Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny.

The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa1. However, the irreversible post-mortem degradation2 of ancient DNA has so far limited its recovery-outside permafrost areas-to specimens that are not older than approximately 0.5 million years (Myr)3. By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I4, and suggested the presence of protein residues in fossils of the Cretaceous period5-although with limited phylogenetic use6. In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch7-9, using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)10. Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the clade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck's rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel-which is the hardest tissue in vertebrates11, and is highly abundant in the fossil record-can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation.

Common Features of Environmental Mycobacterium chelonae from Colorado Using Partial and Whole Genomic Sequence Analyses.

Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that cause chronic lung disease in susceptible individuals. While presumed to be ubiquitous in built and natural environments, NTM environmental studies are limited. While environmental sampling campaigns have been performed in geographic areas of high NTM disease burden, NTM species diversity is less defined among areas of lower disease burden like Colorado. In Colorado, metals such as molybdenum have been correlated with increased risk for NTM infection, yet environmental NTM species diversity has not yet been widely studied. Based on prior regression modeling, three areas of predicted high, moderate, and low NTM risk were identified for environmental sampling in Colorado. Ice, plumbing biofilms, and sink tap water samples were collected from publicly accessible freshwater sources. All samples were microbiologically cultured and NTM were identified using partial rpoB gene sequencing. From these samples, areas of moderate risk were more likely to be NTM positive. NTM recovery from ice was more common than recovery from plumbing biofilms or tap water. Overall, nine different NTM species were identified, including clinically important Mycobacterium chelonae. MinION technology was used to whole genome sequence and compare mutational differences between six M. chelonae genomes, representing three environmental isolates from this study and three other M. chelonae isolates from other sources. Drug resistance genes and prophages were common findings among environmentally derived M. chelonae, promoting the need for expanded environmental sampling campaigns to improve our current understanding of NTM species abundance while opening new avenues for improved targeted drug therapies.

Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody.

BACKGROUND: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America. METHODS: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion. RESULTS: A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group. CONCLUSIONS: This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.).

Multi-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer.

The assessment of the expression of programmed cell death ligand-1 (PD-L1) using immunohistochemistry (IHC) has been controversial since its introduction. The methods of assessment and the range of assays and platforms contribute to confusion. Perhaps the most challenging aspect of PD-L1 IHC is the combined positive score (CPS) method of interpretation of IHC results. Although the CPS method is prescribed for more indications than any other PD-L1 scoring system, its reproducibility has never been rigorously assessed. In this study, we collected a series of 108 gastric or gastroesophageal junction cancer cases, stained them using the Food and Drug Administration-approved 22C3 assay, scanned them, and then circulated them to 14 pathologists at 13 institutions for the assessment of interpretative concordance for the CPS system. We found that higher cut points (10 or 20) performed better than a CPS of <1 or >1. We used the Observers Needed to Evaluate Subjective Tests algorithm to assess how the CPS system might perform in the real-world setting and found that the cut points of <1 or >1 showed an overall percent agreement of only 30% among the pathologist raters, with a plateau occurring at 8 raters. The raters performed better at higher cut points. However, the best cut point of <20 versus that of >20 was still disappointing, with a plateau at an overall percent agreement of 70% (at 7 raters). Although there is no ground truth for CPS, we compared the score with quantitative messenger RNA measurement and showed no relationship between the score (at any cut point) and messenger RNA amount. In summary, we showed that CPS shows high subjective variability among pathologist readers and is likely to perform poorly in the real-world setting. This system may be the root cause of the poor specificity and relatively low predictive value of IHC companion diagnostic tests for PD-1 axis therapies that use the CPS system.

Removal of Intraocular Foreign Bodies Using a Modified Flute Needle.

PURPOSE: To describe the construction of a novel intraocular snare and evaluate its effectiveness in intraocular foreign body (IOFB) removal. METHOD: This is a retrospective consecutive case series. Five patients underwent pars plana vitrectomy and IOFB removal using the intraocular snare constructed from modified flute needle. RESULTS: All IOFBs were successfully engaged and removed with the snare on the first attempt. Three of the 5 cases (60%) enjoyed good visual outcome (0.4-1.0) postoperatively. No complication related to the use of the snare was encountered in this case series. CONCLUSION: Intraocular foreign body snare is simple, safe, and effective in IOFB removal.

Endoscopic ultrasound-guided balloon-occluded gastrojejunostomy bypass, duodenal stent or laparoscopic gastrojejunostomy for unresectable malignant gastric outlet obstruction.

OBJECTIVES: Malignant gastric outlet obstruction (GOO) can be relieved by either laparoscopic gastrojejunostomy (LGJ), endoscopic stenting (SEMS) or endoscopic ultrasound-guided gastrojejunostomy (endoscopic ultrasound-guided balloon-occluded gastrojejunostomy bypass; EPASS). This study aimed to compare the outcomes of the three treatment methods. METHODS: This was a retrospective study of patients who suffered from malignant GOO between January 2012 to November 2020 that received either EPASS, LGJ or SEMS. The outcomes included the technical and clinical success, 30-day adverse events and mortality, pre and post stenting GOO scores (GOOSs), stent patency and causes of stent dysfunction. RESULTS: One hundred and fourteen patients were included (30 EPASS, 35 LGJ, 49 SEMS). The technical success of EPASS, LGJ and SEMS were 93.3%, 100%, 100% (P = 0.058) and clinical success rates were 93.3%, 80%, 87.8% (P = 0.276), respectively. Procedural time was longest for the LGJ group (P < 0.001). The EPASS group had the shortest hospital stay (EPASS 1.5 [1-17], LGJ 7 [2-44], SEMS 5 [2-46] days, P < 0.001). EPASS group also had the lowest rates of recurrent obstruction (EPASS 3.3%, LGJ 17.1%, SEMS 36.7%, P = 0.002) and re-intervention (EPASS 3.3%, LGJ 17.1%, SEMS 26.5%, P = 0.031). The 1-month GOOS was highest in the EPASS group (EPASS 3 [1-3], LGJ 3 [0-3], SEMS 2 [0-3], P = 0.028). CONCLUSION: Endoscopic ultrasound-guided gastrojejunostomy was associated with better clinical outcomes then the other two procedures. The procedure may be the best option provided that the expertise is available.

Genomic differentiation and local adaptation on a microgeographic scale in a resident songbird.

Elucidating forces capable of driving species diversification in the face of gene flow remains a key goal in evolutionary biology. Song sparrows, Melospiza melodia, occur as 25 subspecies in diverse habitats across North America, are among the continent's most widespread vertebrate species, and are exemplary of many highly variable species for which the conservation of locally adapted populations may be critical to their range-wide persistence. We focus here on six morphologically distinct subspecies resident in the San Francisco Bay region, including three salt-marsh endemics and three residents in upland and riparian habitats adjacent to the Bay. We used reduced-representation sequencing to generate 2,773 SNPs to explore genetic differentiation, spatial population structure, and demographic history. Clustering separated individuals from each of the six subspecies, indicating subtle differentiation at microgeographic scales. Evidence of limited gene flow and low nucleotide diversity across all six subspecies further supports a hypothesis of isolation among locally adapted populations. We suggest that natural selection for genotypes adapted to salt marsh environments and changes in demography over the past century have acted in concert to drive the patterns of diversification reported here. Our results offer evidence of microgeographic specialization in a highly polytypic bird species long discussed as a model of sympatric speciation and rapid adaptation, and they support the hypothesis that conserving locally adapted populations may be critical to the range-wide persistence of similarly highly variable species.

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Pictorial Urgency Scale: A New Tool for Evaluating Bladder Urgency in Children.

PURPOSE: Bladder fullness and urgency are difficult for some patients to express. We hypothesized that images on a pictorial urgency scale would correlate with International Continence Society standard verbal descriptors and bladder volume. MATERIALS AND METHODS: The study population consisted of 267 toilet trained children with a mean age of 7.2 years and their parents (91 adults). Patients were excluded if they had a history of urinary infection, voiding dysfunction, genitourinary surgery or reflux. Participants were read each of the 4 descriptors and asked to point to an image. Correlation between descriptors and figures was analyzed using a mixed effects proportional odds logistic regression model (aim 1 of study). In addition, 73 children undergoing voiding cystourethrography were asked to point to the images during bladder filling. Correlation between percent of expected capacity and image was analyzed using a linear mixed effects model (aim 2 of study). RESULTS: Correlation between descriptors and images (aim 1) was 0.87 (95% CI 0.84 to 0.89) for all participants, 0.84 (95% CI 0.81 to 0.88) for patients younger than age 6 years and 0.88 (95% CI 0.85 to 0.90) for patients 6 to 17 years old. Sequencing of the images was appropriate for increasing degree of urgency. In 73 children undergoing voiding cystourethrography correlation between image and percent of expected capacity (aim 2) was 0.75 (95% CI 0.67 to 0.81, p <0.001). CONCLUSIONS: Figures on the pictorial urgency scale correlate with standard verbal descriptors and bladder volume. The pictorial scale could be a supplemental tool to improve communication of urgency sensation in younger children.

Urological Outcomes of Myelomeningocele and Lipomeningocele.

PURPOSE OF REVIEW: Spina bifida is caused by incomplete neural tube closure during the first trimester. This condition may lead to bowel and bladder dysfunction as well as truncal weakness and motor anomalies. Presentations vary between myelomeningoceles and lipomeningoceles and may result in different outcomes. This review seeks to explore our current understanding of the variations in outcomes between individuals with myelomeningocele and lipomeningocele. RECENT FINDINGS: Prenatal intervention has become a standard of care for prenatal diagnoses of myelomeningocele and has been shown to reduce shunt placement and improve motor skills. However, urological benefit from early intervention remains to be seen. Early surgical repair, however, may be beneficial for patients with lipomeningocele. Literature on the urological outcomes of patients with myelomeningocele and lipomeningocele is lacking. Further research is needed to better elucidate differences in long-term urological outcomes between these two pathologies.

SagB Glucosaminidase Is a Determinant of Staphylococcus aureus Glycan Chain Length, Antibiotic Susceptibility, and Protein Secretion.

UNLABELLED: The envelope of Staphylococcus aureus is comprised of peptidoglycan and its attached secondary polymers, teichoic acid, capsular polysaccharide, and protein. Peptidoglycan synthesis involves polymerization of lipid II precursors into glycan strands that are cross-linked at wall peptides. It is not clear whether peptidoglycan structure is principally determined during polymerization or whether processive enzymes affect cell wall structure and function, for example, by generating conduits for protein secretion. We show here that S. aureus lacking SagB, a membrane-associated N-acetylglucosaminidase, displays growth and cell-morphological defects caused by the exaggerated length of peptidoglycan strands. SagB cleaves polymerized glycan strands to their physiological length and modulates antibiotic resistance in methicillin-resistant S. aureus (MRSA). Deletion of sagB perturbs protein trafficking into and across the envelope, conferring defects in cell wall anchoring and secretion, as well as aberrant excretion of cytoplasmic proteins. IMPORTANCE: Staphylococcus aureus is thought to secrete proteins across the plasma membrane via the Sec pathway; however, protein transport across the cell wall envelope has heretofore not been studied. We report that S. aureus sagB mutants generate elongated peptidoglycan strands and display defects in protein secretion as well as aberrant excretion of cytoplasmic proteins. These results suggest that the thick peptidoglycan layer of staphylococci presents a barrier for protein secretion and that SagB appears to extend the Sec pathway across the cell wall envelope.

Asynchronous demographic responses to Pleistocene climate change in Eastern Nearctic vertebrates.

Pleistocene climatic cycles altered species distributions in the Eastern Nearctic of North America, yet the degree of congruent demographic response to the Pleistocene among codistributed taxa remains unknown. We use a hierarchical approximate Bayesian computational approach to test if population sizes across lineages of snakes, lizards, turtles, mammals, birds, salamanders and frogs in this region expanded synchronously to Late Pleistocene climate changes. Expansion occurred in 75% of 74 lineages, and of these, population size trajectories across the community were partially synchronous, with coexpansion found in at least 50% of lineages in each taxonomic group. For those taxa expanding outside of these synchronous pulses, factors related to when they entered the community, ecological thresholds or biotic interactions likely condition their timing of response to Pleistocene climate change. Unified timing of population size change across communities in response to Pleistocene climate cycles is likely rare in North America.

Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3.

UNLABELLED: Lipocalin-2 (LCN2) was originally isolated from human neutrophils and termed neutrophil gelatinase-associated lipocalin (NGAL). However, the functions of LCN2 and the cell types that are primarily responsible for LCN2 production remain unclear. To address these issues, hepatocyte-specific Lcn2 knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were responsible for more than 90% of the highly elevated serum LCN2 protein level (∼ 6,000 ng/mL) postinfection and more than 60% post-PHx (∼ 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL-6 receptor or Stat3, a major downstream effector of IL-6, markedly abrogated LCN2 elevation in vivo. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that STAT3 was recruited to the promoter region of the Lcn2 gene upon STAT3 activation by IL-6. CONCLUSION: Hepatocytes are the major cell type responsible for LCN2 production after bacterial infection or PHx, and this response is dependent on IL-6 activation of the STAT3 signaling pathway. Thus, hepatocyte-derived LCN2 plays an important role in inhibiting bacterial infection and promoting liver regeneration.

Urethral recurrence after cystectomy: current preventative measures, diagnosis and management.

To summarise the current literature on the diagnosis and management of urethral recurrence (UR) after radical cystectomy (RC), as UR after RC is rare but associated with high mortality. With the recently increased use of orthotopic bladder substitution and the questionable benefit of prophylactic urethrectomy, identification of patients at high risk of UR, management of the remnant urethra, and treatment of UR become critical questions. A review of the PubMed database from 1980 to 2014 was performed to identify studies evaluating recurrent urothelial cancer of the urethra after RC. The search terms used included 'urethral recurrence', 'cystectomy' or 'cystoprostatectomy'. Selected studies provided information on the type of urinary diversion performed, the incidence of UR, and the time to UR. Incidence of UR after RC ranges from 1% to 8% with most recurrences occurring within the first 2 years after surgery. Increased risk of UR is associated with involvement of the prostate, tumour multifocality, bladder neck involvement, and cutaneous diversion. The median overall survival after UR ranges from 6 to 54 months and the 5-year disease-specific survival after UR is reported to be between zero and 83%. UR remains a relatively rare event. Current literature suggests that urethral wash cytology may be useful in patients with intermediate- to high-risk of recurrence to enable early detection of non-invasive disease, which may be amenable to conservative therapy before urethrectomy.

LytR-CpsA-Psr enzymes as determinants of Bacillus anthracis secondary cell wall polysaccharide assembly.

Bacillus anthracis, the causative agent of anthrax, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. Surface (S)-layer proteins and associated proteins (BSLs) function as chain length determinants and bind to the secondary cell wall polysaccharide (SCWP). In this study, we identified the B. anthracis lcpD mutant, which displays increased chain length and S-layer assembly defects due to diminished SCWP attachment to peptidoglycan. In contrast, the B. anthracis lcpB3 variant displayed reduced cell size and chain length, which could be attributed to increased deposition of BSLs. In other bacteria, LytR-CpsA-Psr (LCP) proteins attach wall teichoic acid (WTA) and polysaccharide capsule to peptidoglycan. B. anthracis does not synthesize these polymers, yet its genome encodes six LCP homologues, which, when expressed in S. aureus, promote WTA attachment. We propose a model whereby B. anthracis LCPs promote attachment of SCWP precursors to discrete locations in the peptidoglycan, enabling BSL assembly and regulated separation of septal peptidoglycan.

The capsular polysaccharide of Staphylococcus aureus is attached to peptidoglycan by the LytR-CpsA-Psr (LCP) family of enzymes.

Envelope biogenesis in bacteria involves synthesis of intermediates that are tethered to the lipid carrier undecaprenol-phosphate. LytR-CpsA-Psr (LCP) enzymes have been proposed to catalyze the transfer of undecaprenol-linked intermediates onto the C6-hydroxyl of MurNAc in peptidoglycan, thereby promoting attachment of wall teichoic acid (WTA) in bacilli and staphylococci and capsular polysaccharides (CPS) in streptococci. S. aureus encodes three lcp enzymes, and a variant lacking all three genes (Δlcp) releases WTA from the bacterial envelope and displays a growth defect. Here, we report that the type 5 capsular polysaccharide (CP5) of Staphylococcus aureus Newman is covalently attached to the glycan strands of peptidoglycan. Cell wall attachment of CP5 is abrogated in the Δlcp variant, a defect that is best complemented via expression of lcpC in trans. CP5 synthesis and peptidoglycan attachment are not impaired in the tagO mutant, suggesting that CP5 synthesis does not involve the GlcNAc-ManNAc linkage unit of WTA and may instead utilize another Wzy-type ligase to assemble undecaprenyl-phosphate intermediates. Thus, LCP enzymes of S. aureus are promiscuous enzymes that attach secondary cell wall polymers with discrete linkage units to peptidoglycan.

Detecting concerted demographic response across community assemblages using hierarchical approximate Bayesian computation.

Methods that integrate population-level sampling from multiple taxa into a single community-level analysis are an essential addition to the comparative phylogeographic toolkit. Detecting how species within communities have demographically tracked each other in space and time is important for understanding the effects of future climate and landscape changes and the resulting acceleration of extinctions, biological invasions, and potential surges in adaptive evolution. Here, we present a statistical framework for such an analysis based on hierarchical approximate Bayesian computation (hABC) with the goal of detecting concerted demographic histories across an ecological assemblage. Our method combines population genetic data sets from multiple taxa into a single analysis to estimate: 1) the proportion of a community sample that demographically expanded in a temporally clustered pulse and 2) when the pulse occurred. To validate the accuracy and utility of this new approach, we use simulation cross-validation experiments and subsequently analyze an empirical data set of 32 avian populations from Australia that are hypothesized to have expanded from smaller refugia populations in the late Pleistocene. The method can accommodate data set heterogeneity such as variability in effective population size, mutation rates, and sample sizes across species and exploits the statistical strength from the simultaneous analysis of multiple species. This hABC framework used in a multitaxa demographic context can increase our understanding of the impact of historical climate change by determining what proportion of the community responded in concert or independently and can be used with a wide variety of comparative phylogeographic data sets as biota-wide DNA barcoding data sets accumulate.

Reorganization of the host epigenome by a viral oncogene.

Adenovirus small e1a oncoprotein causes ~70% reduction in cellular levels of histone H3 lysine 18 acetylation (H3K18ac). It is unclear, however, where this dramatic reduction occurs genome-wide. ChIP-sequencing revealed that by 24 h after expression, e1a erases 95% of H3K18ac peaks in normal, contact-inhibited fibroblasts and replaces them with one-third as many at new genomic locations. The H3K18ac peaks at promoters and intergenic regions of genes with fibroblast-related functions are eliminated after infection, and new H3K18ac peaks are established at promoters of highly induced genes that regulate cell cycling and at new putative enhancers. Strikingly, the regions bound by the retinoblastoma family of proteins in contact-inhibited fibroblasts gain new peaks of H3K18ac in the e1a-expressing cells, including 55% of RB1-bound loci. In contrast, over half of H3K9ac peaks are similarly distributed before and after infection, independently of RB1. The strategic redistribution of H3K18ac by e1a highlights the importance of this modification for transcriptional activation and cellular transformation as well as functional differences between the RB-family member proteins.