if a non-Indian commits a crime, like murder, against a tribal member on reservation land, federal courts protect non-Indians from tribal justice systems because tribes have little or no input over federal prosecutions. Chagolla's plea deal was made between his counsel and federal prosecutors, with little or no input from the Yavapai-Apache Nation or Beauty's surviving family. "I think the federal justice system really failed our people here. No protection," Smith said. "It's not a perfect process," admitted Yavapai Apache Police Department (YAPD) Detective Bob Davis, a non-Native and a 13-year veteran on the force. Davis was a detective during the investigation of Dwayne Beauty's murder. The YAPD played a supporting role to the FBI investigators, but the Yavapai-Apache Nation had no bearing on Chagolla's prosecution and sentencing. Davis said collaborations between county, state, tribal and federal agencies are amicable when it comes to investigating and charging crimes committed within Yavapai-Apache jurisdiction; and most YAPD officers have federal, state, and tribal deputization, granting them arrest authority over Indian and non-Indian perpetrators. Yet they have no power over prosecution and sentencing when cases are handed over to the federal system. In a 2011 article on tribal control over federal sentencing, legal scholar Emily Tredeau noted that across the nation profound sentencing inequalities remain between non-Indian and Indian offenders. Non-Indian offenders committing crimes on Indian reservations are sometimes prosecuted outside the federal system in state courts, where convictions may carry lighter sentences. But Indian offenders in Indian country are not allowed this option and are often sentenced to longer prison terms for crimes that would carry much lighter sentences, or none at all, if the crime was committed off-reservation. Tribes, however, have little to no authority over serious crimes—such as homicides—nor are federal prosecutors required to seek tribal input over decisions to decline cases or make plea bargains. "Federal law enforcement bears virtually no political accountability to tribes, which have even less say in the sentences flowing from federal prosecutions," Tredeau's study concluded. Janet Beauty remembered the first time she and her family met with prosecutors from Arizona's U.S. Attorney's Office about her brother's murder. She told prosecutors, "I never want to take a plea agreement." Last June after prosecutors announced to the family they had made a plea agreement, Janet said she was so upset she could hardly speak. "I said, I don't want to [take the plea bargain]. I sat there and I cried and cried and begged them not to take it. It was out of my hands. They took it anyway. "Ten years is a slap in the face," she said. Chagolla's admission of guilt for the murder by taking the plea bargain resolved little for the Beauty family. In fact, it made things worse—Chagolla never revealed what he did with Beauty’s torso. "He's out there somewhere. We never found his torso,” Janet said. “We can't bury him [because] we don't have him. His soul is wandering." Chagolla is scheduled to appear in court this September, where a judge will decide whether to accept the plea bargain or continue with a trial. Will you support our work?All of our content is free And we have hired more Native journalists in the past year than any news organization ─ and with your help we will continue to grow and create career paths for our people Support Indian Country Today for as little as $10 Dr Emilia Telese is an artist and art theorist based between Reykjavík she graduated in Painting from Fine Arts Academy in Florence in 1996 with a particular interest in XIV Century techniques the Italian Trans-AvantGarde movement and contemporary performance and completed her studies in Loughborough in 2021 graduating with a PhD in Social Sciences (Media) Her PhD thesis focused on the social value and the individualisation of artists in the UK between 1980 and 2010.  She has been exhibiting her artwork worldwide since 1994 at major events such as Tate Britain Her art practice involves many traditional media with time based practice interactive and body-responsive technology Emilia has also received awards from several funding bodies since 1999 AHRC (Arts and Humanities Research Council) 2013 at 9:15 am ET.css-79elbk{position:relative;}The Glen Cove Police Department got closer to full strength Tuesday as three new members were approved for hire by the Glen Cove City Council."This seems like a focused group," said Police Chief William Whitton They each have the aptitude to succeed."Peter Michaleas Alexandra Syder and William Telese received well-wishes from Council members as their family members looked on Michaleas and Syder begin eight months of training at the Nassau County Police Academy Monday Telese comes from the New York Police Department and will be trained by Glen Cove Police.Michaleas was formerly a special education teacher in the Locust Valley School District and Syder comes from the business field.Syder will bring the department's number of female officers to two One woman retired in 2012.The hires bring the force's strength to 47 members The department has been low on personnel after 12 retirements in the last year Whitton said the ideal total is between 53 and 55 members but every person we get assists in our day-to-day operations," Whitton said Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page.