RESUMO
Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
Assuntos
Microbiologia do Ar , Biodiversidade , DNA Fúngico , Fungos , Estações do Ano , Análise Espaço-Temporal , DNA Fúngico/análise , DNA Fúngico/genética , Fungos/genética , Fungos/classificação , Fungos/isolamento & purificação , Micorrizas/genética , Micorrizas/classificação , Micorrizas/isolamento & purificação , Filogenia , Esporos Fúngicos/classificação , Esporos Fúngicos/isolamento & purificação , Temperatura , Clima Tropical , Mapeamento GeográficoRESUMO
Although p53 inactivation promotes genomic instability1 and presents a route to malignancy for more than half of all human cancers2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases-Trp53 (encoding mouse p53) loss of heterozygosity, accumulation of deletions, genome doubling, and the emergence of gains and amplifications-each associated with specific histological stages across the premalignant and malignant spectrum. Despite rampant heterogeneity, the deletion events that follow p53 inactivation target functionally relevant pathways that can shape genomic evolution and remain fixed as homogenous events in diverse malignant populations. Thus, loss of p53-the 'guardian of the genome'-is not merely a gateway to genetic chaos but, rather, can enable deterministic patterns of genome evolution that may point to new strategies for the treatment of TP53-mutant tumours.
Assuntos
Carcinogênese , Progressão da Doença , Genes p53 , Genoma , Perda de Heterozigosidade , Neoplasias Pancreáticas , Proteína Supressora de Tumor p53 , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Evolução Molecular , Deleção de Genes , Genes p53/genética , Genoma/genética , Camundongos , Modelos Genéticos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Complex incubation strategies have evolved to solve the trade-off between parent survival and care for their eggs with often brief departures (recesses) that maximize egg survival, and infrequent extended recesses maximizing adult condition. Here we examined incubation behaviour of sanderlings (Calidris alba), a species that exhibits both biparental and uniparental incubation behaviour. During 11 breeding seasons in Greenland, we have quantified incubation variability with thermologgers placed in nests. We estimated the impact of environmental conditions and individual characteristics on the occurrence and the duration of recesses. We found that extended recesses are a unique feature of uniparentals, and their frequency and duration increased in colder temperatures. The relationship was mediated by body condition, with individuals in poor condition performing longer extended recesses in colder temperatures. This suggests that extended recesses may represent a shift towards self-maintenance at the expense of the egg care, allowing birds to continue incubating under unfavourable conditions. Our study illustrates how extended recesses may be a key breeding strategy to overcome high energetic costs associated with incubation. Quantifying such behavioural flexibility paves the way for tracking future behavioural responses of individuals in the face of changing environments.
Assuntos
Charadriiformes , Humanos , Animais , Temperatura , Aves/fisiologia , Temperatura Baixa , CruzamentoRESUMO
Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota. Within and among species, however, the degree to which alterations in phenology match climate variability differ substantially. To better understand factors driving these differences, we evaluated variation in timing of nesting of eight Arctic-breeding shorebird species at 18 sites over a 23-year period. We used the Normalized Difference Vegetation Index as a proxy to determine the start of spring (SOS) growing season and quantified relationships between SOS and nest initiation dates as a measure of phenological responsiveness. Among species, we tested four life history traits (migration distance, seasonal timing of breeding, female body mass, expected female reproductive effort) as species-level predictors of responsiveness. For one species (Semipalmated Sandpiper), we also evaluated whether responsiveness varied across sites. Although no species in our study completely tracked annual variation in SOS, phenological responses were strongest for Western Sandpipers, Pectoral Sandpipers, and Red Phalaropes. Migration distance was the strongest additional predictor of responsiveness, with longer-distance migrant species generally tracking variation in SOS more closely than species that migrate shorter distances. Semipalmated Sandpipers are a widely distributed species, but adjustments in timing of nesting relative to variability in SOS did not vary across sites, suggesting that different breeding populations of this species were equally responsive to climate cues despite differing migration strategies. Our results unexpectedly show that long-distance migrants are more sensitive to local environmental conditions, which may help them to adapt to ongoing changes in climate.
Assuntos
Migração Animal , Mudança Climática , Comportamento de Nidação , Estações do Ano , Animais , Regiões Árticas , Migração Animal/fisiologia , Feminino , Charadriiformes/fisiologia , ReproduçãoRESUMO
Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey. Using data from 19 sites spanning a wide temperature gradient from the Subarctic to the High Arctic, we investigated the effects of temperature on the phenology and biomass of arthropods available to shorebirds during their short breeding season at high latitudes. We hypothesized that prolonged exposure to warmer summer temperatures would generate earlier peaks in arthropod biomass, as well as higher peak and seasonal biomass. Across the temperature gradient encompassed by our study sites (>10°C in average summer temperatures), we found a 3-day shift in average peak date for every increment of 80 cumulative thawing degree-days. Interestingly, we found a linear relationship between temperature and arthropod biomass only below temperature thresholds. Higher temperatures were associated with higher peak and seasonal biomass below 106 and 177 cumulative thawing degree-days, respectively, between June 5 and July 15. Beyond these thresholds, no relationship was observed between temperature and arthropod biomass. Our results suggest that prolonged exposure to elevated temperatures can positively influence prey availability for some arctic birds. This positive effect could, in part, stem from changes in arthropod assemblages and may reduce the risk of trophic mismatch.
Assuntos
Artrópodes , Biomassa , Estações do Ano , Temperatura , Animais , Regiões Árticas , Artrópodes/fisiologia , Mudança Climática , Cadeia Alimentar , Charadriiformes/fisiologia , Migração AnimalRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, which limits surgical options and portends a dismal prognosis. Current oncologic PDAC therapies confer marginal benefit and, thus, a significant unmet clinical need exists for new therapeutic strategies. To identify effective PDAC therapies, we leveraged a syngeneic orthotopic PDAC transplant mouse model to perform a large-scale, in vivo screen of 16 single-agent and 41 two-drug targeted therapy combinations in mice. Among 57 drug conditions screened, combined inhibition of heat shock protein (Hsp)-90 and MEK was found to produce robust suppression of tumor growth, leading to an 80% increase in the survival of PDAC-bearing mice with no significant toxicity. Mechanistically, we observed that single-agent MEK inhibition led to compensatory activation of resistance pathways, including components of the PI3K/AKT/mTOR signaling axis, which was overcome with the addition of HSP90 inhibition. The combination of HSP90(i) + MEK(i) was also active in vitro in established human PDAC cell lines and in vivo in patient-derived organoid PDAC transplant models. These findings encourage the clinical development of HSP90(i) + MEK(i) combination therapy and highlight the power of clinically relevant in vivo model systems for identifying cancer therapies.
Assuntos
Antineoplásicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Animais , Antineoplásicos/uso terapêutico , Benzodioxóis/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Sinergismo Farmacológico , Expressão Gênica , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Terapia de Alvo Molecular , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/farmacologia , Purinas/farmacologia , Piridonas/farmacologia , Pirimidinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Taxa de Sobrevida , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013. Blood Hg concentrations, which reflect Hg exposure in the local area in individual shorebirds: 1) ranged from 0.01-3.52 µg/g ww, with an overall mean of 0.30 ± 0.27 µg/g ww; 2) were influenced by species and study site, but not sampling year, with birds sampled near Utqiagvik, AK, having the highest concentrations; and 3) were influenced by foraging habitat at some sites. Feather Hg concentrations, which reflected Hg exposure from the wintering grounds: 1) ranged from 0.07-12.14 µg/g fw in individuals, with an overall mean of 1.14 ± 1.18 µg/g fw; and 2) were influenced by species and year. Most Arctic-breeding shorebirds had blood and feather Hg concentrations at levels where no adverse effects of exposure were predicted, though some individuals sampled near Utqiagvik had Hg levels that would be considered of concern. Overall, these data increase our understanding of how Hg is distributed in the various shorebird breeding areas of the Arctic, what factors predispose Arctic-breeding shorebirds to Hg exposure, and lay the foundation for future monitoring efforts.
Assuntos
Monitoramento Ambiental , Mercúrio , Humanos , Animais , Ecossistema , Aves , Mercúrio/análise , CruzamentoRESUMO
Flying over the open sea is energetically costly for terrestrial birds. Despite this, over-water journeys of many birds, sometimes hundreds of kilometres long, are uncovered by bio-logging technology. To understand how these birds afford their flights over the open sea, we investigated the role of atmospheric conditions, specifically wind and uplift, in subsidizing over-water flight at a global scale. We first established that ΔT, the temperature difference between sea surface and air, is a meaningful proxy for uplift over water. Using this proxy, we showed that the spatio-temporal patterns of sea-crossing in terrestrial migratory birds are associated with favourable uplift conditions. We then analysed route selection over the open sea for five facultative soaring species, representative of all major migratory flyways. The birds maximized wind support when selecting their sea-crossing routes and selected greater uplift when suitable wind support was available. They also preferred routes with low long-term uncertainty in wind conditions. Our findings suggest that, in addition to wind, uplift may play a key role in the energy seascape for bird migration that in turn determines strategies and associated costs for birds crossing ecological barriers such as the open sea.
Assuntos
Voo Animal , Vento , Migração Animal , Animais , Aves , ÁguaRESUMO
Most small rodent populations in the world have fascinating population dynamics. In the northern hemisphere, voles and lemmings tend to show population cycles with regular fluctuations in numbers. In the southern hemisphere, small rodents tend to have large amplitude outbreaks with less regular intervals. In the light of vast research and debate over almost a century, we here discuss the driving forces of these different rodent population dynamics. We highlight ten questions directly related to the various characteristics of relevant populations and ecosystems that still need to be answered. This overview is not intended as a complete list of questions but rather focuses on the most important issues that are essential for understanding the generality of small rodent population dynamics.
Assuntos
Ecossistema , Roedores , Animais , Arvicolinae , Surtos de Doenças , Dinâmica PopulacionalRESUMO
Climatic impacts are especially pronounced in the Arctic, which as a region is warming twice as fast as the rest of the globe. Here, we investigate how mean climatic conditions and rates of climatic change impact parasitoid insect communities in 16 localities across the Arctic. We focus on parasitoids in a widespread habitat, Dryas heathlands, and describe parasitoid community composition in terms of larval host use (i.e., parasitoid use of herbivorous Lepidoptera vs. pollinating Diptera) and functional groups differing in their closeness of host associations (koinobionts vs. idiobionts). Of the latter, we expect idiobionts-as being less fine-tuned to host development-to be generally less tolerant to cold temperatures, since they are confined to attacking hosts pupating and overwintering in relatively exposed locations. To further test our findings, we assess whether similar climatic variables are associated with host abundances in a 22 year time series from Northeast Greenland. We find sites which have experienced a temperature rise in summer while retaining cold winters to be dominated by parasitoids of Lepidoptera, with the reverse being true for the parasitoids of Diptera. The rate of summer temperature rise is further associated with higher levels of herbivory, suggesting higher availability of lepidopteran hosts and changes in ecosystem functioning. We also detect a matching signal over time, as higher summer temperatures, coupled with cold early winter soils, are related to high herbivory by lepidopteran larvae, and to declines in the abundance of dipteran pollinators. Collectively, our results suggest that in parts of the warming Arctic, Dryas is being simultaneously exposed to increased herbivory and reduced pollination. Our findings point to potential drastic and rapid consequences of climate change on multitrophic-level community structure and on ecosystem functioning and highlight the value of collaborative, systematic sampling effort.
Assuntos
Ecossistema , Herbivoria , Animais , Regiões Árticas , Groenlândia , Interações Hospedeiro-Parasita , LarvaRESUMO
The poleward range shift of the red fox (Vulpes vulpes) > 1,700 km into the Arctic is one of the most remarkable distribution changes of the early twentieth century. While this expansion threatens a smaller arctic ecological equivalent, the arctic fox (Vulpes lagopus), the case became a textbook example of climate-driven range shifts. We tested this classical climate change hypothesis linked to an important range shift which has attracted little research thus far. We analysed Canadian fur harvest data from the Hudson's Bay Company Archives (14 trading posts; 1926-1950), testing hypotheses based on changes in summer and winter climates. Summer warming might have triggered a bottom-up increase in ecosystem productivity, while winter warming might have lowered thermal stress, both favouring red fox expansion. Additionally, we evaluated the hypothesis that red fox expansion was driven by the appearance of human sedentary sites (n = 110) likely bringing food subsidies into the unproductive tundra. Analysis of red fox expansion chronologies showed that expansion speed was higher during warmer winters. However, the expansions occurred under both cooling and warming trends, being faster during cooler summers in the Baffin Island region. The increasing proportion of red fox in fox fur harvests was best explained by human activity, while generalized linear mixed models also revealed a marginal effect of warmer winters. Generalized additive models confirmed human presence as the most important factor explaining rates of change in the proportion of red fox in fox fur harvests. Using historical ecology, we disentangled the relative influences of climate change and anthropogenic habitat change, two global drivers that transformed arctic biodiversity during the last century and will likely continue to do so during this century. Anthropogenic food subsidies, which constitute stable food sources, facilitated the invasion of the tundra biome by a new mammalian predator and competitor, with long-term consequences that still remain to be understood.
Assuntos
Ecossistema , Raposas , Animais , Regiões Árticas , Biodiversidade , Canadá , HumanosRESUMO
Climate change can impact ecosystems by reshaping the dynamics of resource exploitation for predators and their prey. Alterations of these pathways could be especially intense in ecosystems characterized by a simple trophic structure and rapid warming trends, such as in the Arctic. However, quantifying the multiple direct and indirect pathways through which climate change is likely to alter trophic interactions and their relative strength remains a challenge. Here, we aim to identify direct and indirect causal mechanisms driven by climate affecting predator-prey interactions of species sharing a tundra food web. We based our study on relationships between one Arctic predator (Arctic fox) and its two main prey - lemmings (preferred prey) and snow geese (alternate prey) - which are exposed to variable local and regional climatic factors across years. We used a combination of models mapping multiple causal links among key variables derived from a long-term dataset (21 years). We obtained several possible scenarios linking regional climate factors (Arctic oscillations) and local temperature and precipitation to the breeding of species. Our results suggest that both regional and local climate factors have direct and indirect impacts on the breeding of foxes and geese. Local climate showed a positive causal link with goose nesting success, while both regional and local climate displayed contrasted effects on the proportion of fox breeding. We found no impact of climate on lemming abundance. We observed positive relationships between lemming, fox and goose reproduction highlighting numerical and functional responses of fox to the variability of lemming abundance. Our study measures causal links and strength of interactions in a food web, quantifying both numerical response of a predator and apparent interactions between its two main prey. These results improve our understanding of the complex effects of climate on predator-prey interactions and our capacity to anticipate food web response to ongoing climate change.
Les changements climatiques peuvent avoir un impact sur les écosystèmes au travers des modifications de la dynamique d'exploitation des ressources par les prédateurs et leurs proies. Dans le cas de l'Arctique, caractérisée par un réseau trophique simple et une sensibilité marquée au réchauffement climatique, l'altération de ces relations trophiques pourrait être particulièrement importante. Cependant, la quantification des nombreux liens directs et indirects à travers lesquels les changements climatiques peuvent affecter les interactions trophiques demeure un défi. Notre objectif est d'identifier les mécanismes causaux directs et indirects, sous-tendus par le climat, affectant les interactions prédateur-proie au sein d'un réseau trophique au cÅur de la toundra. Notre étude se base sur les relations entre un prédateur (renard arctique) et ses deux proies principales -le lemming (proie préférée) et la grande oie des neiges (proie alternative)- et qui subissent un accroissement des précipitations et des températures au travers des années. Nous avons utilisé une combinaison de modèles illustrant les liens causaux multiples entre les variables clés issues d'une base de données à long-terme (21 ans). Nous avons obtenu plusieurs scénarios possibles reliant les facteurs climatiques régionaux (Oscillation Arctique) et les températures et précipitations locales à la reproduction de nos 3 espèces. Nos résultats suggèrent que les facteurs climatiques régionaux et locaux présentent des impacts directs et indirects sur la reproduction du renard arctique et de l'oie des neiges. Le climat local présente un lien causal positif avec le succès de nidification de l'oie, alors que le climat local et régional démontrent un effet contrasté sur la proportion de renard en reproduction. Aucune relation entre les facteurs climatiques et l'abondance des lemmings n'a été trouvée. Nous avons observé des liens causaux positifs entre la reproduction du lemming, du renard et de l'oie, mettant en évidence les réponses numériques et fonctionnelles du renard arctique face à la variabilité de l'abondance de lemming. Notre étude est une des premières à mesurer les liens causaux et les forces d'interaction entre les espèces partageant un même réseau trophique, quantifiant ainsi la réponse numérique du prédateur et les interactions apparentes entre ses proies principales. Ces résultats améliorent notre compréhension des effets complexes du climat sur les interactions prédateur-proie et notre capacité à anticiper la réponse des réseaux trophiques aux changements climatiques en cours.
Assuntos
Ecossistema , Tundra , Animais , Regiões Árticas , Arvicolinae , Cadeia Alimentar , Dinâmica PopulacionalRESUMO
Material and energy flows among ecosystems can directly and indirectly drive ecosystem functions. Yet, how populations of consumers respond to allochthonous inputs at a macroecological scale is still unclear. Using a meta-analysis spanning several biomes, we show that the abundance of recipient populations is 36-57% larger with increased allochthonous inputs. The strength of direct effects on the recipients of these inputs as well as the indirect effects on the consumers of these recipients (i.e. ascending indirect effects) are constant across a latitudinal gradient spanning subtropical, arid, temperate, boreal and arctic ecosystems. However, indirect effect on the in situ resources of the input recipient (i.e. descending indirect effects) decreases with latitude. Our results suggest that the influence of allochthonous inputs can vary across large-scale gradients of ecosystem productivity and may be driven by the types of trophic interactions within recipient food webs.
Assuntos
Ecossistema , Cadeia Alimentar , Animais , EcologiaRESUMO
RATIONALE: Stable isotope analysis is widely used to reconstruct diet, delineate trophic interactions, and determine energy pathways. Such ecological inferences are based on the idea that animals are, isotopically, what they eat but with a predictable difference between the isotopic ratio of a consumer and that of its diet, coined as the discrimination factor. Providing correct estimates of diet-consumer isotopic discrimination in controlled conditions is key for a robust application of the stable isotopes technique in the wild. METHODS: Using a Finnigan Mat Delta Plus isotope-ratio mass spectrometer, we investigated isotopic discrimination of carbon and nitrogen isotope ratios (δ13 C and δ15 N values) in guard hairs of four Arctic predators; the wolf (n = 7), the wolverine (n = 2), the grizzly bear (n = 2), and the polar bear (n = 3). During a 3-month trial, carnivores were fed a mixed diet. The δ13 C and δ15 N values, and the mass (g) of diet items, were monitored weekly for each individual to determine their Total Diet Average ratios. RESULTS: Diet-hair isotopic discrimination (Δx) varied according to species, ranging [1.88 ± 0.69: 3.2 ± 0.69] for δ13 C values, and [1.58 ± 0.17: 3.81 ± 0.22] for δ15 N values. Adult wolves Δ13 C average (2.03 ± 0.7) was lower than that of young wolves (2.60 ± 0.8) and any other species (combined average of 2.59 ± 0.28), except for the wolverine (2.12 ± 0.23). Wolves Δ15 N averages (juveniles: 3.51 ± 0.34, adults: 3.68 ± 0.28) were higher than those of any other species (combined average: 2.50 ± 0.58). CONCLUSIONS: The discrimination factors for δ13 C and δ15 N values calculated in this study could be used in ecological studies dealing with free-ranging animals, with implications for non-invasive research approaches. As in other controlled discrimination studies, we recommend caution in applying our discrimination factors when the population structure is heterogeneous.
Assuntos
Isótopos de Carbono/análise , Carnivoridade/fisiologia , Espécies em Perigo de Extinção , Cabelo/química , Isótopos de Nitrogênio/análise , Animais , Regiões Árticas , Feminino , Análise de Alimentos/métodos , Espectrometria de Massas/métodos , Ursidae/fisiologia , Lobos/fisiologiaRESUMO
Global warming threatens to reduce population connectivity for terrestrial wildlife through significant and rapid changes to sea ice. Using genetic fingerprinting, we contrasted extant connectivity in island-dwelling Peary caribou in northern Canada with continental-migratory caribou. We next examined if sea-ice contractions in the last decades modulated population connectivity and explored the possible impact of future climate change on long-term connectivity among island caribou. We found a strong correlation between genetic and geodesic distances for both continental and Peary caribou, even after accounting for the possible effect of sea surface. Sea ice has thus been an effective corridor for Peary caribou, promoting inter-island connectivity and population mixing. Using a time series of remote sensing sea-ice data, we show that landscape resistance in the Canadian Arctic Archipelago has increased by approximately 15% since 1979 and may further increase by 20-77% by 2086 under a high-emission scenario (RCP8.5). Under the persistent increase in greenhouse gas concentrations, reduced connectivity may isolate island-dwelling caribou with potentially significant consequences for population viability.
Assuntos
Camada de Gelo , Rena/genética , Alaska , Distribuição Animal , Animais , Regiões Árticas , Canadá , Mudança Climática , Ilhas , Repetições de Microssatélites , Dinâmica PopulacionalRESUMO
Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms.
Assuntos
Cromossomos de Mamíferos , DNA/análise , Fluxo Gênico , Ursidae/genética , Cromossomo Y , Animais , Evolução Molecular , Feminino , Especiação Genética , Variação Genética , Haplótipos , Masculino , Repetições de Microssatélites , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Fatores Sexuais , Irmãos , Ursidae/classificaçãoRESUMO
Migrastatin is a biologically active natural product isolated from Streptomyces that has been shown to inhibit tumor cell migration. Upon completion of the first total synthesis of migrastatin, a number of structurally simplified analogs were prepared. Following extensive in vitro screening, a new generation of analogs was identified that demonstrates substantially higher levels of in vitro inhibitory activity, stability and synthetic accessibility when compared to the parent natural product. Herein, we describe two promising ether-derivative analogs, the migrastatin core ether (ME) and the carboxymethyl-ME (CME), which exhibit high efficacy in blocking tumor cell migration and metastasis in lung cancer. These compounds show an in vitro migration inhibition in the micromolar range (IC(50): ME 1.5 to 8.2 µM, CME 0.5 to 5 µM). In a human small-cell lung carcinoma (SCLC) primary xenograft model, ME and CME compounds were found to be highly potent in inhibiting overall metastasis even at the lowest dosage used (degree of inhibition: 96.2% and 99.3%, respectively). Together these very encouraging findings suggest that these analogs have promise as potent antimetastatic agents in lung cancer.
Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Macrolídeos/síntese química , Macrolídeos/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Piperidonas/síntese química , Piperidonas/uso terapêutico , Animais , Linhagem Celular Tumoral , Movimento Celular , Éteres/síntese química , Éteres/química , Humanos , Macrolídeos/química , Masculino , Camundongos , Metástase Neoplásica/patologia , Piperidonas/química , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Predation is an important ecological process that can significantly impact the maintenance of ecosystem services. In arctic environments, the relative ecological importance of predation is thought to be increasing due to climate change, partly because of increased productivity with rising temperatures. Therefore, understanding predator-prey interactions in arctic ecosystems is vital for the sustainable management of these northern regions. Network theory provides a framework for quantifying the structures of ecological interactions. In this study, we use dietary observations on mammalian and avian predators in a high arctic region, including isolated peninsulas on Ellesmere Island and north Greenland, to construct bipartite trophic networks. We quantify the complexity, specialization, and nested as well as modular structures of these networks and also determine if these properties varied among the peninsulas. Mammal prey remains were the dominant diet item for all predators, but there was spatial variation in diet composition among peninsulas. The predator-prey networks were less complex, had more specialized interactions, and were more nested and more modular than random expectations. However, the networks displayed only moderate levels of modularity. Predator species had less specialized interactions with prey than prey had with predators. All network properties differed among the peninsulas, which highlights that ecosystems often show complex responses to environmental characteristics. We suggest that gaining knowledge about spatial variation in the characteristics of predator-prey interactions can enhance our ability to manage ecosystems exposed to environmental perturbations, particularly in high arctic environments subject to rapid environmental change.