Publications by authors named "Nicolas Lecomte"

51 Publications

The interplay of wind and uplift facilitates over-water flight in facultative soaring birds.

Proc Biol Sci 2021 09 8;288(1958):20211603. Epub 2021 Sep 8.

Department of Migration, Max Planck Institute of Animal Behavior, Germany.

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 Δ, 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.
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http://dx.doi.org/10.1098/rspb.2021.1603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424339PMC
September 2021

Ecology of Arctic rabies: 60 years of disease surveillance in the warming climate of northern Canada.

Zoonoses Public Health 2021 09 13;68(6):601-608. Epub 2021 May 13.

Groupe de Recherche en Épidémiologie des Zoonoses et Santé Publique, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada.

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.
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http://dx.doi.org/10.1111/zph.12848DOI Listing
September 2021

Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules.

Cancer Res 2021 04 25;81(8):2002-2014. Epub 2021 Feb 25.

Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York.

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.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137674PMC
April 2021

Size matters: When resource accessibility by ecosystem engineering elicits wood-boring beetle demographic responses.

Ecol Evol 2021 Jan 7;11(2):784-795. Epub 2020 Dec 7.

Département de biologie Université de Moncton Moncton NB Canada.

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 () 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.
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http://dx.doi.org/10.1002/ece3.7079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820143PMC
January 2021

Population cycles and outbreaks of small rodents: ten essential questions we still need to solve.

Oecologia 2021 Mar 28;195(3):601-622. Epub 2020 Dec 28.

Department of Biological and Environmental Science, Konnevesi Research Station, University of Jyväskylä, P.O. Box 35, 40014, Jyväskylä, Finland.

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.
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http://dx.doi.org/10.1007/s00442-020-04810-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940343PMC
March 2021

Unbiased in vivo preclinical evaluation of anticancer drugs identifies effective therapy for the treatment of pancreatic adenocarcinoma.

Proc Natl Acad Sci U S A 2020 12 16;117(48):30670-30678. Epub 2020 Nov 16.

David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065;

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.
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http://dx.doi.org/10.1073/pnas.1920240117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720119PMC
December 2020

Parasites of an Arctic scavenger; the wolverine ( ).

Int J Parasitol Parasites Wildl 2020 Dec 16;13:178-185. Epub 2020 Oct 16.

School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff University, Cardiff, Wales, UK.

Parasites are fundamental components within all ecosystems, shaping interaction webs, host population dynamics and behaviour. Despite this, baseline data is lacking to understand the parasite ecology of many Arctic species, including the wolverine ( ), a top Arctic predator and scavenger. Here, we combined traditional count methods (i.e. adult helminth recovery, where taxonomy was confirmed by molecular identification) with 18S rRNA high-throughput sequencing to document the wolverine parasite community. Further, we investigated whether the abundance of parasites detected using traditional methods were associated with host metadata, latitude, and longitude (ranging from the northern limit of the boreal forest to the low Arctic and Arctic tundra in Nunavut, Canada). Adult parasites in intestinal contents were identified as in 72% (n = 39) of wolverines and spp. in 22% (n = 12), of which specimens from 2 wolverines were identified as based on COX1 sequence. 18S rRNA high-throughput sequencing on DNA extracted from faeces detected additional parasites, including a pseudophyllid cestode ( spp. or spp.), two metastrongyloid lungworms ( spp. or spp., and spp.), an ascarid nematode ( spp. or spp.), a spp. nematode, and the protozoan spp., though each at a prevalence less than 13% (n = 7). The abundance of significantly decreased with latitude (slope = -0.68; R = 0.17; P = 0.004), suggesting a northerly limit in distribution. We describe and in Canadian wolverines for the first time since 1978, and extend the recorded geographic distribution of these parasites ca 2000 km to the East and into the tundra ecosystem. Our findings illustrate the value of molecular methods in support of traditional methods, encouraging additional work to improve the advancement of molecular screening for parasites.
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http://dx.doi.org/10.1016/j.ijppaw.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591336PMC
December 2020

Behavioural responses of breeding arctic sandpipers to ground-surface temperature and primary productivity.

Sci Total Environ 2021 Feb 24;755(Pt 2):142485. Epub 2020 Sep 24.

The University Centre in Svalbard, 9171 Longyearbyen, Norway; Norwegian Institute for Nature Research, 5006 Bergen, Norway; Department of Biological Sciences, University of Bergen, 5020 Bergen, Norway.

Most birds incubate their eggs, which requires time and energy at the expense of other activities. Birds generally have two incubation strategies: biparental where both mates cooperate in incubating eggs, and uniparental where a single parent incubates. In harsh and unpredictable environments, incubation is challenging due to high energetic demands and variable resource availability. We studied the relationships between the incubation behaviour of sandpipers (genus Calidris) and two environmental variables: temperature and a proxy of primary productivity (i.e. NDVI). We investigated how these relationships vary between incubation strategies and across species among strategies. We also studied how the relationship between current temperature and incubation behaviour varies with previous day's temperature. We monitored the incubation behaviour of nine sandpiper species using thermologgers at 15 arctic sites between 2016 and 2019. We also used thermologgers to record the ground surface temperature at conspecific nest sites and extracted NDVI values from a remote sensing product. We found no relationship between either environmental variables and biparental incubation behaviour. Conversely, as ground-surface temperature increased, uniparental species decreased total duration of recesses (TDR) and mean duration of recesses (MDR), but increased number of recesses (NR). Moreover, small species showed stronger relationships with ground-surface temperature than large species. When all uniparental species were combined, an increase in NDVI was correlated with higher mean duration, total duration and number of recesses, but relationships varied widely across species. Finally, some uniparental species showed a lag effect with a higher nest attentiveness after a warm day while more recesses occurred after a cold day than was predicted based on current temperatures. We demonstrate the complex interplay between shorebird incubation strategies, incubation behaviour, and environmental conditions. Understanding how species respond to changes in their environment during incubation helps predict their future reproductive success.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142485DOI Listing
February 2021

Parasitoids indicate major climate-induced shifts in arctic communities.

Glob Chang Biol 2020 Nov 11;26(11):6276-6295. Epub 2020 Sep 11.

Department of Integrative Biology, University of Guelph, Guelph, ON, Canada.

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.
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http://dx.doi.org/10.1111/gcb.15297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692897PMC
November 2020

Combining stable isotopes, morphological, and molecular analyses to reconstruct the diet of free-ranging consumers.

Ecol Evol 2020 Jul 27;10(13):6664-6676. Epub 2020 May 27.

Caribou Ungava Centre d'études nordiques Université Laval Québec QC Canada.

Accurate estimates of animal diet composition are essential to untangle complex interactions in food webs. Biomarkers and molecular tools are increasingly used to estimate diet, sometimes alongside traditional dietary tracing methods. Yet only a few empirical studies have compared the outcomes and potential gains of using a combination of these methods, especially using free-ranging animals with distinct foraging preferences.We used stable isotopes, morphological, and molecular analyses to investigate the diet of free-ranging consumers with two distinct diet types, that is, carnivore and omnivore. By combining the three analytical methods to assess the diet of consumers during the same period, we aimed to identify the limits of each method and to assess the potential benefits of their combined use to derive diet estimates.Our results showed that the different methods led to a consistent diet description for carnivores, which have a relatively simple diet mixture, but their outcomes somewhat differed for omnivore, which have a more complex diet. Still, the combined use of morphological and molecular analyses enhanced the diversity of food sources detected compared to the use of a single method independently of diet types. Precision of diet estimates derived from stable isotope analyses was improved by the addition of priors obtained from morphological and molecular diet analyses of the same population.Although we used free-ranging animals without a known diet, our empirical testing of three of the most widely used methods of diet determination highlights the limits of relying over a single approach, especially in systems with few or no a priori information about the foraging habits of consumers. The choice of an appropriate approach of diet description should be a key step when planning dietary studies of free-ranging populations. We recommend using more than one dietary determination methods especially for species with complex diet mixtures.
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http://dx.doi.org/10.1002/ece3.6397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381590PMC
July 2020

Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer.

Cancer Cell 2020 08 18;38(2):198-211.e8. Epub 2020 Jun 18.

The Kinghorn Cancer Centre, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW, Australia.

Pancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity. Mutant p53 increases expression of splicing regulator hnRNPK to promote inclusion of cytosine-rich exons within GTPase-activating proteins (GAPs), negative regulators of RAS family members. Mutant p53-enforced GAP isoforms lose cell membrane association, leading to heightened KRAS activity. Preventing cytosine-rich exon inclusion in mutant KRAS/p53 PDACs decreases tumor growth. Moreover, mutant p53 PDACs are sensitized to inhibition of splicing via spliceosome inhibitors. These data provide insight into co-enrichment of KRAS and p53 mutations and therapeutics targeting this mechanism in PDAC.
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http://dx.doi.org/10.1016/j.ccell.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028848PMC
August 2020

Genomic Methods Identify Homologous Recombination Deficiency in Pancreas Adenocarcinoma and Optimize Treatment Selection.

Clin Cancer Res 2020 07 22;26(13):3239-3247. Epub 2020 May 22.

Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response-targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome.

Experimental Design: We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing. Homologous recombination gene mutations (HRm) were evaluated: , and HRm status was grouped as: (i) germline versus somatic; (ii) core ( and versus non-core (other HRm); and (iii) monoallelic versus biallelic. Genomic instability was compared using large-scale state transition, signature 3, and tumor mutation burden.

Results: Among 262 patients, 50 (19%) had HRD (15% germline and 4% somatic). Both groups were analyzed together due to lack of difference in their genomic instability and outcome. Median [95% confidence interval (CI)] follow-up was 21.9 (1.4-57.0) months. Median OS and PFS were 15.5 (14.6-19) and 7 (6.1-8.1) months, respectively. Patients with HRD had improved PFS compared with no HRD when treated with first-line (1L) platinum [HR, 0.44 (95% CI: 0.29-0.67); < 0.01], but not with 1L-non-platinum. Multivariate analysis showed HRD patients had improved OS regardless of their first-line treatment, but most had platinum exposure during their course. Biallelic HRm (11%) and core HRm (12%) had higher genomic instability, which translated to improved PFS on first-line platinum (1L-platinum) versus 1L-non-platinum.

Conclusions: Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380542PMC
July 2020

Arctic avian predators synchronise their spring migration with the northern progression of snowmelt.

Sci Rep 2020 04 29;10(1):7220. Epub 2020 Apr 29.

Max Planck Institute of Animal Behavior, Department of Migration, Am Obstberg 1, Radolfzell, 78315, Germany.

Migratory species display a range of migration patterns between irruptive (facultative) to regular (obligate), as a response to different predictability of resources. In the Arctic, snow directly influences resource availability. The causes and consequences of different migration patterns of migratory species as a response to the snow conditions remains however unexplored. Birds migrating to the Arctic are expected to follow the spring snowmelt to optimise their arrival time and select for snow-free areas to maximise prey encounter en-route. Based on large-scale movement data, we compared the migration patterns of three top predator species of the tundra in relation to the spatio-temporal dynamics of snow cover. The snowy owl, an irruptive migrant, the rough-legged buzzard, with an intermediary migration pattern, and the peregrine falcon as a regular migrant, all followed, as expected, the spring snowmelt during their migrations. However, the owl stayed ahead, the buzzard stayed on, and the falcon stayed behind the spatio-temporal peak in snowmelt. Although none of the species avoided snow-covered areas, they presumably used snow presence as a cue to time their arrival at their breeding grounds. We show the importance of environmental cues for species with different migration patterns.
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http://dx.doi.org/10.1038/s41598-020-63312-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190624PMC
April 2020

Paradigms for Precision Medicine in Epichaperome Cancer Therapy.

Cancer Cell 2019 11 24;36(5):559-573.e7. Epub 2019 Oct 24.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Program in Molecular Pharmacology, Sloan Kettering Institute, New York, NY 10065, USA.

Alterations in protein-protein interaction networks are at the core of malignant transformation but have yet to be translated into appropriate diagnostic tools. We make use of the kinetic selectivity properties of an imaging probe to visualize and measure the epichaperome, a pathologic protein-protein interaction network. We are able to assay and image epichaperome networks in cancer and their engagement by inhibitor in patients' tumors at single-lesion resolution in real time, and demonstrate that quantitative evaluation at the level of individual tumors can be used to optimize dose and schedule selection. We thus provide preclinical and clinical evidence in the use of this theranostic platform for precision medicine targeting of the aberrant properties of protein networks.
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http://dx.doi.org/10.1016/j.ccell.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996250PMC
November 2019

Correction to: Documenting lemming population change in the Arctic: Can we detect trends?

Ambio 2020 03;49(3):801-804

A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 33 Leninskij prosp, Moscow, Russia, 119071.

In the original published article, some of the symbols in figure 1A were modified incorrectly during the typesetting and publication process. The correct version of the figure is provided in this correction.
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http://dx.doi.org/10.1007/s13280-019-01262-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989706PMC
March 2020

ID1 Mediates Escape from TGFβ Tumor Suppression in Pancreatic Cancer.

Cancer Discov 2020 01 3;10(1):142-157. Epub 2019 Oct 3.

Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.

TGFβ is an important tumor suppressor in pancreatic ductal adenocarcinoma (PDA), yet inactivation of TGFβ pathway components occurs in only half of PDA cases. TGFβ cooperates with oncogenic RAS signaling to trigger epithelial-to-mesenchymal transition (EMT) in premalignant pancreatic epithelial progenitors, which is coupled to apoptosis owing to an imbalance of SOX4 and KLF5 transcription factors. We report that PDAs that develop with the TGFβ pathway intact avert this apoptotic effect via ID1. family members are expressed in PDA progenitor cells and encode components of a set of core transcriptional regulators shared by PDAs. PDA progression selects against TGFβ-mediated repression of . The sustained expression of uncouples EMT from apoptosis in PDA progenitors. AKT signaling and mechanisms linked to low-frequency genetic events converge on to preserve its expression in PDA. Our results identify ID1 as a crucial node and potential therapeutic target in PDA. SIGNIFICANCE: Half of PDAs escape TGFβ-induced tumor suppression without inactivating the TGFβ pathway. We report that expression is selected for in PDAs and that ID1 uncouples TGFβ-induced EMT from apoptosis. ID1 thus emerges as a crucial regulatory node and a target of interest in PDA..
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http://dx.doi.org/10.1158/2159-8290.CD-19-0529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954299PMC
January 2020

Direct and indirect effects of regional and local climatic factors on trophic interactions in the Arctic tundra.

J Anim Ecol 2020 03 11;89(3):704-715. Epub 2019 Oct 11.

Canada Research Chair in Polar and Boreal Ecology, Université de Moncton, Moncton, NB, Canada.

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.
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http://dx.doi.org/10.1111/1365-2656.13104DOI Listing
March 2020

Disentangling the relative influences of global drivers of change in biodiversity: A study of the twentieth-century red fox expansion into the Canadian Arctic.

J Anim Ecol 2020 02 9;89(2):565-576. Epub 2019 Sep 9.

Chaire de recherche du Canada en biodiversité nordique and Centre d'Études Nordiques, Université du Québec à Rimouski, Rimouski, QC, Canada.

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.
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http://dx.doi.org/10.1111/1365-2656.13090DOI Listing
February 2020

Documenting lemming population change in the Arctic: Can we detect trends?

Ambio 2020 Mar 22;49(3):786-800. Epub 2019 Jul 22.

A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 33 Leninskij prosp, Moscow, Russia, 119071.

Lemmings are a key component of tundra food webs and changes in their dynamics can affect the whole ecosystem. We present a comprehensive overview of lemming monitoring and research activities, and assess recent trends in lemming abundance across the circumpolar Arctic. Since 2000, lemmings have been monitored at 49 sites of which 38 are still active. The sites were not evenly distributed with notably Russia and high Arctic Canada underrepresented. Abundance was monitored at all sites, but methods and levels of precision varied greatly. Other important attributes such as health, genetic diversity and potential drivers of population change, were often not monitored. There was no evidence that lemming populations were decreasing in general, although a negative trend was detected for low arctic populations sympatric with voles. To keep the pace of arctic change, we recommend maintaining long-term programmes while harmonizing methods, improving spatial coverage and integrating an ecosystem perspective.
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http://dx.doi.org/10.1007/s13280-019-01198-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989711PMC
March 2020

Comment on "Global pattern of nest predation is disrupted by climate change in shorebirds".

Science 2019 06;364(6445)

Aptdo. Correos 32, 5480 Candeleda, Spain.

Kubelka (Reports, 9 November 2018, p. 680) claim that climate change has disrupted patterns of nest predation in shorebirds. They report that predation rates have increased since the 1950s, especially in the Arctic. We describe methodological problems with their analyses and argue that there is no solid statistical support for their claims.
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http://dx.doi.org/10.1126/science.aaw8529DOI Listing
June 2019

The strength of ecological subsidies across ecosystems: a latitudinal gradient of direct and indirect impacts on food webs.

Ecol Lett 2019 Feb 12;22(2):265-274. Epub 2018 Dec 12.

Department of Biology, Université de Moncton, Moncton, New Brunswick, E1A 3E9, Canada.

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.
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http://dx.doi.org/10.1111/ele.13185DOI Listing
February 2019

Discrimination factors of carbon and nitrogen stable isotopes from diet to hair in captive large Arctic carnivores of conservation concern.

Rapid Commun Mass Spectrom 2018 Oct;32(20):1773-1780

Canada Research Chair on Northern Biodiversity and Centre for Northern Studies, Université du Québec à Rimouski, QC, Canada, G5L 3A1.

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 (δ C and δ 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 δ C and δ 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 δ C values, and [1.58 ± 0.17‰: 3.81 ± 0.22‰] for δ N values. Adult wolves Δ 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 Δ 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 δ C and δ 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.
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http://dx.doi.org/10.1002/rcm.8239DOI Listing
October 2018

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Cancer Discov 2018 09 31;8(9):1112-1129. Epub 2018 May 31.

Memorial Sloan Kettering Cancer Center, New York, New York.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. .
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http://dx.doi.org/10.1158/2159-8290.CD-18-0349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125219PMC
September 2018

Seasonal micro-migration in a farm-island population of striated caracaras () in the Falkland Islands.

Mov Ecol 2018 30;6. Epub 2018 Mar 30.

1Acopian Center for Conservation Learning, Hawk Mountain Sanctuary, 410 Summer Valley Road, Orwigsburg, PA 17961 USA.

Background: The extent to which seasonal changes in food availability affect small-scale movements in free-ranging populations of birds of prey is relatively little studied. Here we describe a seasonal "micro-migration" of a farm-island population of striated caracaras () in the Falkland Islands in response to seasonal changes in the availability of seabird carcasses. We banded more than 450 individuals on Saunders Island, deployed archival and satellite GPS data loggers on 17 individuals, and monitored movements within and between two feeding areas on Saunders Island, a "marine-subsidized" site near seabird colonies and an anthropogenic "human-subsidized" farm site 16 km to the southeast.

Results: During 67 observation days between 2010 and 2015, resightings of 312 banded caracaras were greater at the marine-subsidized site during austral summer than winter, and the total daily resightings varied significantly between spring versus summer, summer versus winter, autumn versus spring, and autumn versus winter. Resightings were higher at the human-subsidized site in austral winter than summer and the total daily resightings varied significantly across all bi-seasonal comparisons. Resightings indicated that at least 12 of 197 birds (6.1%) moved between the human- and marine-subsidized sites at least once during the same winter, 15 of 335 birds (4.5%) did so in spring, none of 164 birds did so in summer, and 16 of 297 birds (5.4%) did so in autumn. Individuals fitted with archival GPS data loggers at the marine-subsidized site in summer maintained highly localized 95% kernel core areas (0.55 ± 0.12 km [mean ± SD]), whereas those at the human-subsidized site in winter maintained larger 95% kernel core areas (3.8 ± 4.6 km). Two of 6 satellite-tagged individuals that summered at known caracara breeding colonies 80 km WNW of Saunders Island were subsequently resighted in winter at the human-subsidized site.

Conclusion: Our results suggest that seasonal shifts in food resource availability drive seasonal micro-migrations in a farm-island population of striated caracaras, and that farm sites can be critical in providing nutritional resources for caracaras when naturally occurring marine-subsidized resources become less available. Our results have important implications for striated caracara spatial ecology and conservation, as increased winter survival could improve the status of this globally Near-Threatened population.
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http://dx.doi.org/10.1186/s40462-018-0122-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878424PMC
March 2018

Unexpected diversity in socially synchronized rhythms of shorebirds.

Nature 2016 12 23;540(7631):109-113. Epub 2016 Nov 23.

Conservation Ecology Group, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Nijenborgh 7, Groningen 9747 AG, The Netherlands.

The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators. Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring). The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood. Here we investigate these rhythms in the context of biparental care, a particularly sensitive phase of social synchronization where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within- and between-species diversity in incubation rhythms. Between species, the median length of one parent's incubation bout varied from 1-19 h, whereas period length-the time in which a parent's probability to incubate cycles once between its highest and lowest value-varied from 6-43 h. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or who actively protect their nest against predators. Rhythms entrainable to the 24-h light-dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity. The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.
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http://dx.doi.org/10.1038/nature20563DOI Listing
December 2016

Loss of connectivity among island-dwelling Peary caribou following sea ice decline.

Biol Lett 2016 09;12(9)

LECA - Laboratoire d'Écologie Alpine - UMR CNRS 5553, Université Savoie Mont Blanc, 73376 Le Bourget-du-Lac, France

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046914PMC
http://dx.doi.org/10.1098/rsbl.2016.0235DOI Listing
September 2016

Is it safe to nest near conspicuous neighbours? Spatial patterns in predation risk associated with the density of American Golden-Plover nests.

PeerJ 2016 10;4:e2193. Epub 2016 Aug 10.

Canada Research Chair in Polar and Boreal Ecology, Université de Moncton, Moncton, NB, Canada; Centre d'Études Nordiques, Université du Québec à Rimouski, Rimouski, QC, Canada; Quebec Center for Biodiversity Science, Université du Québec à Rimouski, Rimouski, QC, Canada.

Predation is one of the main factors explaining nesting mortality in most bird species. Birds can avoid nest predation or reduce predation pressure by breeding at higher latitude, showing anti-predator behaviour, selecting nest sites protected from predators, and nesting in association with protective species. American Golden-Plovers (Pluvialis dominica) defend their territory by using various warning and distraction behaviours displayed at varying levels of intensity (hereafter "conspicuous behaviour"), as well as more aggressive behaviours such as aerial attacks, but only in some populations. Such antipredator behaviour has the potential to repel predators and thus benefit the neighbouring nests by decreasing their predation risk. Yet, conspicuous behaviour could also attract predators by signalling the presence of a nest. To test for the existence of a protective effect associated with the conspicuous antipredator behaviour of American Golden-Plovers, we studied the influence of proximity to plover nests on predation risk of artificial nests on Igloolik Island (Nunavut, Canada) in July 2014. We predicted that the predation risk of artificial nests would decrease with proximity to and density of plover nests. We monitored 18 plover nests and set 35 artificial nests at 30, 50, 100, 200, and 500 m from seven of those plover nests. We found that the predation risk of artificial nests increases with the density of active plover nests. We also found a significant negative effect of the distance to the nearest active protector nest on predation risk of artificial nests. Understanding how the composition and structure of shorebird communities generate spatial patterns in predation risks represents a key step to better understand the importance of these species of conservation concern in tundra food webs.
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http://dx.doi.org/10.7717/peerj.2193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991854PMC
September 2016

Sexing a sex-role-reversed species based on plumage: potential challenges in the red phalarope.

PeerJ 2016 2;4:e1989. Epub 2016 May 2.

Canada Research Chair in Polar and Boreal Ecology, Université de Moncton, Moncton, Canada; Centre d'Études Nordiques, Université du Québec à Rimouski, Rimouski, Canada; Département de Biologie, Université de Moncton, Moncton, Canada; Québec Center for Biodiversity Science, Université du Québec à Rimouski, Rimouski, Canada.

Sex-role reversal, in which males care for offspring, can occur when mate competition is stronger between females than males. Secondary sex traits and mate attracting displays in sex-role-reversed species are usually more pronounced in females than in males. The red phalarope (Phalaropus fulicarius) is a textbook example of a sex-role-reversed species. It is generally agreed that males are responsible for all incubation and parental care duties, whereas females typically desert males after having completed a clutch and may pair with new males to lay additional clutches. The breeding plumage of female red phalaropes is usually more brightly colored than male plumage, a reversed sexual dichromatism usually associated with sex-role reversal. Here, we confirm with PCR-based sexing that male red phalaropes can exhibit both the red body plumage typical of a female and the incubation behavior typical of a male. Our result, combined with previous observations of brightly colored red phalaropes incubating nests at the same arctic location (Igloolik Island, Nunavut, Canada), suggests that plumage dichromatism alone may not be sufficient to distinguish males from females in this breeding population of red phalaropes. This stresses the need for more systematic genetic sexing combined with standardized description of intersexual differences in red phalarope plumages. Determining whether such female-like plumage on males is a result of phenotypic plasticity or genetic variation could contribute to further understanding sex-role reversal strategies in the short Arctic summer.
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http://dx.doi.org/10.7717/peerj.1989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860308PMC
May 2016
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