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INTRODUCTION: Relative Value Units (RVUs) are utilized to measure physician work effort and create national benchmarks. Physicians are often measured against national benchmarks to determine compensation. Using a case study in cytoreductive surgery, we explored variability in coding that can impact national benchmarks. METHODS: A survey was conducted amongst surgeons in the peritoneal surface malignancies consortium (PSM). Data was collected on clinical experience, clinical full time equivalent, wRVUS and institutional coding practice. RESULTS: Coding of the same procedure resulted in significantly varying RVUs (IQR 60-101) across institutions. Higher volume (> 50% practice) appeared to have better coding practices with higher wRVU/case (Median 102 vs 62, p = 0.04). CONCLUSIONS: There is significant variability in the measurement of similar effort across institutions due to coding variability. Such variability creates flaws in measurement necessary for benchmarks.
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Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery.
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BACKGROUND: The use of the robotic approach is increasing for colorectal cancer operations, but the added cost of the platform has the potential to introduce challenges in its dissemination. We hypothesized that adoption of the robot is introducing new disparities in access to minimally invasive surgery (MIS) for colorectal cancer, especially across patient insurance groups. METHODS: This cross-sectional study analyzed surgical cases of stage I-III colorectal cancer from the National Cancer Database (NCDB) between 2010 and 2019. The primary outcome was surgical approach (robotic, laparoscopic, or the composite "MIS"). The predictor was a patient's primary payor. Potential confounders included sociodemographics, tumor characteristics, and the facility. Hierarchical multivariable models were generated, and sensitivity analyses were performed. RESULTS: For colorectal cancer operations, the MIS approach increased from 39% in 2010 to 73% in 2019, driven predominantly by an increase in the robotic approach from 2 to 24%. For laparoscopy, the size of the disparity between patients with Private insurance and Medicaid shrank from 11% (2010) to 4% (2019), whereas this disparity increased for the robotic approach from 1% (2010) to 5% (2019). On adjusted analysis, patients with Medicaid (odds ratio [OR] 0.86 [CI 0.79-0.95]) and the Uninsured (OR 0.67 [CI 0.56-0.79]) had lower odds of receiving a robotic operation than those with Private insurance in 2019. This disparity remained consistent across five sensitivity analyses. CONCLUSIONS: As the field of colorectal cancer surgery shifts away from laparoscopy and toward robotics, new inequities across patient insurance are emerging. Proactive efforts are needed to ensure all patients benefit from a minimally invasive approach.
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Neoplasias Colorretais , Seguro , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Estados Unidos , Humanos , Estudos Transversais , Neoplasias Colorretais/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to assess the accuracy of inpatient postoperative visits assumed in the valuation of surgical relative value units (RVUs). SUMMARY BACKGROUND DATA: Medicare reimburses physicians based on the number of RVUs assigned to a service. For surgical procedures with a 10- or 90-day global period, the RVU valuation is based, in part, on a presumed number of inpatient postoperative visits whether or not those visits occur. The Centers for Medicare and Medicaid Services (CMS) have recently proposed changing all surgical procedures to a 0-day global period. METHODS: We combined 2017 National Surgical Quality Improvement (NSQIP) data with physician time and RVU files from CMS. We then compared the number of inpatient postoperative visits assumed in the valuation to actual length of stay (LOS) information from the surgical registry. RESULTS: The analysis included 10 specialties and 601 distinct current procedural terminology codes. The number of patient observations underlying NSQIP LOS estimates ranged from 50 to 57,904. Eighty-three percent of procedures had median NSQIP LOS values that were shorter than the values assumed in the global period. These differences varied by specialty, with the largest discrepancy in neurosurgery. Procedures in this sample were last reviewed, on average, in 2000, with procedures reviewed more recently having more accurate valuations with respect to LOS. CONCLUSIONS: The number of postoperative visits assumed in the valuation of surgical RVUs is grossly inaccurate. Holding all else equal, removing global periods from surgical RVUs would dramatically reduce surgeon compensation.
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Tempo de Internação/estatística & dados numéricos , Cuidados Pós-Operatórios/estatística & dados numéricos , Escalas de Valor Relativo , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , HumanosRESUMO
OBJECTIVE: The aim of this study was to understand variation in intraoperative and postoperative utilization for common general surgery procedures. SUMMARY BACKGROUND DATA: Reducing surgical costs is paramount to the viability of hospitals. METHODS: Retrospective analysis of electronic health record data for 7762 operations from 2 health systems. Adult patients undergoing laparoscopic cholecystectomy, appendectomy, and inguinal/femoral hernia repair between November 1, 2013 and November 30, 2017 were reviewed for 3 utilization measures: intraoperative disposable supply costs, procedure time, and postoperative length of stay (LOS). Crossed hierarchical regression models were fit to understand case-mixed adjusted variation in utilization across surgeons and locations and to rank surgeons. RESULTS: The number of surgeons performing each type of operation ranged from 20 to 63. The variation explained by surgeons ranged from 8.9% to 38.2% for supply costs, from 15.1% to 54.6% for procedure time, and from 1.3% to 7.0% for postoperative LOS. The variation explained by location ranged from 12.1% to 26.3% for supply costs, from 0.2% to 2.5% for procedure time, and from 0.0% to 31.8% for postoperative LOS. There was a positive correlation (ρ = 0.49, P = 0.03) between surgeons' higher supply costs and longer procedure times for hernia repair, but there was no correlation between other utilization measures for hernia repair and no correlation between any of the utilization measures for laparoscopic appendectomy or cholecystectomy. CONCLUSIONS: Surgeons are significant drivers of variation in surgical supply costs and procedure time, but much less so for postoperative LOS. Intraoperative and postoperative utilization profiles can be generated for individual surgeons and may be an important tool for reducing surgical costs.
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Custos Hospitalares , Cuidados Intraoperatórios/economia , Cuidados Pós-Operatórios/economia , Procedimentos Cirúrgicos Operatórios/economia , Adulto , Idoso , Apendicectomia/economia , California , Colecistectomia Laparoscópica/economia , Controle de Custos , Equipamentos e Provisões Hospitalares/economia , Feminino , Herniorrafia/economia , Humanos , Laparoscopia/economia , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Older adults undergoing surgery are at risk for geriatric events (GEs: delirium, dehydration, falls or fractures, failure to thrive, and pressure ulcers). The prevalence and association of GEs with clinical outcomes after elective surgery is unclear. MATERIALS AND METHODS: Using the 2013-2014 National Inpatient Sample, we analyzed hospital admissions for the five most common elective procedures (total knee arthroplasty, right hemicolectomy, carotid endarterectomy, aortic valve replacement, and radical prostatectomy) in older adults (age ≥ 65). Our primary variable of interest was presence of any GE. Logistic regression estimated the association of GEs with (1) age group and (2) perioperative outcomes (mortality, postoperative complications, prolonged length of stay, and discharge to skilled nursing facility). RESULTS: Of 1,255,120 admissions, 66.5% were aged ≥65. The overall rate of any GE was 2.4% and increased with age (55-64 y: 1.5%; 65-74: 2.2%; ≥75: 4.1%; P < 0.001). After adjustment, the probability of any GE increased with age (P < 0.001). Rates of GEs varied by procedure (P < 0.001). In comparison with admissions with no GEs, one or more GE was associated with higher probability of worse outcomes including mortality, postoperative complications, prolonged length of stay, and discharge to skilled nursing facility (all P < 0.001). In addition, there was a dose-dependent relationship between GEs and these poor perioperative outcomes. CONCLUSIONS: GEs are strongly associated with poor perioperative outcomes. Efforts should focus on mutable factors responsible for GEs to optimize surgical care for older adults.
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Acidentes por Quedas/estatística & dados numéricos , Delírio/epidemiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Insuficiência de Crescimento/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Úlcera por Pressão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hospital-based care accounts for one third of US health spending or over $1 trillion annually, yet a detailed all-payer assessment of what services contribute to this spending is not available. STUDY DESIGN: Cross-sectional and longitudinal evaluation of hospital financial statements from acute-care general hospitals in California between fiscal years 2007 and 2016. The amounts spent on 41 different revenue centers were included. The primary outcome was state-level and hospital-level spending for each revenue center including decomposing growth trends into changes in volume and prices. RESULTS: The analysis included 2941 annual financial statements from 331 hospitals. Between 2007 and 2016, total spending across all centers increased 66.6% from $43.7B to $72.9B. Five centers-surgery and recovery, drugs sold to patients, acute medical/surgical floor, the clinical laboratory, and emergency services-accounted for over 50% of total spending in 2016. Overall spending growths ranged from 1.1%/y (acute pediatrics) to 17.9%/y (observation). Other revenue centers with large increases in spending included emergency services (164.7%), clinics (on-site 114.5%, satellite 129.7%), anesthesia (119.6%), echocardiography (114.4%), and computed tomography (100.8%). Most services had volume growths within ±2%/y, although there were exceptions (eg, observation hours increased 10.0%/y). Prices grew fastest for echocardiograms (10.5%/y), cardiac catheterization (9.7%/y), therapeutic radiology (8.0%/y), and emergency visits (7.5%/y). In general, median prices for services in 2016 were larger than Medicare allowed amounts. CONCLUSIONS: Overall hospital-based spending increased 66.6% between 2007 and 2016 in California, but there was wide variation in spending growth across revenue centers. Understanding this variation-including the relative contributions of volumes and prices-can guide efforts to curb excessive health care spending and optimize resource dedication to current and future patient care needs.
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Preços Hospitalares/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Hospitais Gerais/economia , California , Estudos Transversais , Humanos , Estados UnidosRESUMO
BACKGROUND: Nonoperative management (NOM) of uncomplicated appendicitis has gained recognition as an alternative to surgery. In the largest published randomized trial (Appendicitis Acuta), patients received a 3-d hospital stay for intravenous antibiotics; however, cost implications for health care systems remain unknown. We hypothesized short stay protocols would be cost saving compared with a long stay protocol. MATERIALS AND METHODS: We constructed a Markov model comparing the cost of three protocols for NOM of acute uncomplicated appendicitis: (1) long stay (3-d hospitalization), (2) short stay (1-d hospitalization), and (3) emergency department (ED) discharge. The long stay protocol was modeled on data from the APPAC trial. Model variables were abstracted from national database and literature review. One-way and two-way sensitivity analyses were performed to determine the impact of uncertainty on the model. RESULTS: The long stay treatment protocol had a total 5-y projected cost of $10,735 per patient. The short stay treatment protocol costs $8026 per patient, and the ED discharge protocol costs $6,825, which was $2709 and $3910 less than the long stay protocol, respectively. One-way sensitivity analysis demonstrated that the relative risk of treatment failure with the short stay protocol needed to exceed 6.3 (absolute risk increase of 31%) and with the ED discharge protocol needed to exceed 8.75 (absolute risk increase of 45%) in order for the long stay protocol to become cost saving. CONCLUSIONS: Short duration hospitalization protocols to treat appendicitis nonoperatively with antibiotics are cost saving under almost all model scenarios. Future consideration of patient preferences and health-related quality of life will need to be made to determine if short stay treatment protocols are cost-effective.
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Antibacterianos/administração & dosagem , Apendicite/tratamento farmacológico , Apendicite/terapia , Tratamento Conservador/economia , Redução de Custos/estatística & dados numéricos , Administração Intravenosa , Simulação por Computador , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Análise Custo-Benefício , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Modelos Econômicos , Qualidade de Vida , Fatores de TempoRESUMO
BACKGROUND: Males and females are known to have varied responses to medical interventions. Our study aimed to determine the effect of sex on surgical outcomes after pyloromyotomy. MATERIALS AND METHODS: Using the Kids' Inpatient Database for the years 2003-2012, we performed a serial, cross-sectional analysis of a nationally representative sample of all patients aged <1 y who underwent pyloromyotomy for hypertrophic pyloric stenosis. The primary predictor of interest was sex. Outcomes included mortality, in-hospital complications, cost, and length of stay. Regression models were adjusted by race, age group, comorbidity, complications, and whether operation was performed on the day of admission with region and year fixed effects. RESULTS: Of 48,834 weighted operations, 81.8% were in males and 18.2% were in females. The most common reported race was white (47.3%) and most of the patients were ≥29 days old (72.5%). There was no difference in the odds of postoperative complications, but females had a significantly longer length of stay (incidence rate ratio, 1.28; 95% confidence interval [95% CI], 1.18-1.39; P ≤ 0.01), higher cost (5%, 95% CI, 1.02-1.08; P ≤ 0.01), and higher odds of mortality (odds ratio, 3.26; 95% CI, 1.52-6.98; P ≤ 0.01). CONCLUSIONS: Our study demonstrated that females had worse outcomes after pyloromyotomy compared with males. These findings are striking and are important to consider when treating either sex to help set physician and family expectations perioperatively. Further studies are needed to determine why such differences exist and to develop targeted treatment strategies for both females and males with pyloric stenosis.
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Disparidades nos Níveis de Saúde , Complicações Pós-Operatórias/epidemiologia , Estenose Pilórica Hipertrófica/cirurgia , Piloromiotomia/efeitos adversos , Estudos Transversais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Estenose Pilórica Hipertrófica/economia , Estenose Pilórica Hipertrófica/mortalidade , Estudos Retrospectivos , Fatores SexuaisRESUMO
BACKGROUND: The clinical effectiveness of surgical versus endovascular therapy for chronic limb-threatening ischemia (CLTI) continues to be debated, and the resources required for each therapy are unclear. METHODS: Systematic review of randomized controlled trials (RCTs) and observational studies comparing surgery with endovascular therapy for CLTI, which reported clinical effectiveness and resource utilization. Short-term and long-term clinical outcomes were examined. RESULTS: The search yielded 4,231 titles, of which 17 publications met our inclusion criteria. Five publications were all from 1 RCT, and 12 publications were observational studies. In the RCT, the surgical approach had greater resource use in the first year (total hospital days across all admissions for surgery versus angioplasty: 46.14 ± 53.87 vs. 36.35 ± 51.39; P < 0.001; also true for days in high-dependency and intensive therapy units), but differences were not statistically significant in subsequent years. All-cause mortality presented a nonsignificant difference favoring angioplasty in the first 2 years (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [95% CI], 0.75-2.15), but after 2 years, it favored surgical treatment (aHR, 0.34; 95% CI, 0.17-0.71). The observational studies reported short-term effectiveness and resource utilization favoring endovascular therapy, but most differences were not statistically significant. Long-term outcomes were more mixed; in particular, mortality outcomes generally favored surgery, although concluding that cause and effect is not possible as endovascularly treated patients tended to be older and may have had a shorter life expectancy regardless of therapy. CONCLUSIONS: The clinical effectiveness and resource utilization of surgery compared with endovascular therapy for CLTI is not known with certainty and will not be known until ongoing trials report results. It is likely that findings will vary by the time horizon, where initial outcomes and utilization tend to favor endovascular interventions, but long-term outcomes favor surgical revascularization.
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Angioplastia , Recursos em Saúde , Isquemia/terapia , Doença Arterial Periférica/terapia , Procedimentos Cirúrgicos Vasculares , Idoso , Angioplastia/efeitos adversos , Angioplastia/mortalidade , Doença Crônica , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Tempo de Internação , Masculino , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: Having conquered water surfaces worldwide, the semi-aquatic bugs occupy ponds, streams, lakes, mangroves, and even open oceans. The diversity of this group has inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders our ability to more thoroughly investigate the molecular mechanisms underlying the processes of adaptation and diversification within this group. RESULTS: Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome; the first water strider genome to be sequenced thus far. The size of the G. buenoi genome is approximately 1,000 Mb, and this sequencing effort has recovered 20,949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to a water surface lifestyle. These expansions may affect key processes associated with growth, vision, desiccation resistance, detoxification, olfaction and epigenetic regulation. Strikingly, the G. buenoi genome contains three insulin receptors, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes affecting with opsin genes may be associated with wavelength sensitivity shifts in opsins, which is likely to be key in facilitating specific adaptations in vision for diverse water habitats. CONCLUSIONS: Our findings suggest that local gene duplications might have played an important role during the evolution of water striders. Along with these findings, the sequencing of the G. buenoi genome now provides us the opportunity to pursue exciting research opportunities to further understand the genomic underpinnings of traits associated with the extreme body plan and life history of water striders.
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Genoma , Heterópteros/genética , Heterópteros/fisiologia , Proteínas de Insetos/genética , Adaptação Fisiológica , Animais , Evolução Molecular , Genômica , Heterópteros/classificação , Fenótipo , FilogeniaRESUMO
OBJECTIVE: The aim of this study was to systematically review the risks and benefits of interventions designed to reduce intraoperative costs. SUMMARY BACKGROUND DATA: Episode-based payments shift financial risk from insurers onto hospitals and providers. The operating room (OR) is a resource dense environment and there is growing interest in identifying ways to reduce intraoperative costs while maintaining patient safety. METHODS: We searched PubMed, Cochrane, and CINAHL for articles published between 2001 and March 2017 that assessed interventions designed to reduce intraoperative costs. We grouped interventions into 6 categories: standardization of instruments, switching to reusable instruments or removing instruments from trays, wound closure comparisons, cost feedback to surgeons, head-to-head instrument trials, and timely arrival of surgeon to the OR. RESULTS: Of 43 included studies, 12 were randomized trials and 31 were observational studies. Gross cost estimates ranged from -$413 (losses) to $3154 (savings) per operation, with only 2 studies reporting losses; however, studies had significant methodologic limitations related to cost data. Studies evaluating standardization and cost feedback were the most robust with estimated cost savings between $38 and $732/case, with no change in OR time, length of stay, or adverse events. CONCLUSIONS: Almost all studies assessing interventions to reduce intraoperative costs have demonstrated cost savings with no apparent increase in adverse effects. Methodologic limitations, especially related to cost data, weaken the reliability of these estimates for most intervention categories. However, hospitals seeking to reduce costs may be able to do so safely by standardizing operative instruments or providing cost feedback to surgeons.
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Redução de Custos , Custos Hospitalares/estatística & dados numéricos , Salas Cirúrgicas/economia , Procedimentos Cirúrgicos Operatórios/economia , Análise Custo-Benefício , Humanos , Avaliação de Resultados em Cuidados de Saúde/economia , Segurança do Paciente/economia , Cirurgiões/economia , Instrumentos Cirúrgicos/economia , Estados UnidosRESUMO
Hyalella azteca is a cryptic species complex of epibenthic amphipods of interest to ecotoxicology and evolutionary biology. It is the primary crustacean used in North America for sediment toxicity testing and an emerging model for molecular ecotoxicology. To provide molecular resources for sediment quality assessments and evolutionary studies, we sequenced, assembled, and annotated the genome of the H. azteca U.S. Lab Strain. The genome quality and completeness is comparable with other ecotoxicological model species. Through targeted investigation and use of gene expression data sets of H. azteca exposed to pesticides, metals, and other emerging contaminants, we annotated and characterized the major gene families involved in sequestration, detoxification, oxidative stress, and toxicant response. Our results revealed gene loss related to light sensing, but a large expansion in chemoreceptors, likely underlying sensory shifts necessary in their low light habitats. Gene family expansions were also noted for cytochrome P450 genes, cuticle proteins, ion transporters, and include recent gene duplications in the metal sequestration protein, metallothionein. Mapping of differentially expressed transcripts to the genome significantly increased the ability to functionally annotate toxicant responsive genes. The H. azteca genome will greatly facilitate development of genomic tools for environmental assessments and promote an understanding of how evolution shapes toxicological pathways with implications for environmental and human health.
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Anfípodes , Poluentes Químicos da Água , Animais , Ecotoxicologia , Sedimentos Geológicos , América do Norte , Testes de ToxicidadeRESUMO
Genomes of eusocial insects code for dramatic examples of phenotypic plasticity and social organization. We compared the genomes of seven ants, the honeybee, and various solitary insects to examine whether eusocial lineages share distinct features of genomic organization. Each ant lineage contains â¼4000 novel genes, but only 64 of these genes are conserved among all seven ants. Many gene families have been expanded in ants, notably those involved in chemical communication (e.g., desaturases and odorant receptors). Alignment of the ant genomes revealed reduced purifying selection compared with Drosophila without significantly reduced synteny. Correspondingly, ant genomes exhibit dramatic divergence of noncoding regulatory elements; however, extant conserved regions are enriched for novel noncoding RNAs and transcription factor-binding sites. Comparison of orthologous gene promoters between eusocial and solitary species revealed significant regulatory evolution in both cis (e.g., Creb) and trans (e.g., fork head) for nearly 2000 genes, many of which exhibit phenotypic plasticity. Our results emphasize that genomic changes can occur remarkably fast in ants, because two recently diverged leaf-cutter ant species exhibit faster accumulation of species-specific genes and greater divergence in regulatory elements compared with other ants or Drosophila. Thus, while the "socio-genomes" of ants and the honeybee are broadly characterized by a pervasive pattern of divergence in gene composition and regulation, they preserve lineage-specific regulatory features linked to eusociality. We propose that changes in gene regulation played a key role in the origins of insect eusociality, whereas changes in gene composition were more relevant for lineage-specific eusocial adaptations.
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Formigas/genética , Genoma de Inseto , Animais , Comportamento Animal , Sítios de Ligação , Sequência Conservada , Metilação de DNA , Evolução Molecular , Regulação da Expressão Gênica , Himenópteros/genética , Proteínas de Insetos/genética , MicroRNAs/genética , Modelos Genéticos , Filogenia , Sequências Reguladoras de Ácido Nucleico , Análise de Sequência de DNA , Comportamento Social , Especificidade da Espécie , Sintenia , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: A major role of REST (repressor element-1 silencing transcription factor) is to inhibit the expression of neuronal genes in neural stem cells and non-neuronal cells by binding to a 21 bp consensus sequence and recruiting epigenetic and regulatory cofactors to gene regulatory regions. In neural stem cells, REST silences differentiation-promoting genes to prevent their premature expression and is central to the regulation of neurogenesis and the balance of neural stem cells and neurons. RESULTS: To understand the role of REST in vertebrate neurogenesis, we performed a genome-wide screen for REST targets in Xenopus tropicalis. We identified 742 neuron-restrictive silencer elements (NRSE) associated with 1396 genes that are enriched in neuronal function. Comparative analyses revealed that characteristics of NRSE motifs in frog are similar to those in mammals in terms of the distance to target genes, frequency of motifs and the repertoire of putative target genes. In addition, we identified four F-box ubiquitin ligases as putative REST targets and determined that they are expressed in neuronal tissues during Xenopus development. CONCLUSION: We identified a conserved core of putative target genes in human, mouse and frog that may be fundamental to REST function in vertebrates. We demonstrate that NRSE sites are associated with both protein-coding genes and lncRNAs in the human genome. Furthermore, we demonstrate that REST binding sites are abundant in low gene-occupancy regions of the human genome but this is not due to an increased association with non-coding RNAs. Our findings identify novel targets of REST and broaden the known mechanism of REST-mediated silencing in neurogenesis.
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Genoma , Proteínas Repressoras/metabolismo , Xenopus/genética , Animais , Sequência de Bases , Sítios de Ligação , Proteínas F-Box/química , Proteínas F-Box/metabolismo , Inativação Gênica , Humanos , Hibridização In Situ , Camundongos , Neurogênese/genética , Neurônios/metabolismo , RNA não Traduzido/química , RNA não Traduzido/metabolismo , Proteínas Repressoras/químicaRESUMO
BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.