Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 121
Filtrar
1.
Ecol Appl ; 33(2): e2790, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36482050

RESUMO

Free-roaming cats are a conservation concern in many areas but identifying their impacts and developing mitigation strategies requires a robust understanding of their distribution and density patterns. Urban and residential areas may be especially relevant in this process because free-roaming cats are abundant in these anthropogenic landscapes. Here, we estimate the occupancy and density of free-roaming cats in Washington D.C. and relate these metrics to known landscape and social factors. We conducted an extended camera trap survey of public and private spaces across D.C. and analyzed data collected from 1483 camera deployments from 2018 to 2020. We estimated citywide cat distribution by fitting hierarchical occupancy models and further estimated cat abundance using a novel random thinning spatial capture-recapture model that allows for the use of photos that can and cannot be identified to individual. Within this model, we utilized individual covariates that provided identity exclusions between photos of unidentifiable cats with inconsistent coat patterns, thus increasing the precision of abundance estimates. This combined model also allowed for unbiased estimation of density when animals cannot be identified to individual at the same rate as for free-roaming cats whose identifiability depended on their coat characteristics. Cat occupancy and abundance declined with increasing distance from residential areas, an effect that was more pronounced in wealthier neighborhoods. There was noteworthy absence of cats detected in larger public spaces and forests. Realized densities ranged from 0.02 to 1.75 cats/ha in sampled areas, resulting in a district-wide estimate of ~7296 free-roaming cats. Ninety percent of cat detections lacked collars and nearly 35% of known individuals were ear-tipped, indicative of district Trap-Neuter-Return (TNR) programs. These results suggest that we mainly sampled and estimated the unowned cat subpopulation, such that indoor/outdoor housecats were not well represented. The precise estimation of cat population densities is difficult due to the varied behavior of subpopulations within free-roaming cat populations (housecats, stray and feral cats), but our methods provide a first step in establishing citywide baselines to inform data-driven management plans for free-roaming cats in urban environments.


Assuntos
Animais Selvagens , Controle da População , Animais , Gatos , Controle da População/métodos , Inquéritos e Questionários , Densidade Demográfica , Meio Ambiente
2.
J Anim Ecol ; 90(7): 1742-1752, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33837530

RESUMO

Neonicotinoid insecticides are the most widely used class of insecticides in the world and can have both lethal and sub-lethal effects on non-target organisms in agricultural areas. Monarch butterflies Danaus plexippus have experienced dramatic declines in recent decades and, given that a large proportion of milkweed on the landscape grows in agricultural areas, there is concern about the negative effects of neonicotinoids on this non-target insect. In the field, we exposed common milkweed Asclepias syriaca, an obligate host plant of monarch butterflies, to agriculturally realistic levels of clothianidin, a widely used neonicotinoid insecticide. We tested whether this treatment influenced the number of eggs laid and larval survival over 2 years. Milkweeds were transplanted into 60 experimental plots alongside a corn crop planted with a clothianidin seed coat and 60 control plots alongside an untreated corn crop. The number of eggs, larvae at each stage (first to fifth instar), and the presence of other arthropods were recorded weekly from June to the end of August and survival from egg to fifth instar was estimated using a Bayesian state-space statistical model. We counted more eggs in treated plots compared to control plots, suggesting a preference for treated milkweed. The number of plots with arthropods did not differ between treatments, but within treated plots, there was a greater decrease in the number of arthropods throughout the season. There was no evidence that monarchs selected plots with fewer arthropods for oviposition. Larval survival was lower in clothianidin-treated plots compared to control plots. Our results suggest milkweed near clothianidin-treated crops can reduce larval survival of monarch butterflies. While we provide some evidence that clothianidin could also act as an ecological trap for this species, further work is needed to identify additional components of fitness, including individual egg-laying rates and survival beyond the pupal stage. Our findings add to a growing body of evidence that neonicotinoids can negatively affect non-target organisms. ​.


Assuntos
Asclepias , Borboletas , Animais , Teorema de Bayes , Feminino , Larva , Neonicotinoides/toxicidade
3.
Biol Lett ; 15(7): 20190327, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31266418

RESUMO

Insects represent the most diverse and functionally important group of flying migratory animals around the globe, yet their small size makes tracking even large migratory species challenging. We attached miniaturized radio transmitters (less than 300 mg) to monarch butterflies ( Danaus plexippus) and common green darner dragonflies ( Anax junius) and tracked their autumn migratory movements through southern Ontario, Canada and into the United States using an automated array of over 100 telemetry towers. The farthest estimated distance a monarch travelled in a single day was 143 km at a wind-assisted groundspeed of 31 km h-1 (8.7 m s-1) and the farthest estimated distance a green darner travelled in a single day was 122 km with a wind-assisted groundspeed of up to 77 km h-1 (21.5 m s-1). For both species, increased temperature and wind assistance positively influenced the pace of migration, but there was no effect of precipitation. While limitations to tracking such small animals remain, our approach and results represent a fundamental advance in understanding the natural history of insect migration and environmental factors that govern their movements.


Assuntos
Borboletas , Odonatos , Migração Animal , Animais , Insetos , Ontário , Temperatura , Estados Unidos , Vento
4.
Conserv Biol ; 33(5): 1219-1223, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30672033

RESUMO

Current conservation templates prioritize biogeographic regions with high intensity ecosystem values, such as exceptional species richness or threat. Intensity-based targets are an important consideration in global efforts, but they do not capture all available opportunities to conserve ecosystem values, including those that accrue in low intensity over large areas. We assess six globally-significant ecosystem values-intact wilderness, freshwater availability, productive marine environments, breeding habitat for migratory wildlife, soil carbon storage, and latitudinal potential for range shift in the face of climate change-to highlight opportunities for high-impact broadly-distributed contributions to global conservation. Nations can serve as a cohesive block of policy that can profoundly influence conservation outcomes. Contributions to global ecosystem values that exceed what is predicted by a nation's area alone, can give rise to countries with the capacity to act as 'conservation superpowers', such as Canada and Russia. For these conservation superpowers, a relatively small number of national policies can have environmental repercussions for the rest of the world.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Biodiversidade , Canadá , Federação Russa
5.
Ecol Lett ; 21(11): 1670-1680, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30152196

RESUMO

Environmental change induces some wildlife populations to shift from migratory to resident behaviours. Newly formed resident populations could influence the health and behaviour of remaining migrants. We investigated migrant-resident interactions among monarch butterflies and consequences for life history and parasitism. Eastern North American monarchs migrate annually to Mexico, but some now breed year-round on exotic milkweed in the southern US and experience high infection prevalence of protozoan parasites. Using stable isotopes (δ2 H, δ13 C) and cardenolide profiles to estimate natal origins, we show that migrant and resident monarchs overlap during fall and spring migration. Migrants at sites with residents were 13 times more likely to have infections and three times more likely to be reproductive (outside normal breeding season) compared to other migrants. Exotic milkweed might either attract migrants that are already infected or reproductive, or alternatively, induce these states. Increased migrant-resident interactions could affect monarch parasitism, migratory success and long-term conservation.


Assuntos
Migração Animal , Asclepias , Borboletas , Doenças Parasitárias , Animais , Borboletas/parasitologia , Estações do Ano
6.
Conserv Biol ; 32(1): 35-49, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28574183

RESUMO

In 2014, the Fish and Wildlife Service (FWS) and National Marine Fisheries Service announced a new policy interpretation for the U.S. Endangered Species Act (ESA). According to the act, a species must be listed as threatened or endangered if it is determined to be threatened or endangered in a significant portion of its range (SPR). The 2014 policy seeks to provide consistency by establishing that a portion of the range should be considered significant if the associated individuals' "removal would cause the entire species to become endangered or threatened." We reviewed 20 quantitative techniques used to assess whether a portion of a species' range is significant according to the new guidance. Our assessments are based on the 3R criteria-redundancy (i.e., buffering from catastrophe), resiliency (i.e., ability to withstand stochasticity), and representation (i.e., ability to evolve)-that the FWS uses to determine if a species merits listing. We identified data needs for each quantitative technique and considered which methods could be implemented given the data limitations typical of rare species. We also identified proxies for the 3Rs that may be used with limited data. To assess potential data availability, we evaluated 7 example species by accessing data in their species status assessments, which document all the information used during a listing decision. In all species, an SPR could be evaluated with at least one metric for each of the 3Rs robustly or with substantial assumptions. Resiliency assessments appeared most constrained by limited data, and many species lacked information on connectivity between subpopulations, genetic variation, and spatial variability in vital rates. These data gaps will likely make SPR assessments for species with complex life histories or that cross national boundaries difficult. Although we reviewed techniques for the ESA, other countries require identification of significant areas and could benefit from this research.


Assuntos
Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Animais , Peixes , Políticas
7.
Pharmacogenomics J ; 17(6): 521-527, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27549341

RESUMO

Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 postmenopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected 2 h after exemestane dosing at a 1- or 3-month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) single-nucleotide polymorphism (SNP) would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates. CYP3A4*22 was associated with a 54% greater exemestane concentration (P<0.01). Concentration was greater in patients who reported White race, had elevated aminotransferases, renal insufficiency, lower body mass index and had not received chemotherapy (all P<0.05), and CYP3A4*22 maintained significance after adjustment for covariates (P<0.01). These genetic and clinical predictors of exemestane concentration may be useful for treatment individualization in patients with breast cancer.


Assuntos
Androstadienos/sangue , Antineoplásicos/sangue , Neoplasias da Mama/genética , Citocromo P-450 CYP3A/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Feminino , Técnicas de Genotipagem , Humanos , Pessoa de Meia-Idade , Testes Farmacogenômicos , Pós-Menopausa , Medicina de Precisão , Valor Preditivo dos Testes
8.
Glob Chang Biol ; 23(7): 2565-2576, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28045226

RESUMO

Addressing population declines of migratory insects requires linking populations across different portions of the annual cycle and understanding the effects of variation in weather and climate on productivity, recruitment, and patterns of long-distance movement. We used stable H and C isotopes and geospatial modeling to estimate the natal origin of monarch butterflies (Danaus plexippus) in eastern North America using over 1000 monarchs collected over almost four decades at Mexican overwintering colonies. Multinomial regression was used to ascertain which climate-related factors best-predicted temporal variation in natal origin across six breeding regions. The region producing the largest proportion of overwintering monarchs was the US Midwest (mean annual proportion = 0.38; 95% CI: 0.36-0.41) followed by the north-central (0.17; 0.14-0.18), northeast (0.15; 0.11-0.16), northwest (0.12; 0.12-0.16), southwest (0.11; 0.08-0.12), and southeast (0.08; 0.07-0.11) regions. There was no evidence of directional shifts in the relative contributions of different natal regions over time, which suggests these regions are comprising the same relative proportion of the overwintering population in recent years as in the mid-1970s. Instead, interannual variation in the proportion of monarchs from each region covaried with climate, as measured by the Southern Oscillation Index and regional-specific daily maximum temperature and precipitation, which together likely dictate larval development rates and food plant condition. Our results provide the first robust long-term analysis of predictors of the natal origins of monarchs overwintering in Mexico. Conservation efforts on the breeding grounds focused on the Midwest region will likely have the greatest benefit to eastern North American migratory monarchs, but the population will likely remain sensitive to regional and stochastic weather patterns.


Assuntos
Migração Animal , Borboletas , Clima , Animais , México , Reprodução
9.
J Anim Ecol ; 84(1): 155-65, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24903085

RESUMO

Threats to migratory animals can occur at multiple periods of the annual cycle that are separated by thousands of kilometres and span international borders. Populations of the iconic monarch butterfly (Danaus plexippus) of eastern North America have declined over the last 21 years. Three hypotheses have been posed to explain the decline: habitat loss on the overwintering grounds in Mexico, habitat loss on the breeding grounds in the United States and Canada, and extreme weather events. Our objectives were to assess population viability, determine which life stage, season and geographical region are contributing the most to population dynamics and test the three hypotheses that explain the observed population decline. We developed a spatially structured, stochastic and density-dependent periodic projection matrix model that integrates patterns of migratory connectivity and demographic vital rates across the annual cycle. We used perturbation analysis to determine the sensitivity of population abundance to changes in vital rate among life stages, seasons and geographical regions. Next, we compared the singular effects of each threat to the full model where all factors operate concurrently. Finally, we generated predictions to assess the risk of host plant loss as a result of genetically modified crops on current and future monarch butterfly population size and extinction probability. Our year-round population model predicted population declines of 14% and a quasi-extinction probability (<1000 individuals) >5% within a century. Monarch abundance was more than four times more sensitive to perturbations of vital rates on the breeding grounds than on the wintering grounds. Simulations that considered only forest loss or climate change in Mexico predicted higher population sizes compared to milkweed declines on the breeding grounds. Our model predictions also suggest that mitigating the negative effects of genetically modified crops results in higher population size and lower extinction risk. Recent population declines stem from reduction in milkweed host plants in the United States that arise from increasing adoption of genetically modified crops and land-use change, not from climate change or degradation of forest habitats in Mexico. Therefore, reducing the negative effects of host plant loss on the breeding grounds is the top conservation priority to slow or halt future population declines of monarch butterflies in North America.


Assuntos
Migração Animal , Borboletas/fisiologia , Conservação dos Recursos Naturais , Ecossistema , Agricultura/métodos , Animais , Asclepias/crescimento & desenvolvimento , Canadá , Extinção Biológica , Feminino , México , Modelos Biológicos , Dinâmica Populacional , Estações do Ano , Estados Unidos
10.
Br J Cancer ; 111(6): 1241-8, 2014 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-25117820

RESUMO

BACKGROUND: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. METHODS: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. RESULTS: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 × 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4). CONCLUSIONS: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/genética , Glicoproteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab , Biomarcadores , Pressão Sanguínea , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
11.
Pharmacogenomics J ; 14(2): 151-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23629159

RESUMO

Efavirenz increases CYP2C19- and CYP3A-mediated omeprazole metabolism. We hypothesized that CYP2C19 and CYP2B6 genetic polymorphisms influence the extent of induction of omeprazole metabolism by efavirenz. Healthy subjects (n=57) were administered a single 20 mg oral dose of omeprazole on two occasions: with a single 600 mg efavirenz dose; and after a 17-day treatment with efavirenz (600 mg per day). DNA was genotyped for CYP2C19*2, *3 and *17 alleles and CYP2B6*6, *4 and *9 alleles using Taqman assays. Omeprazole, its enantiomers and metabolites were measured by liquid chromatography/tandem mass spectrometry. Our results showed that efavirenz increased omeprazole clearances in all CYP2C19 genotypes in non-stereoselective manner, but the magnitude of induction was genotype dependent. Metabolic ratios of 5-hydroxylation of omeprazole were reduced in extensive and intermediate metabolizers of CYP2C19 (P<0.05). No significant associations were observed between CYP2B6 genotypes and induction by efavirenz on omeprazole metabolism. Our data indicate how interplays between drug interactions and CYP2C19 genetic variations may influence systemic exposure of CYP2C19 substrates.


Assuntos
Benzoxazinas/administração & dosagem , Citocromo P-450 CYP2C19/genética , Interações Medicamentosas/genética , Omeprazol/administração & dosagem , Adulto , Alcinos , Ciclopropanos , Citocromo P-450 CYP3A/genética , Estudos de Associação Genética , Genótipo , Humanos , Hidroxilação , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
12.
Br J Clin Pharmacol ; 78(3): 639-48, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24548191

RESUMO

AIMS: To examine whether initiation of fibrates or statins in sulfonylurea users is associated with hypoglycaemia, and examine in vitro inhibition of cytochrome P450 (CYP) enzymes by statins, fenofibrate and glipizide. METHODS: We used healthcare data to conduct nested case-control studies of serious hypoglycaemia (i.e. resulting in hospital admission or emergency department treatment) in persons taking glipizide or glyburide, and calculated adjusted overall and time-stratified odds ratios (ORs) and 95% confidence intervals (CIs). We also characterized the in vitro inhibition of CYP enzymes by statins, fenofibrate and glipizide using fluorometric CYP450 inhibition assays, and estimated area under the concentration-time curve ratios (AUCRs) for the drug pairs. RESULTS: We found elevated adjusted overall ORs for glyburide-fenofibrate (OR 1.84, 95% CI 1.37, 2.47) and glyburide-gemfibrozil (OR 1.57, 95% CI 1.25, 1.96). The apparent risk did decline over time as might be expected from a pharmacokinetic mechanism. Fenofibrate was a potent in vitro inhibitor of CYP2C19 (IC50 = 0.2 µm) and CYP2B6 (IC50 = 0.7 µm) and a moderate inhibitor of CYP2C9 (IC50 = 9.7 µm). The predicted CYP-based AUCRs for fenofibrate-glyburide and gemfibrozil-glyburide interactions were only 1.09 and 1.04, suggesting that CYP inhibition is unlikely to explain such an interaction. CONCLUSIONS: Use of fenofibrate or gemfibrozil together with glyburide was associated with elevated overall risks of serious hypoglycaemia. CYP inhibition seems unlikely to explain this observation. We speculate that a pharmacodynamic effect of fibrates (e.g. activate peroxisome proliferator-activator receptor alpha) may contribute to these apparent interactions.


Assuntos
Ácidos Fíbricos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipoglicemia/etiologia , Compostos de Sulfonilureia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos de Casos e Controles , Inibidores das Enzimas do Citocromo P-450/efeitos adversos , Inibidores das Enzimas do Citocromo P-450/farmacologia , Interações Medicamentosas , Feminino , Ácidos Fíbricos/farmacologia , Glipizida/efeitos adversos , Glipizida/farmacologia , Glibureto/efeitos adversos , Glibureto/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Farmacoepidemiologia , Compostos de Sulfonilureia/farmacologia , Adulto Jovem
13.
Br J Cancer ; 109(9): 2331-9, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24084768

RESUMO

BACKGROUND: Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy. METHODS: Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment. RESULTS: Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ≥20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed. CONCLUSION: Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Mama/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstadienos/uso terapêutico , Aromatase/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Estrogênios/metabolismo , Feminino , Humanos , Letrozol , Mamografia/métodos , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Estudos Prospectivos , Triazóis/uso terapêutico
14.
Ann Oncol ; 24(7): 1867-1873, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23508821

RESUMO

BACKGROUND: Beyond estrogen receptor (ER), there are no validated predictors for tamoxifen (TAM) efficacy and toxicity. We utilized a genome-wide cell-based model to comprehensively evaluate genetic variants for their contribution to cellular sensitivity to TAM. DESIGN: Our discovery model incorporates multidimensional datasets, including genome-wide genotype, gene expression, and endoxifen-induced cellular growth inhibition in the International HapMap lymphoblastoid cell lines (LCLs). Genome-wide findings were further evaluated in NCI60 cancer cell lines. Gene knock-down experiments were performed in four breast cancer cell lines. Genetic variants identified in the cell-based model were examined in 245 Caucasian breast cancer patients who underwent TAM treatment. RESULTS: We identified seven novel single-nucleotide polymorphisms (SNPs) associated with endoxifen sensitivity through the expression of 10 genes using the genome-wide integrative analysis. All 10 genes identified in LCLs were associated with TAM sensitivity in NCI60 cancer cell lines, including USP7. USP7 knock-down resulted in increasing resistance to TAM in four breast cancer cell lines tested, which is consistent with the finding in LCLs and in the NCI60 cells. Furthermore, we identified SNPs that were associated with TAM-induced toxicities in breast cancer patients, after adjusting for other clinical factors. CONCLUSION: Our work demonstrates the utility of a cell-based model in genome-wide identification of pharmacogenomic markers.


Assuntos
Antineoplásicos Hormonais/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Polimorfismo de Nucleotídeo Único , Tamoxifeno/análogos & derivados , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Ensaios Clínicos como Assunto , Ensaios de Seleção de Medicamentos Antitumorais , Receptor alfa de Estrogênio , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Humanos , RNA Interferente Pequeno/genética , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Peptidase 7 Específica de Ubiquitina
15.
Proc Biol Sci ; 280(1768): 20131087, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-23926146

RESUMO

Insect migration may involve movements over multiple breeding generations at continental scales, resulting in formidable challenges to their conservation and management. Using distribution models generated from citizen scientist occurrence data and stable-carbon and -hydrogen isotope measurements, we tracked multi-generational colonization of the breeding grounds of monarch butterflies (Danaus plexippus) in eastern North America. We found that monarch breeding occurrence was best modelled with geographical and climatic variables resulting in an annual breeding distribution of greater than 12 million km(2) that encompassed 99% occurrence probability. Combining occurrence models with stable isotope measurements to estimate natal origin, we show that butterflies which overwintered in Mexico came from a wide breeding distribution, including southern portions of the range. There was a clear northward progression of monarchs over successive generations from May until August when reproductive butterflies began to change direction and moved south. Fifth-generation individuals breeding in Texas in the late summer/autumn tended to originate from northern breeding areas rather than regions further south. Although the Midwest was the most productive area during the breeding season, monarchs that re-colonized the Midwest were produced largely in Texas, suggesting that conserving breeding habitat in the Midwest alone is insufficient to ensure long-term persistence of the monarch butterfly population in eastern North America.


Assuntos
Migração Animal , Borboletas/fisiologia , Animais , Conservação dos Recursos Naturais , Geografia , América do Norte , Dinâmica Populacional , Reprodução , Estações do Ano
16.
Pharmacogenomics J ; 13(5): 456-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22907730

RESUMO

A genome-wide association (GWA) study of treatment outcomes (response and remission) of selective serotonin reuptake inhibitors (SSRIs) was conducted using 529 subjects with major depressive disorder. While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in the riboflavin kinase (RFK) gene on chromosome 9 was associated with 8-week treatment response (odds ratio (OR)=0.42, P=1.04 × 10⁻6). The rs915120 SNP in the G protein-coupled receptor kinase 5 (GRK5) gene on chromosome 10 was associated with 8-week remission (OR=0.50, P=1.15 × 10⁻5). Both SNPs were shown to influence transcription by a reporter gene assay and to alter nuclear protein binding using an electrophoretic mobility shift assay. This report represents an example of joining functional genomics with traditional GWA study results derived from a GWA analysis of SSRI treatment outcomes. The goal of this analytical strategy is to provide insights into the potential relevance of biologically plausible observed associations.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 9 , Transtorno Depressivo Maior/metabolismo , Feminino , Quinase 5 de Receptor Acoplado a Proteína G/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Masculino , Farmacogenética/métodos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Polimorfismo de Nucleotídeo Único/genética , Serotonina/genética , Serotonina/metabolismo , Transcrição Gênica , Resultado do Tratamento
17.
Oecologia ; 173(3): 827-35, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23681287

RESUMO

A comprehensive understanding of how natural and anthropogenic variation in habitat influences populations requires long-term information on how such variation affects survival and dispersal throughout the annual cycle. Gray jays Perisoreus canadensis are widespread boreal resident passerines that use cached food to survive over the winter and to begin breeding during the late winter. Using multistate capture-recapture analysis, we examined apparent survival and dispersal in relation to habitat quality in a gray jay population over 34 years (1977-2010). Prior evidence suggests that natural variation in habitat quality is driven by the proportion of conifers on territories because of their superior ability to preserve cached food. Although neither adults (>1 year) nor juveniles (<1 year) had higher survival rates on high-conifer territories, both age classes were less likely to leave high-conifer territories and, when they did move, were more likely to disperse to high-conifer territories. In contrast, survival rates were lower on territories that were adjacent to a major highway compared to territories that did not border the highway but there was no evidence for directional dispersal towards or away from highway territories. Our results support the notion that natural variation in habitat quality is driven by the proportion of coniferous trees on territories and provide the first evidence that high-mortality highway habitats can act as an equal-preference ecological trap for birds. Reproductive success, as shown in a previous study, but not survival, is sensitive to natural variation in habitat quality, suggesting that gray jays, despite living in harsh winter conditions, likely favor the allocation of limited resources towards self-maintenance over reproduction.


Assuntos
Distribuição Animal/fisiologia , Ecossistema , Modelos Biológicos , Passeriformes/fisiologia , Animais , Comportamento Alimentar/fisiologia , Funções Verossimilhança , Estudos Longitudinais , Ontário , Reprodução/fisiologia , Estações do Ano , Análise de Sobrevida , Traqueófitas
18.
Front Vet Sci ; 9: 766312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747239

RESUMO

Animal shelters play a vital role for pets, such as transitioning animals between homes, from outdoor communities into homes, caring for unadoptable and community animals, and providing a breadth of veterinary and welfare services. The goal of shelters is to move cats to their appropriate outcome as quickly as possible, which for many animals, is to rehome them as quickly as possible through adoption. Therefore, the ability to identify pre-existing factors, particularly those occurring outside the walls of the shelter, which result in specific outcomes is vital. In this study, we used structural equation modeling to test four hypotheses addressing how to predict cat outcome from a shelter in Washington, D.C. We developed four hypotheses that described how cat outcomes could be predicted, based on four general factors: (1) The characteristics of the cats; (2) The location of origin; (3) The type and date of intake; (4) The length of stay. Using 4 years of data from the Humane Rescue Alliance in Washington, D.C., we found support for each of our hypotheses. Additionally, we tested and found support for a global model, which comprised an amalgamation of our all our predictors. From the global model, we can conclude that many factors are at play in predicting cat outcomes in this shelter and very likely in many others as well. Critically, these factors are interconnected, indicating, for example, that cat characteristics mediate the influence of intake location on outcome type. Furthermore, our study highlights the importance of incorporating influences beyond the shelter when attempting to understand cat outcomes. Therefore, to modify cat outcomes most efficiently, such as increasing adoption probabilities, our results show that efforts may be most effective when incorporating multiple factors.

19.
Front Vet Sci ; 9: 946603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532345

RESUMO

Dogs (Canis lupus familiaris) are one of the most common pets around the world but ownership patterns and human-dog interactions have been changing, particularly in developing nations. We conducted household surveys in Costa Rica to characterize dog ownership, the owned dog population, where dogs were confined at night and in the morning, and behaviors regarding selected dog care issues. We also compared these results to similar questionnaires used in Costa Rica over the past 20 years. We found 76% of households in Costa Rica owned at least one dog and on average there were about 1.4 dogs owned per household. These dog ownership rates are higher than previous estimates. The probability of owning a dog was highest on farms and lowest in single family dwellings without a yard, higher among respondents that owned their homes and decreasing with increasing human population density The total number of owned dogs in Costa Rica was estimated to be 2,222,032 (95% confidence intervals: 1,981,497-2,503,751). The sterilization rate for homed dogs in 2020 was approximately 62% (females: 67%, males: 61%) which is higher than the 18% of owned dogs that were sterilized in a 2003 survey. Overall, only 1.2% (95% CI: 0.3-2.5%) of owned dogs slept on the street with a slightly higher proportion on the street at 8 am. The number of owned dogs roaming the streets at night nation-wide was estimated to be 27,208 (95% CI: 7,557-56,619) compared to 43,142 (95% CI: 20,118-73,618) on the street at 8 am. The number of unowned free-roaming dogs in Costa Rica has never been estimated but we can generate some idea of the size of the unowned dog population by determining the proportion of free-roaming dogs on the street wearing collars. There was a negative relationship between human population density and owned dogs being on the street meaning fewer dogs roam the streets in highly populated areas compared to less populated areas. Overall, we identify trends against which future progress can be measured and provide information that are critical in designing effective humane dog management programs in Costa Rica in the future.

20.
Climacteric ; 14(1): 171-80, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20450413

RESUMO

OBJECTIVES: To evaluate the relationships among measures of hot flushes, perceived hot flush interference, sleep disturbance, and measures of quality of life while controlling for potential covariates (patient and treatment variables). METHODS: Breast cancer survivors (n = 395) due to receive aromatase inhibitor therapy provided demographic information, physiological hot flush data via sternal skin conductance monitoring, hot flush frequency via written diary and electronic event marker, hot flush severity and bother via written diary, and questionnaire data via the Hot Flash Related Daily Interference Scale, Pittsburgh Sleep Quality Index, the EuroQOL, Hospital Anxiety and Depression Scale and the Center for Epidemiologic Studies Depression Scale. RESULTS: Confirmatory factor analysis supported a two-factor model for hot flush symptoms (frequency and severity). Although there was strong convergence among self-reported hot flush measures, there was a high degree of unexplained variance associated with physiological measures. This suggests that self-report and physiological measures do not overlap substantially. The structural model showed that greater hot flush frequency and severity were directly related to greater perceived interference with daily life activities. Greater perceived interference, in turn, directly predicted greater sleep disruption, which predicted lower perceived health state and more symptoms of anxiety and depression. CONCLUSIONS: Findings suggest hot flush interference may be the most appropriate single measure to include in clinical trials of vasomotor symptom therapies. Measuring and ameliorating patients' perceptions of hot flush interference with life activities and subjective sleep quality may be the most direct routes to improving quality of life.


Assuntos
Neoplasias da Mama/psicologia , Análise Fatorial , Fogachos/psicologia , Modelos Biológicos , Qualidade de Vida , Ansiedade/psicologia , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Depressão/psicologia , Feminino , Resposta Galvânica da Pele , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Monitorização Ambulatorial , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/psicologia , Inquéritos e Questionários , Sobreviventes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA