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1.
Nat Commun ; 11(1): 2316, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385268

RESUMO

Our early-life environment has a profound influence on developing organs that impacts metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life chemical exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome:environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.

2.
Environ Health Perspect ; 128(1): 17010, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31939706

RESUMO

BACKGROUND: Tributyltin (TBT) is a persistent and bioaccumulative environmental toxicant. Developmental exposure to TBT has been shown to cause fatty liver disease (steatosis), as well as increased adiposity in many species, leading to its characterization as an obesogen. OBJECTIVE: We aimed to determine the long-term effects of developmental TBT exposure on the liver. METHODS: C57BL/6J mice were exposed to a dose of TBT (0.5mg/kg body weight per day; 3.07µM) below the current developmental no observed adverse effect level (NOAEL) via drinking water, or drinking water alone, provided to the dam from preconception through lactation. Sires were exposed during breeding and lactation. Pups from two parity cycles were included in this study. Animals were followed longitudinally, and livers of offspring were analyzed by pathological evaluation, immunohistochemistry, immunoblotting, and RNA sequencing. RESULTS: Developmental exposure to TBT led to increased adiposity and hepatic steatosis at 14 and 20 weeks of age and increased liver adenomas at 45 weeks of age in male offspring. Female offspring displayed increased adiposity as compared with males, but TBT did not lead to an increase in fatty liver or tumor development in female offspring. Liver tumors in male mice were enriched in pathways and gene signatures associated with human and rodent nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). This includes down-regulation of growth hormone receptor (GHR) and of STAT5 signaling, which occurred in response to TBT exposure and preceded liver tumor development. CONCLUSIONS: These data reveal a previously unappreciated ability of TBT to increase risk for liver tumorigenesis in mice in a sex-specific manner. Taken together, these findings provide new insights into how early life environmental exposures contribute to liver disease in adulthood. https://doi.org/10.1289/EHP5414.


Assuntos
Poluentes Ambientais/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Adiposidade , Animais , Humanos , Neoplasias Hepáticas/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Testes de Toxicidade
4.
Clin Cancer Res ; 25(12): 3689-3701, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30846479

RESUMO

PURPOSE: The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets. EXPERIMENTAL DESIGN: We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using in vitro and in vivo models. RESULTS: We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in in vitro, and reduced cell proliferation, EMT, and metastasis in vivo. CONCLUSIONS: Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.

5.
Invest Ophthalmol Vis Sci ; 59(1): 132-143, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29332125

RESUMO

Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/ß-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model. Results: ICG-001 exerted strong antiproliferative activity against UM cells, leading to cell cycle arrest, apoptosis, and inhibition of migration. Global gene expression profiling revealed strong suppression of genes associated with cell cycle proliferation, DNA replication, and G1/S transition. Gene set enrichment analysis revealed that ICG-001 suppressed Wnt, mTOR, and MAPK signaling. Strikingly, ICG-001 suppressed the expression of genes associated with UM aggressiveness, including CDH1, CITED1, EMP1, EMP3, SDCBP, and SPARC. Notably, the transcriptomic footprint of ICG-001, when applied to a UM patient dataset, was associated with better clinical outcome. Lastly, ICG-001 exerted anticancer activity against a UM tumor xenograft in mice. Conclusions: Using in vitro and in vivo experiments, we demonstrate that ICG-001 has strong anticancer activity against UM cells and suppresses transcriptional programs critical for the cancer cell. Our results suggest that ICG-001 holds promise and should be examined further as a novel therapeutic agent for UM.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Genes Neoplásicos/genética , Melanoma/tratamento farmacológico , Neoplasias Experimentais , Pirimidinonas/farmacologia , Neoplasias Uveais/tratamento farmacológico , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Melanoma/genética , Melanoma/metabolismo , Camundongos Nus , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismo
6.
Genome Biol ; 19(1): 2, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29310692

RESUMO

BACKGROUND: Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. RESULTS: Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer. CONCLUSIONS: These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.


Assuntos
Epigênese Genética , Gêmeos Monozigóticos/genética , Ilhas de CpG , DNA/sangue , Metilação de DNA , Genoma Humano , Humanos , Modelos Genéticos , Neoplasias/genética , Gêmeos Dizigóticos
7.
Eur Urol Focus ; 4(6): 907-915, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-28753886

RESUMO

BACKGROUND: The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified. OBJECTIVE: To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS: Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75). RESULTS AND LIMITATIONS: UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study. CONCLUSIONS: To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression. PATIENT SUMMARY: Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.


Assuntos
Carcinoma de Células de Transição/metabolismo , Ácidos Graxos/metabolismo , Fosfolipídeos/metabolismo , Triglicerídeos/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Cromatografia Líquida , Biologia Computacional , Diglicerídeos/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Linfonodos/patologia , Lisofosfolipídeos/metabolismo , Masculino , Espectrometria de Massas , Invasividade Neoplásica , Estadiamento de Neoplasias , Transferases de Grupos Nitrogenados/genética , Transferases de Grupos Nitrogenados/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Fosforilcolina/metabolismo , Análise de Componente Principal , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
8.
JCI Insight ; 2(17)2017 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-28878117

RESUMO

Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling. Mechanistically, we demonstrate Tead1 is a cell-autonomous, direct transcriptional activator of SERCA2a and SR-associated protein phosphatase 1 regulatory subunit, Inhibitor-1 (I-1). Thus, Tead1 deletion led to a decrease in SERCA2a and I-1 transcripts and protein, with a consequent increase in PP1-activity, resulting in accumulation of dephosphorylated phospholamban (Pln) and decreased SERCA2a activity. Global transcriptomal analysis in Tead1-deleted hearts revealed significant changes in mitochondrial and sarcomere-related pathways. Additional studies demonstrated there was a trend for correlation between protein levels of TEAD1 and I-1, and phosphorylation of PLN, in human nonfailing and failing hearts. Furthermore, TEAD1 activity was required to maintain PLN phosphorylation and expression of SERCA2a and I-1 in human induced pluripotent stem cell-derived (iPS-derived) CMs. To our knowledge, taken together, this demonstrates a nonredundant, novel role of Tead1 in maintaining normal adult heart function.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Proteínas de Ligação a DNA/fisiologia , Miócitos Cardíacos/citologia , Fatores de Transcrição/fisiologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/induzido quimicamente , Cardiomiopatia Dilatada/patologia , Proliferação de Células , Proteínas de Ligação a DNA/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Knockout , Miocárdio/enzimologia , Miocárdio/metabolismo , Fosforilação , Proteína Fosfatase 1/metabolismo , Retículo Sarcoplasmático/enzimologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Tamoxifeno/farmacologia , Fatores de Transcrição/genética
9.
Mol Cancer Res ; 15(8): 1017-1028, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28507054

RESUMO

Despite the known importance of androgen receptor (AR) signaling in prostate cancer, the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in prostate cancer cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in prostate cancer. Correspondingly, gene expression signatures of AR activity correlated with SLC1A4 and SLC1A5 mRNA levels in clinical cohorts. Interestingly, MYC, a canonical oncogene in prostate cancer and previously described master regulator of glutamine metabolism, was only a context-dependent regulator of SLC1A4 and SLC1A5 levels, being unable to regulate either transporter in PTEN wild-type cells. In contrast, rapamycin was able to decrease the androgen-mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake and prostate cancer cell growth. Taken together, these data indicate that three well-established oncogenic drivers (AR, MYC, and mTOR) function by converging to collectively increase the expression of glutamine transporters, thereby promoting glutamine uptake and subsequent prostate cancer cell growth.Implications: AR, MYC, and mTOR converge to increase glutamine uptake and metabolism in prostate cancer through increasing the levels of glutamine transporters. Mol Cancer Res; 15(8); 1017-28. ©2017 AACR.


Assuntos
Sistema ASC de Transporte de Aminoácidos/genética , Antígenos de Histocompatibilidade Menor/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Regulação Neoplásica da Expressão Gênica , Glutamina/genética , Glutamina/metabolismo , Humanos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética
10.
Sci Rep ; 6: 38044, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27901079

RESUMO

A six-volt vertically-stacked, high current GaAs photovoltaic power converter (PPC) has been designed and fabricated to produce output power over 1 W under monochromatic illumination. An N++-GaAs/P++-AlGaAs tunnel junctions (TJs) structure has been used for connecting each sub-cell in this vertically-stacked PPC device. The thickness of the each GaAs sub-cell has been derived based on the calculation of absorption depth of photons with a wavelength of 808 nm using absorption coefficient obtained from ellipsometry measurements. The devices were characterized under non-uniform CW laser illumination at 808 nm with incident power up to 4.1 W. A maximum conversion efficiency of 50.2% was achieved at 0.3 W under non-uniform (coupled in optical fiber) monochromatic illumination, dropping to 42.5% at 4.1 W. The operating voltage at the maximum power point is 5.5-6.0 V, depending on the incident laser power, and an output electrical power output of 1.3 W can be extracted at a laser power of 2.9 W and the maximum electrical power output amounts to 1.72 W. The external quantum efficiency (EQE) measurement indicates that the performance of PPC can be further improved by refining the design of the thickness of sub-cells and improving TJs.

11.
Mol Endocrinol ; 30(8): 937-48, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27409825

RESUMO

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities.


Assuntos
Receptores Citoplasmáticos e Nucleares/genética , Receptores de Esteroides/genética , Transcriptoma/genética , Animais , Mineração de Dados , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Receptor de Pregnano X , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição/genética , Xenobióticos/farmacologia
12.
ACS Appl Mater Interfaces ; 7(1): 690-5, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25479245

RESUMO

In high-efficiency GaInP/GaAs double-junction tandem solar cells, GaInP layers play a central role in determining the performance of the solar cells. Therefore, gaining a deeper understanding of the optoelectronic processes in GaInP layers is crucial for improving the energy conversion efficiency of GaInP-based photovoltaic devices. In this work, we firmly show strong dependences of localization and recombination of photogenerated carriers in the top GaInP subcells in the GaInP/GaAs double-junction tandem solar cells on the substrate misorientation angle with excitation intensity- and temperature-dependent photoluminescence (PL). The entire solar cell structures including GaInP layers were grown with metalorganic chemical vapor deposition on GaAs substrates with misorientation angles of 2° (denoted as Sample 2°) and 7° (Sample 7°) off (100) toward (111)B. The PL spectral features of the two top GaInP subcells, as well as their excitation-power and temperature dependences exhibit remarkable variation on the misorientation angle. In Sample 2°, the dominant localization mechanism and luminescence channels are due to the energy potential minima caused by highly ordered atomic domains; In Sample 7°, the main localization and radiative recombination of photogenerated carriers occur in the atomically disordered regions. Our results reveal a more precise picture on the localization and recombination mechanisms of photogenerated carriers in the top GaInP subcells, which could be the crucial factors in controlling the optoelectronic efficiency of the GaInP-based multijunction photovoltaic devices.

13.
Proc Natl Acad Sci U S A ; 111(46): 16448-53, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25368173

RESUMO

Hybridization plays an important role in the evolution of certain groups of organisms, adaptation to their environments, and diversification of their genomes. The evolutionary histories of such groups are reticulate, and methods for reconstructing them are still in their infancy and have limited applicability. We present a maximum likelihood method for inferring reticulate evolutionary histories while accounting simultaneously for incomplete lineage sorting. Additionally, we propose methods for assessing confidence in the amount of reticulation and the topology of the inferred evolutionary history. Our method obtains accurate estimates of reticulate evolutionary histories on simulated datasets. Furthermore, our method provides support for a hypothesis of a reticulate evolutionary history inferred from a set of house mouse (Mus musculus) genomes. As evidence of hybridization in eukaryotic groups accumulates, it is essential to have methods that infer reticulate evolutionary histories. The work we present here allows for such inference and provides a significant step toward putting phylogenetic networks on par with phylogenetic trees as a model of capturing evolutionary relationships.


Assuntos
Simulação por Computador , Evolução Molecular , Funções Verossimilhança , Camundongos/genética , Modelos Genéticos , Filogenia , Algoritmos , Animais , China , Eucariotos/classificação , Eucariotos/genética , Europa (Continente) , Especiação Genética , Haplótipos/genética , Cazaquistão , Camundongos/classificação , Taxa de Mutação , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
14.
Math Biosci ; 228(1): 10-5, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20708021

RESUMO

The construction of a consensus tree to summarize the information of a given set of phylogenetic trees is now routinely a part of many studies in systematic biology. One popular method is the majority-rule consensus tree. In this paper we introduce and characterize a new consensus method that refines the majority-rule tree by adding certain compatible clusters satisfying a simple criterion.


Assuntos
Filogenia , Biologia de Sistemas/métodos , Algoritmos
15.
Algorithms Mol Biol ; 5: 2, 2010 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-20047658

RESUMO

BACKGROUND: Supertree methods combine the phylogenetic information from multiple partially-overlapping trees into a larger phylogenetic tree called a supertree. Several supertree construction methods have been proposed to date, but most of these are not designed with any specific properties in mind. Recently, Cotton and Wilkinson proposed extensions of the majority-rule consensus tree method to the supertree setting that inherit many of the appealing properties of the former. RESULTS: We study a variant of one of Cotton and Wilkinson's methods, called majority-rule (+) supertrees. After proving that a key underlying problem for constructing majority-rule (+) supertrees is NP-hard, we develop a polynomial-size exact integer linear programming formulation of the problem. We then present a data reduction heuristic that identifies smaller subproblems that can be solved independently. While this technique is not guaranteed to produce optimal solutions, it can achieve substantial problem-size reduction. Finally, we report on a computational study of our approach on various real data sets, including the 121-taxon, 7-tree Seabirds data set of Kennedy and Page. CONCLUSIONS: The results indicate that our exact method is computationally feasible for moderately large inputs. For larger inputs, our data reduction heuristic makes it feasible to tackle problems that are well beyond the range of the basic integer programming approach. Comparisons between the results obtained by our heuristic and exact solutions indicate that the heuristic produces good answers. Our results also suggest that the majority-rule (+) approach, in both its basic form and with data reduction, yields biologically meaningful phylogenies.

16.
Syst Biol ; 58(3): 360-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20525590
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