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1.
Ecol Evol ; 13(7): e10244, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37404700

RESUMO

Global declines in insect abundance are of significant concern. While there is evidence that climate change is contributing to insect declines, we know little of the direct mechanisms responsible for these declines. Male fertility is compromised by increasing temperatures, and the thermal limit to fertility has been implicated as an important factor in the response of insects to climate change. However, climate change is affecting both temperature and hydric conditions, and the effects of water availability on male fertility have rarely been considered. Here we exposed male crickets Teleogryllus oceanicus to either low or high-humidity environments while holding temperature constant. We measured water loss and the expression of both pre- and postmating reproductive traits. Males exposed to a low-humidity environment lost more water than males exposed to a high-humidity environment. A male's cuticular hydrocarbon profile (CHC) did not affect the amount of water lost, and males did not adjust the composition of their CHC profiles in response to hydric conditions. Males exposed to a low-humidity environment were less likely to produce courtship song or produced songs of low quality. Their spermatophores failed to evacuate and their ejaculates contained sperm of reduced viability. The detrimental effects of low-humidity on male reproductive traits will compromise male fertility and population persistence. We argue that limits to insect fertility based on temperature alone are likely to underestimate the true effects of climate change on insect persistence and that the explicit incorporation of water regulation into our modeling will yield more accurate predictions of the effects of climate change on insect declines.

2.
Sci Rep ; 13(1): 2744, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797315

RESUMO

Invasive species eradication campaigns often fail due to stochastic arrival events, unpredictable detectability and incorrect resource allocation. Severe uncertainty in model parameter estimates may skew the eradication policy results. Using info-gap decision theory, this research aims to provide managers with a method to quantify their confidence in realizing successful eradication of particular invasive species within their specified eradication budgets (i.e. allowed eradication cost) in face of information-gaps. The potential introduction of the Asian house gecko Hemidactylus frenatus to Barrow Island, Australia is used as a case study to illustrate the model. Results of this research demonstrate that, more robustness to uncertainty in the model parameters can be earnt by (1) increasing the allowed eradication cost (2) investment in pre-border quarantine and border inspection (i.e. prevention) or (3) investment in post-border detection surveillance. The combination of a post-border spatial dispersal model and info-gap decision theory demonstrates a novel and spatially efficient method for managers to evaluate the robustness of eradication policies for incursion of invasive species with unexpected behaviour. These methods can be used to provide insight into the success of management goals, in particular the eradication of invasive species on islands or in broader mainland areas. These insights will assist in avoiding eradication failure and wasteful budget allocation and labour investment.


Assuntos
Espécies Introduzidas , Lagartos , Animais , Análise Custo-Benefício , Incerteza , Austrália , Políticas
3.
J Exp Biol ; 225(15)2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35848820

RESUMO

The often complex cocktails of hydrocarbon compounds found on the cuticles of insects can serve both naturally and sexually selected functions, contributing to an individual's ability to withstand water loss and attract mating partners. However, whether natural and sexual selection act synergistically or antagonistically on a species' cuticular hydrocarbon (CHC) profile remains unclear. Here, we examined the ontogeny of the CHC profile in a species of cricket, Teleogryllus oceanicus, while manipulating humidity during development. We predicted that juvenile crickets should produce only those compounds that contribute to desiccation resistance, while those compounds contributing specifically to male attractiveness should be produced only at sexual maturity. Further, if attractive CHCs come at a cost to desiccation resistance as predicted by some models of sexual selection, then males reared under low humidity should be constrained to invest less in attractive CHCs. Crickets reared under low humidity produced more long-chain methyl-branched alkanes, alkenes and alkadienes than did crickets reared under high humidity. The abundance of n-alkanes was unaffected by humidity treatment. Sexual dimorphism in the CHC profile was not apparent until adult emergence and became exaggerated 10 days after emergence, when crickets were sexually mature. Males produced more of the same compounds that were increased in both sexes under low humidity, but the humidity treatment did not interact with sex in determining CHC abundance. The data suggest that CHC profiles which protect crickets from desiccation might have synergistic effects on male attractiveness, as there was no evidence to suggest males trade-off a CHC profile produced in response to low humidity for one associated with sexual signalling.


Assuntos
Preferência de Acasalamento Animal , Alcanos , Animais , Feminino , Hidrocarbonetos , Masculino , Caracteres Sexuais , Seleção Sexual
4.
Sci Rep ; 11(1): 22828, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819566

RESUMO

Invasive species can lead to community-level damage to the invaded ecosystem and extinction of native species. Most surveillance systems for the detection of invasive species are developed based on expert assessment, inherently coming with a level of uncertainty. In this research, info-gap decision theory (IGDT) is applied to model and manage such uncertainty. Surveillance of the Asian House Gecko, Hemidactylus frenatus Duméril and Bibron, 1836 on Barrow Island, is used as a case study. Our research provides a novel method for applying IGDT to determine the population threshold ([Formula: see text]) so that the decision can be robust to the deep uncertainty present in model parameters. We further robust-optimize surveillance costs rather than minimize surveillance costs. We demonstrate that increasing the population threshold for detection increases both robustness to the errors in the model parameter estimates, and opportuneness to lower surveillance costs than the accepted maximum budget. This paper provides guidance for decision makers to balance robustness and required surveillance expenditure. IGDT offers a novel method to model and manage the uncertainty prevalent in biodiversity conservation practices and modelling. The method outlined here can be used to design robust surveillance systems for invasive species in a wider context, and to better tackle uncertainty in protection of biodiversity and native species in a cost-effective manner.


Assuntos
Monitoramento Ambiental/economia , Espécies Introduzidas , Lagartos/fisiologia , Animais , Biodiversidade , Orçamentos , Conservação dos Recursos Naturais , Análise Custo-Benefício , Modelos Estatísticos , Densidade Demográfica , Especificidade da Espécie , Incerteza
5.
Oral Dis ; 27(2): 378-387, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32609943

RESUMO

OBJECTIVES: To identify factors which influence the intraoral prevalence of human herpes viruses (HHVs) using mucosal swabs, saliva samples and qPCR analysis. METHODOLOGY: In this cross-sectional observational study, matched saliva and oral swabs were collected from a total of 115 subjects: 70 immunocompetent subjects with no mucosal abnormalities, 22 with mucosal abnormalities and 23 therapeutically immunocompromised individuals. Extracted DNA was analysed by multiplex qPCR for detection and quantification of HHVs 1-6. RESULTS: At least one human herpes virus was detected in 77.1% of immunocompetent individuals with no mucosal abnormalities, with EBV the most commonly detected at 61.4%. HHV-6 was detected in 17.1%, HSV-1 in 4.3% and CMV in 1.1%. Detection was higher in saliva than in oral swabs. There was no detection of HSV-2 or VZV. Neither presence of oral mucosal abnormality nor therapeutic immunocompromise was related to increased detection of human herpes virus. CONCLUSION: Commensal detection rates of EBV are high, and caution in clinical correlation of positive detection is warranted. Commensal CMV rates are low, and detection is likely to be clinically relevant. This study presents a comprehensive commensal detection rate of HHVs 1-6 by qPCR in saliva and swabs.


Assuntos
Infecções por Herpesviridae , Vírus , Estudos Transversais , DNA Viral , Infecções por Herpesviridae/diagnóstico , Humanos , Saliva
6.
J Environ Sci Health B ; 55(9): 820-826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609071

RESUMO

Fumigation is required as an appropriate biosecurity measure to exterminate insect pests in shipping containers. The aim of this study was to determine if ethyl formate (EF) + nitrogen could be safely applied as an in-transit fumigant for containers transported on land and then by sea. In-transit fumigation trials were conducted in four 20 ft shipping containers during a four-day journey in December 2019 in Western Australia. Ethyl formate (90 g m-3) was released with nitrogen into the containers. Ethyl formate concentrations inside the containers and the surrounding environment on the barge were monitored at timed intervals throughout the overnight voyage. This study added new data on in-transit fumigation with ethyl formate + nitrogen via road and has successfully demonstrated safety of in-transit fumigation with ethyl formate + nitrogen via the marine sector. There was no detectable risk to the public, crew members on the barge or workers throughout the journey. In addition, all tested containers were ready to be opened and unloaded with 5-10 minutes aeration or without aeration upon arrival.


Assuntos
Ésteres do Ácido Fórmico/análise , Fumigação/métodos , Nitrogênio/análise , Austrália , Desenho de Equipamento , Navios , Temperatura
7.
Sci Rep ; 9(1): 19339, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852943

RESUMO

Large sea-going passenger vessels can pose a high biosecurity risk. The risk posed by marine species is well documented, but rarely the risk posed by terrestrial arthropods. We conducted the longest running, most extensive monitoring program of terrestrial arthropods undertaken on board a passenger vessel. Surveillance was conducted over a 19-month period on a large passenger (cruise) vessel that originated in the Baltic Sea (Estonia). The vessel was used as an accommodation facility to house workers at Barrow Island (Australia) for 15 months, during which 73,061 terrestrial arthropods (222 species - four non-indigenous (NIS) to Australia) were collected and identified on board. Detection of Tribolium destructor Uytt., a high-risk NIS to Australia, triggered an eradication effort on the vessel. This effort totalled more than 13,700 human hours and included strict biosecurity protocols to ensure that this and other non-indigenous species (NIS) were not spread from the vessel to Barrow Island or mainland Australia. Our data demonstrate that despite the difficulties of biosecurity on large vessels, stringent protocols can stop NIS spreading from vessels, even where vessel-wide eradication is not possible. We highlight the difficulties associated with detecting and eradicating NIS on large vessels and provide the first detailed list of species that inhabit a vessel of this kind.


Assuntos
Artrópodes/fisiologia , Navios , Animais , Austrália , Estônia , Geografia , Ilhas , Oceanos e Mares , Análise de Regressão , Risco , Especificidade da Espécie
8.
Sci Rep ; 9(1): 17052, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745186

RESUMO

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.


Assuntos
Carcinoma Ductal Pancreático/genética , Predisposição Genética para Doença/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Pancreáticas/genética , Neoplasias Hipofisárias/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , DNA Tumoral Circulante/genética , Biologia Computacional/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida , Medicina de Precisão/métodos , Sensibilidade e Especificidade
9.
Mol Cancer Res ; 15(11): 1558-1569, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28751461

RESUMO

Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558-69. ©2017 AACR.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Sequenciamento do Exoma/métodos , Perfilação da Expressão Gênica/métodos , Mutação , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Feminino , Redes Reguladoras de Genes , Humanos , Fator 4 Semelhante a Kruppel , Aprendizado de Máquina , Masculino , RNA não Traduzido/genética , Análise de Sequência de RNA/métodos
10.
Sci Rep ; 7(1): 772, 2017 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-28396608

RESUMO

Barrow Island, north-west coast of Australia, is one of the world's significant conservation areas, harboring marsupials that have become extinct or threatened on mainland Australia as well as a rich diversity of plants and animals, some endemic. Access to construct a Liquefied Natural Gas (LNG) plant, Australia's largest infrastructure development, on the island was conditional on no non-indigenous species (NIS) becoming established. We developed a comprehensive biosecurity system to protect the island's biodiversity. From 2009 to 2015 more than 0.5 million passengers and 12.2 million tonnes of freight were transported to the island under the biosecurity system, requiring 1.5 million hrs of inspections. No establishments of NIS were detected. We made four observations that will assist development of biosecurity systems. Firstly, the frequency of detections of organisms corresponded best to a mixture log-normal distribution including the high number of zero inspections and extreme values involving rare incursions. Secondly, comprehensive knowledge of the island's biota allowed estimation of false positive detections (62% native species). Thirdly, detections at the border did not predict incursions on the island. Fourthly, the workforce detected more than half post-border incursions (59%). Similar approaches can and should be implemented for all areas of significant conservation value.


Assuntos
Conservação dos Recursos Naturais , Ilhas , Austrália , Biodiversidade
11.
United European Gastroenterol J ; 5(1): 13-20, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28405317

RESUMO

BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

12.
Genes (Basel) ; 7(12)2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27983717

RESUMO

Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively.

13.
Ann Surg Oncol ; 23(Suppl 5): 746-754, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27577713

RESUMO

BACKGROUND: Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis. METHODS: Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx)-naïve patients with external validation in a separate cohort of 62 CRTx-naïve patients and 169 patients with advanced-stage disease treated with CRTx. RESULTS: As a novel prognostic biomarker after external validation, CD151 showed promise. Patients exhibiting high levels of CD151 (≥median) had a longer median overall survival than patients with low CD151 tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox-regression model with adjustment for tumor stage [adjusted hazard ratio (aHR), 0.33; 95 % confidence interval (CI), 0.14-0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR, 0.22; 95 % CI, 0.08-0.59; p = 0.003). This effect was not found in the separate cohort of CRTx-exposed patients. CONCLUSION: Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone.


Assuntos
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Junção Esofagogástrica , Expressão Gênica , Tetraspanina 24/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Tetraspanina 24/metabolismo
14.
J Gastroenterol Hepatol ; 30(5): 804-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25612140

RESUMO

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.


Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/diagnóstico , Neoplasias Esofágicas/diagnóstico , Guias de Prática Clínica como Assunto , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Austrália , Esôfago de Barrett/patologia , Esôfago de Barrett/terapia , Biomarcadores Tumorais/análise , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagoscopia , Previsões , Humanos , Fatores de Risco
15.
Ann Surg Oncol ; 22(7): 2431-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25348778

RESUMO

BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.


Assuntos
Adenocarcinoma/metabolismo , Esôfago de Barrett/metabolismo , Catepsina E/sangue , Neoplasias Esofágicas/metabolismo , Esôfago/metabolismo , Metaplasia/metabolismo , Lesões Pré-Cancerosas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/mortalidade , Esôfago de Barrett/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Catepsina E/genética , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaplasia/mortalidade , Metaplasia/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/patologia , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
16.
Epigenetics ; 9(8): 1071-82, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24799664

RESUMO

The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC100526820, is located on chromosome 6, hg19 chr6:163 834 097-163 834 982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC. The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC.


Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/metabolismo , Metilação de DNA , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Adulto , Idoso , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Células CACO-2 , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Estadiamento de Neoplasias , RNA Longo não Codificante/metabolismo
17.
BMC Cancer ; 14: 54, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24485021

RESUMO

BACKGROUND: The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. METHODS: Combined epigenomic methods - activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment - were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). RESULTS: Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in >50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. CONCLUSIONS: This study has characterised a panel of 23 genes that show elevated DNA methylation in >50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética/métodos , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Células HCT116 , Células HT29 , Humanos
18.
Proc Biol Sci ; 278(1721): 3123-8, 2011 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-21367785

RESUMO

Cuticular hydrocarbons provide arthropods with the chemical equivalent of the visually extravagant plumage of birds. Their long chain length, together with the number and variety of positions in which methyl branches and double bonds occur, provide cuticular hydrocarbons with an extraordinary level of information content. Here, we demonstrate phenotypic plasticity in an individual's cuticular hydrocarbon profile. Using solid-phase microextraction, a chemical technique that enables multiple sampling of the same individual, we monitor short-term changes in cuticular hydrocarbon profiles of individual crickets, Teleogryllus oceanicus, in response to a social challenge. We experimentally manipulate the dominance status of males and find that dominant males, on losing fights with other dominant males, change their hydrocarbon profile to more closely resemble that of a subordinate. This result demonstrates that cuticular hydrocarbons can be far more responsive to changes in social dominance than previously realized.


Assuntos
Gryllidae/química , Gryllidae/fisiologia , Hidrocarbonetos/análise , Feromônios/análise , Predomínio Social , Animais , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Fenótipo , Comportamento Sexual Animal , Microextração em Fase Sólida , Austrália Ocidental
19.
Biol Rev Camb Philos Soc ; 86(1): 1-13, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20233168

RESUMO

Males of many species choose their mate according to the female's reproductive status, and there is now increasing evidence that male fitness can depend on this discrimination. However, females will also aim to regulate their mating activity so as to maximize their own fitness. As such, both sexes may attempt to dictate the frequency and timing of female mating, reflecting the potentially different costs of female signaling to both sexes. Here, I review evidence that chemical cues and signals are used widely by males to discriminate between mated and unmated females, and explore the mechanisms by which female odour changes post-mating. There is substantial empirical evidence that mated and unmated females differ in their chemical profile, and that this variation provides males with information on a female's mating status. Although there appears to be large variation among species regarding the mechanisms by which female odour is altered post-mating, the transfer of male substances to females during or subsequent to copulation appear to play a major role. This transfer of substances by males may be part of their strategy to suppress reproduction by competing males, particularly in species where females mate more than once.


Assuntos
Comunicação Animal , Atrativos Sexuais/metabolismo , Comportamento Sexual Animal , Animais , Feminino , Aptidão Genética , Masculino , Reprodução
20.
J Evol Biol ; 23(4): 707-14, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20210834

RESUMO

Sexual dimorphism is thought to result from directional sexual selection acting on male signal traits, with female signal traits given little, if any, attention. Here, we examine male mating preferences in the Australian field cricket, Teleogryllus oceanicus. Using a multivariate selection analysis approach, we found that male preferences have the potential to exert selection on female cuticular hydrocarbons, chemical compounds widely used as sexual signals in insects. In addition to finding both stabilizing and disruptive preference gradients, we also found weak negative directional preference for female cuticular hydrocarbons. We contrast our results with a recent study examining sexual selection via female choice on male T. oceanicus cuticular hydrocarbons and suggest that differences in the form and intensity of sexual selection between the genders may provide part of the net selection differential necessary for the evolution of sexual dimorphism in this species.


Assuntos
Gryllidae/fisiologia , Hidrocarbonetos/química , Hidrocarbonetos/farmacologia , Tegumento Comum/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Feminino , Masculino , Análise de Componente Principal , Comportamento Sexual Animal/fisiologia
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