RESUMO
COSMIC (http://cancer.sanger.ac.uk) is an expert-curated database of somatic mutations in human cancer. Broad and comprehensive in scope, recent releases in 2016 describe over 4 million coding mutations across all human cancer disease types. Mutations are annotated across the entire genome, but expert curation is focused on over 400 key cancer genes. Now encompassing the majority of molecular mutation mechanisms in oncogenetics, COSMIC additionally describes 10 million non-coding mutations, 1 million copy-number aberrations, 9 million gene-expression variants, and almost 8 million differentially methylated CpGs. This information combines a consistent interpretation of the data from the major cancer genome consortia and cancer genome literature with exhaustive hand curation of over 22,000 gene-specific literature publications. This unit describes the graphical Web site in detail; alternative protocols overview other ways the entire database can be accessed, analyzed, and downloaded. © 2016 by John Wiley & Sons, Inc.
Assuntos
Bases de Dados Genéticas , Mutação/genética , Neoplasias/genética , Oncogenes/genética , Humanos , Anotação de Sequência MolecularRESUMO
[formula: see text] An enantioselective formal total synthesis of roseophilin 3 is presented. The 13-membered ring of macrotricycle 1 was formed via an efficient ring-closing metathesis reaction of bicycle 4. A palladium-catalyzed methoxycarbonylation reaction of enol triflate 5 was utilized to functionalize the right-hand ring of bicycle 2. The allyl substituent was introduced by a radical allylation of alpha-bromoketone 17.
Assuntos
Streptomyces/química , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Pirróis/síntese química , Pirróis/química , EstereoisomerismoRESUMO
In the course of investigations on the possible involvement of the CIEEL (chemically initiated electron-exchange luminescence) mechanism in firefly bioluminescence, we have synthesized two novel firefly luciferin substrate analogues. D-Naphthylluciferin and D-quinolylluciferin were prepared by condensing D-cysteine with 2-cyano-6-hydroxynaphthalene and 2-cyano-6-hydroxyquinoline, respectively. These analogues are the first examples of bioluminescent substrates for firefly luciferase that do not contain a benzothiazole moiety. Firefly luciferase-catalyzed bioluminescence emission spectra revealed that compared to the normal yellow-green light of luciferin (lambda max = 559 nm), the emission from naphthylluciferin is significantly blue-shifted (lambda max = 524 nm); whereas quinolylluciferin emits orange-red light (lambda max = 608 nm). The fluorescence emission spectra, reaction pH optima, relative light yields, light emission kinetics and KM values of the analogues also were measured and compared to those of luciferin. Neither of the analogues produced the characteristic flash kinetics observed for the natural substrate. Instead, slower rise times to peak emission intensity were recorded. It appears that the formation of an intermediate from the analogue adenylates prior to the addition of oxygen is responsible for the slow rise times. The synthetic substrate analogues described here should be useful for future mechanistic studies.
Assuntos
Besouros/metabolismo , Luciferina de Vaga-Lumes/análogos & derivados , Hidroxiquinolinas , Naftóis , Tiazóis , Animais , Luminescência , Análise EspectralRESUMO
X-ray Fluorescence (XRF) Analysis and Atomic Absorption Spectrophotometry (AAS) have been used in assessing heavy metal pollution from some gold mines in Ghana. The presence and levels of heavy metals in gold ore, gold tailings, inland waters, and river sediments have been determined. Using these techniques, the heavy metals: Cr, Mn, Fe, Cu, Zn, As, Pb, Rb, Sr, Y, Zr, and Nb were identified in some of the solid samples within a concentration range of 0.08 ppm--4.9%. However, the inland waters showed the presence of only Fe and Zn at levels of 0.08-2.4 micrograms/mL.
Assuntos
Poluentes Ambientais/análise , Ouro , Metais/análise , Mineração , Poluentes Ambientais/efeitos adversos , Gana , Humanos , Metais/efeitos adversos , Espectrometria por Raios X , Espectrofotometria Atômica , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análiseRESUMO
In this paper the replacement of a lost learning function of rats through a computer-based real-time recording and feedback system is shown. In an experiment two recording electrodes and one stimulation electrode were implanted in an anesthetized rat. During a classical-conditioning paradigm, which includes tone and airpuff stimulation, biosignals were recorded and the stimulation events detected. A computational model of the cerebellum acquired the association between the stimuli and gave feedback to the brain of the rat using deep brain stimulation in order to close the eyelid of the rat. The study shows that replacement of a lost brain function using a direct bidirectional interface to the brain is realizable and can inspire future research for brain rehabilitation.
Assuntos
Comportamento Animal , Piscadela , Reabilitação , Processamento de Sinais Assistido por Computador , Envelhecimento , Animais , Cerebelo/fisiologia , Modelos Teóricos , RatosRESUMO
Catalogue of Somatic Mutations in Cancer (COSMIC) (http://www.sanger.ac.uk/cosmic) is a publicly available resource providing information on somatic mutations implicated in human cancer. Release v51 (January 2011) includes data from just over 19,000 genes, 161,787 coding mutations and 5573 gene fusions, described in more than 577,000 tumour samples. COSMICMart (COSMIC BioMart) provides a flexible way to mine these data and combine somatic mutations with other biological relevant data sets. This article describes the data available in COSMIC along with examples of how to successfully mine and integrate data sets using COSMICMart. DATABASE URL: http://www.sanger.ac.uk/genetics/CGP/cosmic/biomart/martview/.
Assuntos
Mineração de Dados , Bases de Dados Genéticas , Mutação/genética , Neoplasias/genética , Humanos , Ferramenta de BuscaAssuntos
Transformação Celular Neoplásica/diagnóstico , Neoplasias/diagnóstico , Adolescente , Adulto , Antígenos Virais , Autorradiografia , Células Cultivadas , Técnicas de Cultura , Diploide , Feminino , Fibroblastos , Imunofluorescência , Humanos , Cariotipagem , Leucócitos , Métodos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas , Aberrações dos Cromossomos Sexuais , Vírus 40 dos Símios/imunologia , Pele , Estatística como Assunto , Timidina/metabolismo , TrítioAssuntos
Cromossomos Humanos 6-12 e X , Leucócitos/citologia , Lesões Pré-Cancerosas/genética , Cromossomos Sexuais , Doenças Uterinas/genética , Neoplasias Uterinas/genética , Adenocarcinoma/genética , Adulto , Carcinoma/genética , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Cariotipagem , Síndrome do Ovário Policístico/genética , TrítioAssuntos
Aberrações Cromossômicas/patologia , Neutrófilos , Cromatina Sexual , Amenorreia/genética , Autorradiografia , Transtornos Cromossômicos , Citogenética , Displasia Ectodérmica/genética , Feminino , Humanos , Cariometria , Doenças Ovarianas/genética , Síndrome do Ovário Policístico/genética , Timidina , TrítioAssuntos
Aborto Habitual/patologia , Transplante de Pele , Esfregaço Vaginal , Feminino , Humanos , Gravidez , Transplante HomólogoAssuntos
Citogenética , Fibroblastos , Leucócitos , Doença de Paget Extramamária/patologia , Pele/patologia , Vulva/patologia , Neoplasias Vulvares/patologia , Animais , Antígenos , Biópsia , Linhagem Celular , Transformação Celular Neoplásica , Cromossomos Humanos 6-12 e X , Técnicas de Cultura , Feminino , Fibroblastos/microbiologia , Haplorrinos , Humanos , Cariotipagem , Pessoa de Meia-Idade , Doença de Paget Extramamária/imunologia , Poliploidia , Aberrações dos Cromossomos Sexuais , Vírus 40 dos Símios , Transformação Genética , Trítio , Esfregaço Vaginal , Neoplasias Vulvares/imunologiaRESUMO
COSMIC is currently the most comprehensive global resource for information on somatic mutations in human cancer, combining curation of the scientific literature with tumor resequencing data from the Cancer Genome Project at the Sanger Institute, U.K. Almost 4800 genes and 250000 tumors have been examined, resulting in over 50000 mutations available for investigation. This information can be accessed in a number of ways, the most convenient being the Web-based system which allows detailed data mining, presenting the results in easily interpretable formats. This unit describes the graphical system in detail, elaborating an example walkthrough and the many ways that the resulting information can be thoroughly investigated by combining data, respecializing the query, or viewing the results in different ways. Alternate protocols overview the available precompiled data files available for download.
Assuntos
Bases de Dados Genéticas , Mutação , Catálogos como Assunto , Gráficos por Computador , Genética Médica , Humanos , Internet , Neoplasias/classificação , Neoplasias/genética , Oncogenes , FenótipoRESUMO
The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines.
Assuntos
Bases de Dados Genéticas , Internet , Mutação , Neoplasias/genética , HumanosRESUMO
The discovery of mutations in cancer genes has advanced our understanding of cancer. These results are dispersed across the scientific literature and with the availability of the human genome sequence will continue to accrue. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information related to human cancer. To populate this resource, data has currently been extracted from reports in the scientific literature for somatic mutations in four genes, BRAF, HRAS, KRAS2 and NRAS. At present, the database holds information on 66 634 samples and reports a total of 10 647 mutations. Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website.