Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Glob Chang Biol ; 30(4): e17271, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38613240

RESUMO

Ecological and evolutionary theories have proposed that species traits should be important in mediating species responses to contemporary climate change; yet, empirical evidence has so far provided mixed evidence for the role of behavioral, life history, or ecological characteristics in facilitating or hindering species range shifts. As such, the utility of trait-based approaches to predict species redistribution under climate change has been called into question. We develop the perspective, supported by evidence, that trait variation, if used carefully can have high potential utility, but that past analyses have in many cases failed to identify an explanatory value for traits by not fully embracing the complexity of species range shifts. First, we discuss the relevant theory linking species traits to range shift processes at the leading (expansion) and trailing (contraction) edges of species distributions and highlight the need to clarify the mechanistic basis of trait-based approaches. Second, we provide a brief overview of range shift-trait studies and identify new opportunities for trait integration that consider range-specific processes and intraspecific variability. Third, we explore the circumstances under which environmental and biotic context dependencies are likely to affect our ability to identify the contribution of species traits to range shift processes. Finally, we propose that revealing the role of traits in shaping species redistribution may likely require accounting for methodological variation arising from the range shift estimation process as well as addressing existing functional, geographical, and phylogenetic biases. We provide a series of considerations for more effectively integrating traits as well as extrinsic and methodological factors into species redistribution research. Together, these analytical approaches promise stronger mechanistic and predictive understanding that can help society mitigate and adapt to the effects of climate change on biodiversity.


Assuntos
Biodiversidade , Mudança Climática , Filogenia , Geografia , Fenótipo
2.
J Exp Zool A Ecol Integr Physiol ; 339(10): 1102-1115, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37723946

RESUMO

The colonization of novel environments requires a favorable response to conditions never, or rarely, encountered in recent evolutionary history. For example, populations colonizing upslope habitats must cope with lower atmospheric pressure at elevation, and thus reduced oxygen availability. The embryo stage in oviparous organisms is particularly susceptible, given its lack of mobility and limited gas exchange via diffusion through the eggshell and membranes. Especially little is known about responses of Lepidosaurian reptiles to reduced oxygen availability. To test the role of physiological plasticity during early development in response to high elevation hypoxia, we performed a transplant experiment with the viperine snake (Natrix maura, Linnaeus 1758). We maintained gravid females originating from low elevation populations (432 m above sea level [ASL]-normoxia) at both the elevation of origin and high elevation (2877 m ASL-extreme high elevation hypoxia; approximately 72% oxygen availability relative to sea level), then incubated egg clutches at both low and high elevation. Regardless of maternal exposure to hypoxia during gestation, embryos incubated at extreme high elevation exhibited altered developmental trajectories of cardiovascular function and metabolism across the incubation period, including a reduction in late-development egg mass. This physiological response may have contributed to the maintenance of similar incubation duration, hatching success, and hatchling body size compared to embryos incubated at low elevation. Nevertheless, after being maintained in hypoxia, juveniles exhibit reduced carbon dioxide production relative to oxygen consumption, suggesting altered energy pathways compared to juveniles maintained in normoxia. These findings highlight the role of physiological plasticity in maintaining rates of survival and fitness-relevant phenotypes in novel environments.


Assuntos
Colubridae , Feminino , Animais , Hipóxia/metabolismo , Oxigênio/metabolismo , Consumo de Oxigênio , Fenômenos Fisiológicos Cardiovasculares
3.
J Therm Biol ; 103: 103166, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35027206

RESUMO

Global warming impacts biodiversity worldwide, leading to species' adaptation, migration, or extinction. The population's persistence depends on the maintenance of essential activities, which is notably driven by phenotypic adaptation to local environments. Metabolic rate - that increases with temperature in ectotherms - is a key physiological proxy for the energy available to fuel individuals' activities. Cold-adapted ectotherms can exhibit a higher resting metabolism than warm-adapted ones to maintain functionality at higher elevations or latitudes, known as the metabolic cold-adaptation hypothesis. How climate change will affect metabolism in species inhabiting contrasting climates (cold or warm) is still a debate. Therefore, it is of high interest to assess the pace of metabolic responses to global warming among populations adapted to highly different baseline climatic conditions. Here, we conducted a physiological experiment in the endemic Pyrenean brook newt (Calotriton asper). We measured a proxy of standard metabolic rate (SMR) along a temperature gradient in individuals sampled among 6 populations located from 550 to 2189 m a.s.l. We demonstrated that SMR increased with temperature, but significantly diverged depending on populations' origins. The baseline and the slope of the relationship between SMR and temperature were both higher for high-elevation populations than for low-elevation populations. We discussed the stronger metabolic response observed in high-elevation populations suggesting a drop of performance in essential life activities for these individuals under current climate change. With the increase of metabolism as the climate warms, the metabolic-cold adaptation strategy selected in the past could compromise the sustainability of cold-adapted populations if short-term evolutionary responses do not allow to offset this evolutionary legacy.


Assuntos
Altitude , Regulação da Temperatura Corporal , Salamandridae/fisiologia , Aclimatação , Animais , Temperatura Corporal , Feminino , Aquecimento Global , Masculino , Oxigênio/metabolismo , Salamandridae/metabolismo
4.
JMIR Res Protoc ; 10(5): e21306, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33944792

RESUMO

BACKGROUND: Perceptual congruence has been defined as the level of agreement between partners on various aspects of their shared lives, including perceived engagement in individual and jointly performed activities. While the level of adjustment made by partners to such activities is thought to contribute to a couple's sense of mutuality, perceptions of time use concerning activity engagement has yet to be considered. As such, this study will determine the level of perceptual congruence between partners with respect to perceived time use in their respective and shared activities. OBJECTIVE: The primary objective of the IP-COUPLES study is to determine the similarities and differences between partners in terms of their perceptual congruence with respect to independent and jointly performed activities. This study will also examine the association between independent and joint activities in terms of perceptual congruence of time use and the strength of this association. METHODS: This descriptive observational study includes 100 couples from Western Switzerland who are recruited using snowball sampling methods. The Life Balance Inventory (LBI), a self-report questionnaire that captures activity configuration congruence, will measure independent and joint perceptions of both time use allocated to daily activities and corresponding satisfaction. Due to COVID-19, the protocol can be administered virtually by the primary investigator. The mean scores of perceptual congruence variables will be used for analysis, namely perceived congruence of time use in terms of independent and jointly performed activities. For the first objective, an independent t test will be used for each variable to compare the mean score between activities on the LBI. For the second objective, the correlations between the mean scores for these activities will be calculated for each variable using the Pearson correlation. RESULTS: The IP-COUPLES study protocol was developed in 2019 and 2020. Enrollment began in June 2020. Data collection will continue until October 2021 to account for time needed for recruitment due to the COVID-19 pandemic crisis. Analysis and presentation of results are expected in 2022. CONCLUSIONS: This study is exploratory, as it is the first to our knowledge to investigate how perceived time-use patterns with respect to independent or jointly performed activities are similar or different among romantic couples. By investigating the interpersonal perception of time-use patterns among couples, the IP-COUPLES study is an important first step to understanding how romantic partners' daily activities are contributing to the level of satisfaction as a partner and as a couple and to the sense of mutuality between partners in a romantic relationship. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21306.

5.
Nat Commun ; 12(1): 2574, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976140

RESUMO

Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.


Assuntos
Asma/terapia , Interleucina-13/antagonistas & inibidores , Interleucina-4/antagonistas & inibidores , Vacinação/métodos , Animais , Asma/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/imunologia , Doença Crônica/terapia , Modelos Animais de Doenças , Feminino , Humanos , Injeções Intramusculares , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Camundongos , Camundongos Transgênicos , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
6.
Science ; 370(6520)2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33243858

RESUMO

Zellweger et al (Reports, 15 May 2020, p. 772) claimed that forest plant communities' response to global warming is primarily controlled by microclimate dynamics. We show that community thermophilization is poorly explained by the underlying components of microclimate, and that global warming primarily controls the climatic lag of plant communities. Deconstructing the underlying components of microclimate provides insights for managers.


Assuntos
Florestas , Microclima , Aquecimento Global , Plantas
7.
Integr Zool ; 15(6): 544-557, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32649806

RESUMO

Climate change is generating range shifts in many organisms, notably along the elevational gradient in mountainous environments. However, moving up in elevation exposes organisms to lower oxygen availability, which may reduce the successful reproduction and development of oviparous organisms. To test this possibility in an upward-colonizing species, we artificially incubated developing embryos of the viperine snake (Natrix maura) using a split-clutch design, in conditions of extreme high elevation (hypoxia at 2877 m above sea level; 72% sea-level equivalent O2 availability) or low elevation (control group; i.e. normoxia at 436 m above sea level). Hatching success did not differ between the two treatments. Embryos developing at extreme high elevation had higher heart rates and hatched earlier, resulting in hatchlings that were smaller in body size and slower swimmers compared to their siblings incubated at lower elevation. Furthermore, post-hatching reciprocal transplant of juveniles showed that snakes which developed at extreme high elevation, when transferred back to low elevation, did not recover full performance compared to their siblings from the low elevation incubation treatment. These results suggest that incubation at extreme high elevation, including the effects of hypoxia, will not prevent oviparous ectotherms from producing viable young, but may pose significant physiological challenges on developing offspring in ovo. These early-life performance limitations imposed by extreme high elevation could have negative consequences on adult phenotypes, including on fitness-related traits.


Assuntos
Altitude , Colubridae/embriologia , Oxigênio , Adaptação Fisiológica , Animais , Tamanho Corporal , Colubridae/fisiologia , Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário/fisiologia , Feminino , Frequência Cardíaca , Masculino , Natação/fisiologia
8.
Mol Ecol ; 29(15): 2904-2921, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32563209

RESUMO

Historical factors (colonization scenarios, demographic oscillations) and contemporary processes (population connectivity, current population size) largely contribute to shaping species' present-day genetic diversity and structure. In this study, we use a combination of mitochondrial and nuclear DNA markers to understand the role of Quaternary climatic oscillations and present-day gene flow dynamics in determining the genetic diversity and structure of the newt Calotriton asper (Al. Dugès, 1852), endemic to the Pyrenees. Mitochondrial DNA did not show a clear phylogeographic pattern and presented low levels of variation. In contrast, microsatellites revealed five major genetic lineages with admixture patterns at their boundaries. Approximate Bayesian computation analyses and linear models indicated that the five lineages likely underwent separate evolutionary histories and can be tracked back to distinct glacial refugia. Lineage differentiation started around the Last Glacial Maximum at three focal areas (western, central and eastern Pyrenees) and extended through the end of the Last Glacial Period in the central Pyrenees, where it led to the formation of two more lineages. Our data revealed no evidence of recent dispersal between lineages, whereas borders likely represent zones of secondary contact following expansion from multiple refugia. Finally, we did not find genetic evidence of sex-biased dispersal. This work highlights the importance of integrating past evolutionary processes and present-day gene flow and dispersal dynamics, together with multilocus approaches, to gain insights into what shaped the current genetic attributes of amphibians living in montane habitats.


Assuntos
Variação Genética , Refúgio de Vida Selvagem , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Repetições de Microssatélites/genética , Filogenia , Filogeografia , Salamandridae/genética
9.
Nat Ecol Evol ; 4(8): 1044-1059, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32451428

RESUMO

There is mounting evidence of species redistribution as climate warms. Yet, our knowledge of the coupling between species range shifts and isotherm shifts remains limited. Here, we introduce BioShifts-a global geo-database of 30,534 range shifts. Despite a spatial imbalance towards the most developed regions of the Northern Hemisphere and a taxonomic bias towards the most charismatic animals and plants of the planet, data show that marine species are better at tracking isotherm shifts, and move towards the pole six times faster than terrestrial species. More specifically, we find that marine species closely track shifting isotherms in warm and relatively undisturbed waters (for example, the Central Pacific Basin) or in cold waters subject to high human pressures (for example, the North Sea). On land, human activities impede the capacity of terrestrial species to track isotherm shifts in latitude, with some species shifting in the opposite direction to isotherms. Along elevational gradients, species follow the direction of isotherm shifts but at a pace that is much slower than expected, especially in areas with warm climates. Our results suggest that terrestrial species are lagging behind shifting isotherms more than marine species, which is probably related to the interplay between the wider thermal safety margin of terrestrial versus marine species and the more constrained physical environment for dispersal in terrestrial versus marine habitats.


Assuntos
Mudança Climática , Clima , Animais , Ecossistema , Oceanos e Mares , Plantas
10.
Sci Rep ; 10(1): 3570, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107433

RESUMO

Triturus cristatus and Triturus marmoratus are two protected and declining newts occurring in the administrative department of Vienne, in France. They have limited dispersal abilities and rely on the connectivity between habitats and their suitability. In a warming climate, the locations of suitable habitats are expected to change, as is the connectivity. Here, we wondered how climate change might affect shifts in habitat suitability and connectivity of habitat patches, as connectivity is a key element enabling species to realize a potential range shift. We used ecological niche modelling (ENM), combining large-scale climate suitability with local scale, high-resolution habitat features, to identify suitable areas for the two species, under low and high warming scenarios (RCP 2.6 and RCP 8.5). We associated it with connectivity assessment through graph theory. The variable 'small ponds' contributed most to land cover-only ENMs for both species. Projections with climate change scenarios revealed a potential impact of warming on suitable habitat patches for newts, especially for T. cristatus. We observed a decrease in connectivity following a decrease in patch suitability. Our results highlight the important areas for newt habitat connectivity within the study area, and define those potentially threatened by climate warming. We provide information for prioritizing sites for acquisition, protection or restoration, and to advise landscape policies. Our framework is a useful and easily reproducible way to combine global climate requirements of the species with detailed information on species habitats and occurrence when available.

11.
Ecol Evol ; 9(19): 11227-11231, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31641467

RESUMO

Nineteen polymorphic microsatellite loci were identified and developed for Natrix maura. Polymorphism was assessed for 120 individuals sampled across four sampling sites from the French Pyrenees Mountains. The number of alleles per locus ranged from 3 to 15, and expected heterozygosity per locus ranged from 0.227 to 0.863. We tested for deviation from Hardy-Weinberg equilibrium and linkage disequilibrium and assessed the presence of null alleles for all loci, resulting in a selection of 14 high-quality polymorphic markers. These markers will be extremely useful in identifying fine-scale genetic structures and providing insight into conservation management plans of this species.

12.
PeerJ ; 6: e6053, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643673

RESUMO

BACKGROUND: Inter-patch movements may lead to genetic mixing, decreasing both inbreeding and population extinction risks, and is hence a crucial aspect of amphibian meta-population dynamics. Traveling through heterogeneous landscapes might be particularly risky for amphibians. Understanding how these species perceive their environment and how they move in heterogeneous habitats is an essential step in explaining metapopulation dynamics and can be important for predicting species' responses to climate change and for conservation policy and management. METHODS: Using an experimental approach, the present study focused on the movement behavior (crossing speed and number of stops) on different substrates mimicking landscape components (human-made and natural substrates) in two amphibian species contrasting in locomotion mode: the common toad (Bufo bufo), a hopping and burrowing anuran and the marbled newt (Triturus marmoratus), a walking salamander. We tested the hypothesis that species reaction to substrate is dependent on specific ecological requirements or locomotion modes because of morphological and behavioral differences. RESULTS: In both species, substrate type influenced individual crossing speed, with individuals moving faster on soil than on concrete substrate. We also demonstrated that long-legged individuals moved faster than individuals with short legs. In both species, the number of stops was higher in females than in males. In common toads, the number of stops did not vary between substrates tested, whereas in marbled newts the number of stops was higher on concrete than on soil substrate. DISCUSSION: We highlighted that concrete substrate (mimicking roads) negatively affect the crossing speed of both studied species, with an effect potentially higher in marbled newts. Our findings corroborate negative effects of such heterogeneous landscapes on movement behavior of two amphibian species, which may have implications for the dynamics of metapopulations.

13.
Proc Natl Acad Sci U S A ; 115(47): 11988-11993, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30397109

RESUMO

Limited dispersal is classically considered as a prerequisite for ecological specialization to evolve, such that generalists are expected to show greater dispersal propensity compared with specialists. However, when individuals choose habitats that maximize their performance instead of dispersing randomly, theory predicts dispersal with habitat choice to evolve in specialists, while generalists should disperse more randomly. We tested whether habitat choice is associated with thermal niche specialization using microcosms of the ciliate Tetrahymena thermophila, a species that performs active dispersal. We found that thermal specialists preferred optimal habitats as predicted by theory, a link that should make specialists more likely to track suitable conditions under environmental changes than expected under the random dispersal assumption. Surprisingly, generalists also performed habitat choice but with a preference for suboptimal habitats. Since this result challenges current theory, we developed a metapopulation model to understand under which circumstances such a preference for suboptimal habitats should evolve. We showed that competition between generalists and specialists may favor a preference for niche margins in generalists under environmental variability. Our results demonstrate that the behavioral dimension of dispersal-here, habitat choice-fundamentally alters our predictions of how dispersal evolve with niche specialization, making dispersal behaviors crucial for ecological forecasting facing environmental changes.


Assuntos
Biota/fisiologia , Comportamento Competitivo/fisiologia , Tetrahymena thermophila/fisiologia , Animais , Evolução Biológica , Cilióforos/fisiologia , Ecossistema , Especialização , Especificidade da Espécie , Temperatura , Territorialidade
14.
J Therm Biol ; 77: 38-44, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30196897

RESUMO

Temperature affects the physiological functions of ectotherms. To maintain optimal body temperature and ensure physiological performance, these organisms can use behavioral adjustments to keep the body temperature in their specific temperature range, so-called preferred temperature (Tpref). It is therefore crucial to describe and understand how Tpref vary within and amongst populations to predict the effects of climate change of altitudinal range shifts in organisms. We aimed at determining the altitudinal variations in Tpref in three ectothermic species (the Pyrenean brook salamander - a semi-aquatic and thigmothermic amphibian - the European common lizard and the wall lizard - both heliothermic species). Using an experimental approach where Tpref were measured along a temperature gradient in laboratory conditions, we used a cross-sectional approach to compare the variation of Tpref measured in populations sampled along the altitudinal gradient in the Pyrenees. We hypothesized a complex and highly variable intra-specific response of Tpref along geographical clines, with a positive relationship between Tpref and altitude (as predicted by the countergradient variation), the reverse pattern (referring to the adaptation of local optima hypothesis), or no relationship at all. Our results corroborated partially the countergradient hypothesis in the salamander (middle to high elevation part). At high altitude level, individuals may compensate for lower opportunities of favorable conditions by choosing a high temperature which maximizes their activities. However, populations from low elevation level hence better supported the adaptation of local optima hypothesis, such as both lizard species, for which Tpref tended instead to decrease with altitude. Lizards from cold climates may be physiologically adapted to low temperature, with the ability to reach optimal functioning at lower temperature than individuals from low altitude. Our findings suggest that predicting future niche models should therefore take into account the variability of Tpref, where species might be differently affected by global warming.


Assuntos
Aclimatação , Altitude , Regulação da Temperatura Corporal , Lagartos/fisiologia , Urodelos/fisiologia , Animais , Temperatura Corporal , Mudança Climática , Clima Frio , Feminino , Aquecimento Global , Masculino , Especificidade da Espécie
15.
Bioconjug Chem ; 27(10): 2281-2286, 2016 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-27706941

RESUMO

Chemoselective functionalization of peptides and proteins to selectively introduce residues for detection, capture, or specific derivatization is of high interest to the synthetic community. Here we report a new method for the mild and effective mono-iodination of tyrosine residues in fully unprotected peptides. This method is highly chemoselective and compatible with a wide variety of functional groups. The introduced iodine can subsequently serve as a handle for further functionalization such as introduction of fluorescent dyes and thus be used for chemoselective labeling of isolated peptides.

16.
Proc Biol Sci ; 283(1839)2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27683371

RESUMO

The existence of dispersal syndromes contrasting disperser from resident phenotypes within populations has been intensively documented across taxa. However, how such suites of phenotypic traits emerge and are maintained is largely unknown, although deciphering the processes shaping the evolution of dispersal phenotypes is a key in ecology and evolution. In this study, we created artificial populations of a butterfly, in which we controlled for individual phenotypes and measured experimentally the roles of selection and genetic constraints on the correlations between dispersal-related traits: flight performance and wing morphology. We demonstrate that (i) trait covariations are not due to genetic correlations, (ii) the effects of selection are sex-specific, and (iii) both divergent and stabilizing selection maintain specific flight performance phenotypes and wing morphologies. Interestingly, some trait combinations are also favoured, depending on sex and fitness components. Moreover, we provide evidence for the role of (dis)assortative mating in the evolution of these dispersal-related traits. Our results suggest that dispersal syndromes may have high evolutionary potential, but also that they may be easily disrupted under particular environmental conditions.

17.
Nat Commun ; 7: 12643, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27561410

RESUMO

Biodiversity changes are lagging behind current climate warming. The underlying determinants of this climatic debt are unknown and yet critical to understand the impacts of climate change on the present biota and improve forecasts of biodiversity changes. Here we assess determinants of climatic debt accumulated in French forest herbaceous plant communities between 1987 and 2008 (that is, a 1.05 °C mean difference between the observed and bioindicated temperatures). We show that warmer baseline conditions predispose plant communities to larger climatic debts, and that climate warming exacerbates this response. Forest plant communities, however, are absorbing part of the temperature increase mainly through the species' ability to tolerate changing climate. As climate warming is expected to accelerate during the twenty-first century, plant migration and tolerance to climatic stresses probably will be insufficient to absorb this impact posing threats to the sustainability of forest plant communities.


Assuntos
Biodiversidade , Mudança Climática , Florestas , Temperatura Alta/efeitos adversos , Fenômenos Fisiológicos Vegetais , Termotolerância/fisiologia
18.
J Labelled Comp Radiopharm ; 59(14): 604-610, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27282912

RESUMO

Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of ß-cells in vivo is expected to contribute to an improved understanding of the underlying pathophysiology, improved diagnosis, and development of new treatment options for diabetes. Here, we describe the first radiosyntheses of [3 H]-TAK875 and [18 F]-TAK875 derivatives to be used as ß-cell imaging probes addressing the free fatty acid receptor 1 (FFAR1/GPR40). The fluorine-labeled derivative showed similar agonistic activity as TAK875 in a functional assay. The radiosynthesis of the 18 F-labelled tracer 2a was achieved with 16.7 ± 5.7% radiochemical yield in a total synthesis time of 60-70 min.


Assuntos
Benzofuranos/síntese química , Benzofuranos/metabolismo , Radioisótopos de Flúor , Células Secretoras de Insulina/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores Acoplados a Proteínas G/metabolismo , Sulfonas/síntese química , Sulfonas/metabolismo , Trítio , Benzofuranos/química , Benzofuranos/farmacocinética , Técnicas de Química Sintética , Células HEK293 , Humanos , Sulfonas/química , Sulfonas/farmacocinética
19.
ACS Chem Biol ; 11(6): 1745-54, 2016 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-27115176

RESUMO

Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of ß-cells bears the potential to contribute to an improved understanding, diagnosis, and development of new treatment options for diabetes. Here, we describe the first small molecule fluorescent probe targeting the free fatty acid receptor 1 (FFAR1/GPR40). This receptor is highly expressed on ß-cells, and was up to now unexplored for imaging purposes. We designed a novel probe by facile modification of the selective and potent FFAR1 agonist TAK-875. Effective and specific binding of the probe was demonstrated using FFAR1 overexpressing cells. We also successfully labeled FFAR1 on MIN6 and INS1E cells, two widely used ß-cell models, by applying an effective amplification protocol. Finally, we showed that the probe is capable of inducing insulin secretion in a glucose-dependent manner, thus demonstrating that functional activity of the probe was maintained. These results suggest that our probe represents a first important step to successful ß-cell imaging by targeting FFAR1. The developed probe may prove to be particularly useful for in vitro and ex vivo studies of diabetic cellular and animal models to gain new insights into disease pathogenesis.


Assuntos
Corantes Fluorescentes/química , Receptores Acoplados a Proteínas G/metabolismo , Animais , Benzofuranos/química , Benzofuranos/farmacologia , Diabetes Mellitus/diagnóstico por imagem , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Células HEK293 , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Camundongos , Imagem Molecular , Ratos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Relação Estrutura-Atividade , Sulfonas/química , Sulfonas/farmacologia
20.
Nature ; 479(7374): 517-20, 2011 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-22012261

RESUMO

Climate change is driving latitudinal and altitudinal shifts in species distribution worldwide, leading to novel species assemblages. Lags between these biotic responses and contemporary climate changes have been reported for plants and animals. Theoretically, the magnitude of these lags should be greatest in lowland areas, where the velocity of climate change is expected to be much greater than that in highland areas. We compared temperature trends to temperatures reconstructed from plant assemblages (observed in 76,634 surveys) over a 44-year period in France (1965-2008). Here we report that forest plant communities had responded to 0.54 °C of the effective increase of 1.07 °C in highland areas (500-2,600 m above sea level), while they had responded to only 0.02 °C of the 1.11 °C warming trend in lowland areas. There was a larger temperature lag (by 3.1 times) between the climate and plant community composition in lowland forests than in highland forests. The explanation of such disparity lies in the following properties of lowland, as compared to highland, forests: the higher proportion of species with greater ability for local persistence as the climate warms, the reduced opportunity for short-distance escapes, and the greater habitat fragmentation. Although mountains are currently considered to be among the ecosystems most threatened by climate change (owing to mountaintop extinction), the current inertia of plant communities in lowland forests should also be noted, as it could lead to lowland biotic attrition.


Assuntos
Biota , Aquecimento Global/estatística & dados numéricos , Plantas , Árvores , Altitude , França , História do Século XX , História do Século XXI , Modelos Biológicos , Temperatura , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...