Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
Mais filtros













Base de dados
Intervalo de ano de publicação
1.
Ecol Evol ; 14(6): e11470, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38826159

RESUMO

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.

2.
Glob Chang Biol ; 30(6): e17356, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38853470

RESUMO

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 Animal
3.
Sci Data ; 11(1): 561, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816458

RESUMO

Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.


Assuntos
Microbiologia do Ar , DNA Fúngico , Esporos Fúngicos , DNA Fúngico/análise , Fungos/genética , Fungos/classificação , Biodiversidade
4.
Glob Chang Biol ; 30(5): e17335, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38771086

RESUMO

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 , Reprodução
5.
Proc Biol Sci ; 291(2017): 20232264, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38378147

RESUMO

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 , Cruzamento
6.
Ecotoxicology ; 32(8): 1062-1083, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37874523

RESUMO

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 , Cruzamento
7.
Nature ; 620(7974): 499-500, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37587294

Assuntos
Ecossistema
8.
Ecology ; 104(6): e4047, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37261395

RESUMO

Tracking biodiversity shifts is central to understanding past, present, and future global changes. Recent advances in bioacoustics and the low cost of high-quality automatic recorders are revolutionizing studies in biogeography and community and behavioral ecology with a robust assessment of phenology, species occurrence, and individual activity. This large volume of acoustic recordings has recently generated a plethora of datasets that can now be handled automatically, mostly via big data methods such as deep learning. These approaches need high-quality annotations to classify and detect recorded sounds efficiently. However, very few strongly annotated datasets-that is, with detailed information on start and end time of each vocalization-are openly accessible to the public. Moreover, these datasets mostly cover temperate species and are usually limited to a single year of recordings. Here, we present ArcticBirdSounds, the first open-access, multisite, and multiyear strongly annotated dataset of arctic bird vocalizations. ArcticBirdSounds offers 20 h of annotated recordings over 2 years (2018, 2019), taken from 15 distinct plots within six locations across the Arctic, from Alaska to Greenland. Recordings cover the arctic vertebrates' breeding period and are evenly spaced during the day; they capture most species breeding there with 12,933 temporal annotations in 49 classes of sounds. While these data can be used for many pressing ecological questions, it is also a unique resource for methodological development to help meet the challenges of fast ecosystem transformations such as those happening in the Arctic. All data, including audio files, annotation files, and companion spreadsheets, are available in an Open Science Framework repository published under a CC BY 4.0 License.


Assuntos
Aves , Ecossistema , Animais , Regiões Árticas , Alaska , Biodiversidade
9.
Commun Biol ; 6(1): 153, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36746982

RESUMO

Population-genomic studies can shed new light on the effect of past demographic processes on contemporary population structure. We reassessed phylogeographical patterns of a classic model species of postglacial recolonisation, the brown bear (Ursus arctos), using a range-wide resequencing dataset of 128 nuclear genomes. In sharp contrast to the erratic geographical distribution of mtDNA and Y-chromosomal haplotypes, autosomal and X-chromosomal multi-locus datasets indicate that brown bear population structure is largely explained by recent population connectivity. Multispecies coalescent based analyses reveal cases where mtDNA haplotype sharing between distant populations, such as between Iberian and southern Scandinavian bears, likely results from incomplete lineage sorting, not from ancestral population structure (i.e., postglacial recolonisation). However, we also argue, using forward-in-time simulations, that gene flow and recombination can rapidly erase genomic evidence of former population structure (such as an ancestral population in Beringia), while this signal is retained by Y-chromosomal and mtDNA, albeit likely distorted. We further suggest that if gene flow is male-mediated, the information loss proceeds faster in autosomes than in X chromosomes. Our findings emphasise that contemporary autosomal genetic structure may reflect recent population dynamics rather than postglacial recolonisation routes, which could contribute to mtDNA and Y-chromosomal discordances.


Assuntos
Ursidae , Animais , Masculino , Ursidae/genética , DNA Mitocondrial/genética , Filogeografia , Dinâmica Populacional , Mitocôndrias/genética
10.
Nat Commun ; 13(1): 6513, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316305

RESUMO

Tumors initiate by mutations in cancer cells, and progress through interactions of the cancer cells with non-malignant cells of the tumor microenvironment. Major players in the tumor microenvironment are cancer-associated fibroblasts (CAFs), which support tumor malignancy, and comprise up to 90% of the tumor mass in pancreatic cancer. CAFs are transcriptionally rewired by cancer cells. Whether this rewiring is differentially affected by different mutations in cancer cells is largely unknown. Here we address this question by dissecting the stromal landscape of BRCA-mutated and BRCA Wild-type pancreatic ductal adenocarcinoma. We comprehensively analyze pancreatic cancer samples from 42 patients, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA Wild-type tumors. In particular, we detect an increase in a subset of immune-regulatory clusterin-positive CAFs in BRCA-mutated tumors. Using cancer organoids and mouse models we show that this process is mediated through activation of heat-shock factor 1, the transcriptional regulator of clusterin. Our findings unravel a dimension of stromal heterogeneity influenced by germline mutations in cancer cells, with direct implications for clinical research.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Clusterina , Fatores de Transcrição de Choque Térmico , Neoplasias Pancreáticas , Animais , Camundongos , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/patologia , Clusterina/genética , Clusterina/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Neoplasias Pancreáticas/patologia , Microambiente Tumoral/genética , Humanos , Neoplasias Pancreáticas
11.
Nature ; 608(7924): 795-802, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35978189

RESUMO

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/genética
12.
Cancer Res ; 82(19): 3549-3560, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35952360

RESUMO

Intratumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including pancreatic ductal adenocarcinoma (PDAC). As PDAC portends a dire prognosis, a better understanding of the mechanisms underpinning cellular diversity in PDAC is crucial. Here, we investigated the cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. Heterogeneity contracted significantly in two-dimensional and three-dimensional cell culture models but was restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquired cell states identified in autochthonous PDAC tumors, including a basal state exhibiting coexpression and coaccessibility of epithelial and mesenchymal genes. Lineage tracing combined with single-cell transcriptomics revealed that basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intratumoral heterogeneity in PDAC. SIGNIFICANCE: This work provides important insights into how different model systems of pancreatic ductal adenocarcinoma mold the phenotypic space of cancer cells, highlighting the power of in vivo models.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Humanos , Ductos Pancreáticos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Plásticos , Neoplasias Pancreáticas
14.
Eur J Psychotraumatol ; 13(1): 2055296, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479301

RESUMO

Background: Executive functioning has been linked to both the development of post-traumatic symptoms and the efficiency of therapy. Specifically, flexibility processes seem to play a major role in the use of efficient coping strategies after a traumatic event. However, only a few studies have focused on the links between flexibility, resilience, and concrete behaviours displayed by individuals. Objective: The aim of this study was to investigate the influence of emotional content on the efficiency of cognitive flexibility among trauma-exposed individuals. Method: Twenty-eight trauma-exposed (TE) and 27 non-trauma-exposed (NTE) individuals performed an overlap task in which neutral, positive, and negative pictures appeared in the centre of the screen. Participants were required to disengage their attentional focus from this picture to identify a peripheral target. Analyses included eye movements during the presentation of the scenes and the response times associated with target localization. Results: TE individuals initially presented a rapid overt disengagement from both neutral and negative emotional information. In other words, TE participants moved their gaze away from the central picture towards the target more rapidly than NTE participants. However, TE participants then displayed longer reaction times to identify the target in comparison with NTE participants. Discussion: This study presents preliminary evidence that cognitive flexibility may be relevant when considering the impact of trauma. The developed task could provide a novel way to assess this flexibility within an emotional context. HIGHLIGHTS: • This study developed an original assessment of cognitive flexibility processes in an emotional context.• Cognitive flexibility was assessed using an overlap task and eye-tracking technology.• Cognitive flexibility may be relevant when considering the impact of a trauma.


Antecedentes: El funcionamiento ejecutivo se ha relacionado tanto con el desarrollo de síntomas postraumáticos como con la eficiencia de la terapia. Específicamente, los procesos de flexibilidad parecen jugar un papel importante en el uso de estrategias de afrontamiento después de un evento traumático. Sin embargo, solo unos pocos estudios se han centrado en los vínculos entre la flexibilidad, la resiliencia y los comportamientos concretos que muestran los individuos.Objetivo: El objetivo de este estudio fue investigar la influencia del contenido emocional en la eficiencia de la flexibilidad cognitiva entre individuos expuestos a traumas.Método: 28 personas expuestas a trauma (ET) y 27 no expuestas a trauma (NET) realizaron una tarea superpuesta en la que aparecían imágenes neutras, positivas y negativas en el centro de la pantalla. Se pidió a los participantes que desvincularan su foco de atención de esta imagen para identificar un objetivo periférico. Los análisis incluyeron movimientos oculares durante la presentación de las escenas y los tiempos de respuesta asociados con la localización del objetivo.Resultados: Los individuos con ET inicialmente presentaron una desconexión abierta y rápida de la información emocional tanto neutral como negativa. En otras palabras, los participantes con ET alejaron su mirada de la imagen central hacia el objetivo más rápido que los participantes NET. Sin embargo, los participantes con ET mostraron tiempos de reacción más largos para identificar el objetivo en comparación con los participantes NET.Discusión: Los individuos con ET inicialmente presentaron una desconexión abierta y rápida de la información emocional tanto neutral como negativa. En otras palabras, los participantes con ET alejaron su mirada de la imagen central hacia el objetivo más rápido que los participantes NET. Sin embargo, los participantes con ET mostraron tiempos de reacción más largos para identificar el objetivo en comparación con los participantes NET.


Assuntos
Atenção , Tecnologia de Rastreamento Ocular , Atenção/fisiologia , Cognição , Humanos , Tempo de Reação/fisiologia , Sobreviventes
15.
Proc Biol Sci ; 288(1958): 20211603, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493076

RESUMO

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 , Água
16.
Zoonoses Public Health ; 68(6): 601-608, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33987941

RESUMO

Rabies occurs throughout the Arctic, representing an ongoing public health concern for residents of northern communities. The Arctic fox (Vulpes lagopus) is the main reservoir of the Arctic rabies virus variant, yet little is known about the epidemiology of Arctic rabies, such as the ecological mechanisms driving where and when epizootics in fox populations occur. In this study, we provide the first portrait of the spatio-temporal spread of rabies across northern Canada. We also explore the impact of seasonal and multiannual dynamics in Arctic fox populations and climatic factors on rabies transmission dynamics. We analysed data on rabies cases collected through passive surveillance systems in the Yukon, Northwest Territories, Nunavut, Nunavik and Labrador from 1953 to 2014. In addition, we analysed a large and unique database of trapped foxes tested for rabies in the Northwest Territories and Nunavut from 1974 to 1984 as part of active surveillance studies. Rabies cases occurred in all Arctic regions of Canada and were relatively synchronous among foxes and dogs (Canis familiaris). This study highlights the spread of Arctic rabies virus variant across northern Canada, with contrasting rabies dynamics between different yet connected areas. Population fluctuations of Arctic fox populations could drive rabies transmission dynamics in a complex way across northern Canada. Furthermore, this study suggests different impacts of climate and sea ice cover on the onset of rabies epizootics in northern Canada. These results lay the groundwork for the development of epidemiological models to better predict the spatio-temporal dynamics of rabies occurrence in both wild and domestic carnivores, leading to better estimates of human exposure and transmission risk.


Assuntos
Mudança Climática , Ecossistema , Raposas , Raiva/veterinária , Animais , Regiões Árticas/epidemiologia , Canadá/epidemiologia , Humanos , Vigilância da População , Raiva/epidemiologia
17.
Cancer Res ; 81(8): 2002-2014, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33632898

RESUMO

Pancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured 5' untranslated regions, including those with multiple G-quadruplex elements. Computational analyses identified these features in mRNAs encoding KRAS and key downstream molecules. Transcriptome-scale ribosome footprinting accurately identified eIF4A-dependent mRNAs in PDAC, including critical KRAS signaling molecules such as PI3K, RALA, RAC2, MET, MYC, and YAP1. These findings contrast with a recent study that relied on an older method, polysome fractionation, and implicated redox-related genes as eIF4A clients. Together, our findings highlight the power of ribosome footprinting in conjunction with deep RNA sequencing in accurately decoding translational control mechanisms and define the therapeutic mechanism of eIF4A inhibitors in PDAC. SIGNIFICANCE: These findings document the coordinate, eIF4A-dependent translation of RAS-related oncogenic signaling molecules and demonstrate therapeutic efficacy of eIF4A blockade in pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Fator de Iniciação 4A em Eucariotos/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Mensageiro/metabolismo , Ribossomos/metabolismo , Regiões 5' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cicloeximida/farmacologia , Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores , Quadruplex G , Genes ras/genética , Humanos , Camundongos , Camundongos Nus , Mutação , Transplante de Neoplasias , Oxirredução , Neoplasias Pancreáticas/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Polirribossomos/metabolismo , Biossíntese de Proteínas , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Helicases , Análise de Sequência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma , Triterpenos/farmacologia , Proteínas de Sinalização YAP , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas ral de Ligação ao GTP/genética , Proteínas ral de Ligação ao GTP/metabolismo , Proteína RAC2 de Ligação ao GTP
18.
Ecol Evol ; 11(2): 784-795, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33520166

RESUMO

Episodic natural disturbances play a key role in ecosystem renewal, and ecological engineering could do so by transforming resource accessibility. While such coupling creates nontrophic and lasting interactions between resource consumers and ecosystem engineers, it is unclear how large the disturbance must be to sustain such coupling. Natural disturbances that occur from the ecological engineering by the Canadian beaver (Castor canadensis) modulate deadwood dynamics in many forest ecosystems. Relying on such episodes of fresh woody debris, primary wood-boring beetles, organisms that dig tunnels into those debris for reproduction, act as important deadwood decomposers in the ecosystem. Here, we investigate how the age and size of beaver disturbances act as predictors for primary wood-boring beetle abundance and species richness around beaver-altered habitat patches. To do so, we sampled beetles around 16 beaver-disturbed and unaltered watercourses within the Kouchibouguac National Park (Canada) and modeled beetle demographic responses to site conditions and their physical characteristics, distance from the watercourse, deadwood biomass, and the geographical location of the sites. Our results indicate that the size of the disturbance is positively associated with beetle abundance, which highlights unique deadwood dynamics inherent to large beaver ponds. The role of beavers in forest ecosystems by reaching multiple taxa at multiple spatiotemporal scales further exemplifies the need to study nontrophic interactions and their complex consequences in ecosystem management.

20.
Oecologia ; 195(3): 601-622, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33369695

RESUMO

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 Populacional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA