Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease.

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.

Association Between Traumatic Brain Injury and Psychopathic Traits Among Justice-Involved Adolescents.

Traumatic brain injury (TBI) is a global public health problem and is highly prevalent among justice-involved populations. Pediatric TBI is linked with long-term negative outcomes and is correlated with substance use, criminal behavior, psychiatric disorders, and disruptions in neurocognition. These same TBI correlates are evident among youth with psychopathic traits. Given ongoing neurobiological and social development in adolescence, understanding the link between psychopathic traits and TBI in justice-involved youth is critical. A sample of 263 male adolescents were recruited from a maximum-security juvenile justice facility. Using a structural equation modeling (SEM) framework, measurement invariance of psychopathic traits (TBI ±) was tested, and psychopathy scores were accounted for in terms of TBI variables (severity, age of first TBI, total number), participant's age, IQ, substance use, and internalizing psychopathology. There was evidence of strong invariance across TBI status and those with TBI had higher affective and impulsive lifestyle psychopathic traits than adolescents without TBI. The SEM indicated that TBI severity was associated with lower IQ scores, which in turn were associated with increased lifestyle/antisocial (Factor 2) psychopathic traits. Total number of TBIs was associated with higher substance use, which was associated with both increased interpersonal/affective (Factor 1) and Factor 2 psychopathic traits. These TBI variables also had indirect associations with psychopathic traits through IQ and substance use. The findings indicate that TBI is associated with psychopathic traits and suggest that disturbances in cognition and substance use may be treatment targets for youth with TBI and psychopathic traits.

Integrating depth-dependent protist dynamics and microbial interactions in spring succession of a freshwater reservoir.

BACKGROUND: Protists are essential contributors to eukaryotic diversity and exert profound influence on carbon fluxes and energy transfer in freshwaters. Despite their significance, there is a notable gap in research on protistan dynamics, particularly in the deeper strata of temperate lakes. This study aimed to address this gap by integrating protists into the well-described spring dynamics of Rímov reservoir, Czech Republic. Over a 2-month period covering transition from mixing to established stratification, we collected water samples from three reservoir depths (0.5, 10 and 30 m) with a frequency of up to three times per week. Microbial eukaryotic and prokaryotic communities were analysed using SSU rRNA gene amplicon sequencing and dominant protistan groups were enumerated by Catalysed Reporter Deposition-Fluorescence in situ Hybridization (CARD-FISH). Additionally, we collected samples for water chemistry, phyto- and zooplankton composition analyses. RESULTS: Following the rapid changes in environmental and biotic parameters during spring, protistan and bacterial communities displayed swift transitions from a homogeneous community to distinct strata-specific communities. A prevalence of auto- and mixotrophic protists dominated by cryptophytes was associated with spring algal bloom-specialized bacteria in the epilimnion. In contrast, the meta- and hypolimnion showcased a development of a protist community dominated by putative parasitic Perkinsozoa, detritus or particle-associated ciliates, cercozoans, telonemids and excavate protists (Kinetoplastida), co-occurring with bacteria associated with lake snow. CONCLUSIONS: Our high-resolution sampling matching the typical doubling time of microbes along with the combined microscopic and molecular approach and inclusion of all main components of the microbial food web allowed us to unveil depth-specific populations' successions and interactions in a deep lentic ecosystem.

Chronic traumatic encephalopathy pathognomonic lesions occurring in isolation adjacent to infiltrative and non-infiltrative white matter lesions.

Chronic traumatic encephalopathy (CTE) is defined by perivascular neuronal phosphorylated-tau accumulation at cortical sulcal depths. CTE has been mainly described in the context of repetitive, impact-type traumatic brain injury (rTBI), principally from contact sports. Rarely, CTE has been associated with single TBIs, including in relationship to healed leucotomy sites in brains from formerly institutionalized psychiatric patients without documented rTBI. Given that leucotomy principally involves severing of white matter, this could suggest involvement of axonal injury in CTE pathophysiology. We present three cases wherein isolated CTE pathology was identified adjacent to distinct white matter lesions. Case 1 is a 41-year-old man with history of hereditary hemorrhagic telangiectasia and resection of a cerebral arteriovenous malformation (AVM). Case 2 is a 46-year-old man with glioblastoma. Case 3 is a 52-year-old man with a remote cerebral infarct. Isolated CTE lesions were found adjacent to the aforementioned pathologies in each case. Additional CTE lesions were not identified despite extensive sampling. Multiple age-related tau astrogliopathy (ARTAG)-like lesions were also identified at other sulcal depths near the AVM resection site in Case 1. These cases may provide insights regarding the pathophysiology of the CTE pathognomonic lesion and the development of ARTAG-like pathology adjacent to long-standing mass lesions.

Child-to-Parent Violence and Abuse: A Scoping Review.

Child-to-parent violence and abuse (CPVA) is a pattern of behavior where a parent or carer is abused by a child they are caring for. The main body of work on CPVA is relatively recent and evolving at pace. This scoping review explores the characteristics of parents, carers, children, and young people in cases of CPVA, the characteristics of CPVA, and barriers to and facilitators of help-seeking in cases of CPVA. The scoping review did not exclude any studies on the basis of geographical location or date of the study. The databases Scopus, CINAHL, Web of Science, Medline, and PubMed were searched in August 2023, along with hand searches of key journals. A total of 145 reports were included in the review, selected for their relevance to the scoping review questions. The main findings were: (a) the field of CPVA is rapidly growing, doubling in the last decade but with a predominance of quantitative studies; (b) there is no agreed universal definition; (c) children and young people with disabilities; who identify as trans or nonbinary gender, or who are adopted or fostered, are almost completely absent from the existing research; (d) there is very limited research focusing on protective factors or on help-seeking.

Exploring Alternatives for Marine Toxicity Testing: Initial Evaluation of Fish Embryo and Mysid Tests.

Current regulations require that toxicity assessments be performed using standardized toxicity testing methods, often using fish. Recent legislation in both the European Union and United States has mandated that toxicity testing alternatives implement the 3Rs of animal research (replacement, reduction, and refinement) whenever possible. There have been advances in the development of alternatives for freshwater assessments, but there is a lack of analogous developments for marine assessments. One potential alternative testing method is the fish embryo toxicity (FET) test, which uses fish embryos rather than older fish. In the present study, FET methods were applied to two marine model organisms, the sheepshead minnow and the inland silverside. Another potential alternative is the mysid shrimp survival and growth test, which uses an invertebrate model. The primary objective of the present study was to compare the sensitivity of these three potential alternative testing methods to two standardized fish-based tests using 3,4-dichloroaniline (DCA), a common reference toxicant. A secondary objective was to characterize the ontogeny of sheepshead minnows and inland silversides. This provided a temporal and visual guide that can be used to identify appropriately staged embryos for inclusion in FET tests and delineate key developmental events (e.g., somite development, eyespot formation, etc.). Comparison of the testing strategies for assessing DCA indicated that: (1) the standardized fish tests possessed comparable sensitivity to each other; (2) the mysid shrimp tests possessed comparable sensitivity to the standardized fish tests; (3) the sheepshead minnow and inland silverside FET tests were the least sensitive testing strategies employed; and (4) inclusion of sublethal endpoints (i.e., hatchability and pericardial edema) in the marine FETs increased their sensitivity. Environ Toxicol Chem 2024;43:1285-1299. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Single-molecule chromatin configurations link transcription factor binding to expression in human cells.

The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state, and gene expression levels remain opaque. We applied single-molecule footprinting (SMF) to measure the simultaneous occupancy of TFs, nucleosomes, and components of the transcription machinery on engineered enhancer/promoter constructs with variable numbers of TF binding sites for both a synthetic and an endogenous TF. We find that activation domains enhance a TF's capacity to compete with nucleosomes for binding to DNA in a BAF-dependent manner, TF binding on nucleosome-free DNA is consistent with independent binding between TFs, and average TF occupancy linearly contributes to promoter activation rates. We also decompose TF strength into separable binding and activation terms, which can be tuned and perturbed independently. Finally, we develop thermodynamic and kinetic models that quantitatively predict both the binding microstates observed at the enhancer and subsequent time-dependent gene expression. This work provides a template for quantitative dissection of distinct contributors to gene activation, including the activity of chromatin remodelers, TF activation domains, chromatin acetylation, TF concentration, TF binding affinity, and TF binding site configuration.

Flexible genomic island conservation across freshwater and marine Methylophilaceae.

The evolutionary trajectory of Methylophilaceae includes habitat transitions from freshwater sediments to freshwater and marine pelagial that resulted in genome reduction (genome-streamlining) of the pelagic taxa. However, the extent of genetic similarities in the genomic structure and microdiversity of the two genome-streamlined pelagic lineages (freshwater "Ca. Methylopumilus" and the marine OM43 lineage) has so far never been compared. Here, we analyzed complete genomes of 91 "Ca. Methylopumilus" strains isolated from 14 lakes in Central Europe and 12 coastal marine OM43 strains. The two lineages showed a remarkable niche differentiation with clear species-specific differences in habitat preference and seasonal distribution. On the other hand, we observed a synteny preservation in their genomes by having similar locations and types of flexible genomic islands (fGIs). Three main fGIs were identified: a replacement fGI acting as phage defense, an additive fGI harboring metabolic and resistance-related functions, and a tycheposon containing nitrogen-, thiamine-, and heme-related functions. The fGIs differed in relative abundances in metagenomic datasets suggesting different levels of variability ranging from strain-specific to population-level adaptations. Moreover, variations in one gene seemed to be responsible for different growth at low substrate concentrations and a potential biogeographic separation within one species. Our study provides a first insight into genomic microdiversity of closely related taxa within the family Methylophilaceae and revealed remarkably similar dynamics involving mobile genetic elements and recombination between freshwater and marine family members.

Cognitive and immunological effects of yoga compared to memory training in older women at risk for alzheimer's disease.

Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p < 0.001). At 24-weeks follow-up, KY yielded a significant, large effect size improvement in subjective cognitive impairment measures compared to MET. KYOn a transcriptional level, at 12- and 24-week follow-up, KY uniquely altered aging-associated signatures, including interferon gamma and other psycho-neuro-immune pathways. Levels of chemokine eotaxin-1, an aging marker, increased over time in MET but not KY participants. These results suggest clinical and biological benefits to KY for SCD, linking changes in cognition to the anti-inflammatory effects of yoga.

Sponge-derived matter is assimilated by coral holobionts.

Coral reef biodiversity is maintained by a complex network of nutrient recycling among organisms. Sponges assimilate nutrients produced by other organisms like coral and algae, releasing them as particulate and dissolved matter, but to date, only a single trophic link between sponge-derived dissolved matter and a macroalgae has been identified. We sought to determine if sponge-coral nutrient exchange is reciprocal using a stable isotope 'pulse-chase' experiment to trace the uptake of 13C and 15N sponge-derived matter by the coral holobiont for three coral species (Acropora cervicornis, Orbicella faveolata, and Eunicea flexuosa). Coral holobionts incorporated 2.3-26.8x more 15N than 13C from sponge-derived matter and A. cervicornis incorporated more of both C and N than the other corals. Differential isotopic incorporation among coral species aligns with their ecophysiological characteristics (e.g., morphology, Symbiodiniaceae density). Our results elucidate a recycling pathway on coral reefs that has implications for improving coral aquaculture and management approaches.

Transapical Mitral Valve Replacement: 1-Year Results of the Real-World Tendyne European Experience Registry.

BACKGROUND: Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort. OBJECTIVES: The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry. METHODS: All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year. RESULTS: Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year. CONCLUSIONS: This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335).

Photon-Counting Detector CT Virtual Monoenergetic Images for Coronary Artery Stenosis Quantification: Phantom and In Vivo Evaluation.

BACKGROUND. Calcium blooming causes stenosis overestimation on coronary CTA. OBJECTIVE. The purpose of this article was to evaluate the impact of virtual monoenergetic imaging (VMI) reconstruction level on coronary artery stenosis quantification using photon-counting detector (PCD) CT. METHODS. A phantom containing two custom-made vessels (representing 25% and 50% stenosis) underwent PCD CT acquisitions without and with simulated cardiac motion. A retrospective analysis was performed of 33 patients (seven women, 26 men; mean age, 71.3 ± 9.0 [SD] years; 64 coronary artery stenoses) who underwent coronary CTA by PCD CT followed by invasive coronary angiography (ICA). Scans were reconstructed at nine VMI energy levels (40-140 keV). Percentage diameter stenosis (PDS) was measured, and bias was determined from the ground-truth stenosis percentage in the phantom and ICA-derived quantitative coronary angiography measurements in patients. Extent of blooming artifact was measured in the phantom and in calcified and mixed plaques in patients. RESULTS. In the phantom, PDS decreased for 25% stenosis from 59.9% (40 keV) to 13.4% (140 keV) and for 50% stenosis from 81.6% (40 keV) to 42.3% (140 keV). PDS showed lowest bias for 25% stenosis at 90 keV (bias, 1.4%) and for 50% stenosis at 100 keV (bias, -0.4%). Blooming artifacts decreased for 25% stenosis from 61.5% (40 keV) to 35.4% (140 keV) and for 50% stenosis from 82.7% (40 keV) to 52.1% (140 keV). In patients, PDS for calcified plaque decreased from 70.8% (40 keV) to 57.3% (140 keV), for mixed plaque decreased from 69.8% (40 keV) to 56.3% (140 keV), and for noncalcified plaque was 46.6% at 40 keV and 54.6% at 140 keV. PDS showed lowest bias for calcified plaque at 100 keV (bias, 17.2%), for mixed plaque at 140 keV (bias, 5.0%), and for noncalcified plaque at 40 keV (bias, -0.5%). Blooming artifacts decreased for calcified plaque from 78.4% (40 keV) to 48.6% (140 keV) and for mixed plaque from 73.1% (40 keV) to 44.7% (140 keV). CONCLUSION. For calcified and mixed plaque, stenosis severity measurements and blooming artifacts decreased at increasing VMI reconstruction levels. CLINICAL IMPACT. PCD CT with VMI reconstruction helps overcome current limitations in stenosis quantification on coronary CTA.

Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion.

Plectin, a highly versatile and multifunctional cytolinker, has been implicated in several multisystemic disorders. Most sequence variations in the human plectin gene (PLEC) cause epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), an autosomal recessive skin-blistering disorder associated with progressive muscle weakness. In this study, we performed a comprehensive cell biological analysis of dermal fibroblasts from three different patients with EBS-MD, where PLEC expression analyses revealed preserved mRNA levels in all cases, whereas full-length plectin protein content was significantly reduced or completely absent. Downstream effects of pathogenic PLEC sequence alterations included massive bundling of vimentin intermediate filament networks, including the occurrence of ring-like nuclei-encasing filament bundles, elongated mitochondrial networks, and abnormal nuclear morphologies. We found that essential fibroblast functions such as wound healing, migration, or orientation upon cyclic stretch were significantly impaired in the cells of patients with EBS-MD. Finally, EBS-MD fibroblasts displayed reduced adhesion capacities, which could be attributed to smaller focal adhesion contacts. Our study not only emphasizes plectin's functional role in human skin fibroblasts, it also provides further insights into the understanding of EBS-MD-associated disease mechanisms.

Technology-Facilitated Sexual Violence and Abuse in Low and Middle-Income Countries: A Scoping Review.

Technology-facilitated sexual violence and abuse (TFSVA) is a pervasive phenomenon and a global problem. TFSVA refers to any form of sexual violence, exploitation, or harassment enacted through the misuse of digital technologies. This includes, but is not limited to, image-based sexual abuse, online sexual exploitation and harassment, sextortion, and the non-consensual sharing of sexual images. It has significant and long-lasting psychological, social, financial, and health impacts. TFSVA is on the rise, particularly in low and middle-income countries (LMICs), where there has been an explosion in digital technology overall. This scoping review aimed to identify studies on TFSVA in LMICs to examine its types, impacts, victim-survivor coping strategies, and help-seeking. To identify peer-reviewed literature, six databases were searched: Applied Social Sciences Index & Abstracts, ProQuest, PubMed, Scopus, Star Plus-University of Sheffield library search, and Web of Science. The review included empirical studies published in English between 1996 and 2022, focusing on TFSVA among adults (aged 18+) in LMICs. A total of 14 peer-reviewed studies were included, highlighting that scant empirical research is available on TFSVA in LMICs. This review found several types of TFSVA and their wide-ranging impacts; traditional patriarchal societal norms and values largely shape TFSVA for women in LMICs. It also found more social impacts linked to sociocultural factors. Survivors adopted various coping mechanisms and help-seeking behaviors primarily through informal family support. Studies highlighted the need for effective legislation; pro-victim-survivor policing; strong family support; increasing victim-survivors' knowledge about reporting; and more research.

A vascularized 3D model of the human pancreatic islet forex vivostudy of immune cell-islet interaction.

Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively byßcells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of isletßcells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlyingßcell damage in diabetes rely onin vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing-key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel,ex vivoplatform for studying human islet biology in both health and disease.

Grey matter volume predicts improvement in geriatric depression in response to Tai Chi compared to Health Education.

OBJECTIVES: Geriatric depression (GD) is associated with cognitive impairment and brain atrophy. Tai-Chi-Chih (TCC) is a promising adjunct treatment to antidepressants. We previously found beneficial effects of TCC on resting state connectivity in GD. We now tested the effect of TCC on gray matter volume (GMV) change and the association between baseline GMV and clinical outcome. PARTICIPANTS: Forty-nine participants with GD (>=60 y) underwent antidepressant treatment (38 women). INTERVENTION: Participants completed 3 months of TCC (N = 26) or health and wellness education control (HEW; N = 23). MEASUREMENTS: Depression and anxiety symptoms and MRI scans were acquired at baseline and 3-month follow-up. General linear models (GLMs) tested group-by-time interactions on clinical scores. Freesurfer 6.0 was used to process T1-weighted images and to perform voxel-wise whole-brain GLMs of group on symmetrized percent GMV change, and on the baseline GMV and symptom change association, controlling for baseline symptom severity. Age and sex served as covariates in all models. RESULTS: There were no group differences in baseline demographics or clinical scores, symptom change from baseline to follow-up, or treatment-related GMV change. However, whole-brain analysis revealed that lower baseline GMV in several clusters in the TCC, but not the HEW group, was associated with larger improvements in anxiety. This was similar for right precuneus GMV and depressive symptoms. CONCLUSIONS: While we observed no effect on GMV due to the interventions, baseline regional GMV predicted symptom improvements with TCC but not HEW. Longer trials are needed to investigate the long-term effects of TCC on clinical symptoms and neuroplasticity.

Correction: Winter et al. Z-Disk-Associated Plectin (Isoform 1d): Spatial Arrangement, Interaction Partners, and Role in Filamin C Homeostasis. Cells 2023, 12, 1259.

The authors wish to make the following changes to their paper [...].

Cardiac CT Beyond Coronaries: Focus on Structural Heart Disease.

PURPOSE OF REVIEW: Cardiac computed tomography (CT) is an established non-invasive imaging tool for the assessment of coronary artery disease. Furthermore, it plays a key role in the preinterventional work-up of patients presenting with structural heart disease. RECENT FINDINGS: CT is the gold standard for preprocedural annular assessment, device sizing, risk determination of annular injury, coronary occlusion or left ventricular outflow tract obstruction, calcification visualization and quantification of the target structure, and prediction of a co-planar fluoroscopic angulation for transcatheter interventions in patients with structural heart disease. It is further a key imaging modality in postprocedural assessment for prosthesis thrombosis, degeneration, or endocarditis. CT plays an integral part in the imaging work-up of novel transcatheter therapies for structural heart disease and postprocedural assessment for prosthesis thrombosis or endocarditis. This review provides a comprehensive overview of the key role of CT in the context of structural heart interventions.

Single-cell chromatin state transitions during epigenetic memory formation.

Repressive chromatin modifications are thought to compact chromatin to silence transcription. However, it is unclear how chromatin structure changes during silencing and epigenetic memory formation. We measured gene expression and chromatin structure in single cells after recruitment and release of repressors at a reporter gene. Chromatin structure is heterogeneous, with open and compact conformations present in both active and silent states. Recruitment of repressors associated with epigenetic memory produces chromatin compaction across 10-20 kilobases, while reversible silencing does not cause compaction at this scale. Chromatin compaction is inherited, but changes molecularly over time from histone methylation (H3K9me3) to DNA methylation. The level of compaction at the end of silencing quantitatively predicts epigenetic memory weeks later. Similarly, chromatin compaction at the Nanog locus predicts the degree of stem-cell fate commitment. These findings suggest that the chromatin state across tens of kilobases, beyond the gene itself, is important for epigenetic memory formation.