Crosstalk Between LXR and Caveolin-1 Signaling Supports Cholesterol Efflux and Anti-Inflammatory Pathways in Macrophages

© 2021 Ramírez, Torrecilla-Parra, Pardo-Marqués, de-Frutos, Pérez-García, Tabraue, de la Rosa, Martín-Rodriguez, Díaz-Sarmiento, Nuñez, Orizaola, Través, Camps, Boscá and Castrillo.Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis.We thank MINECO FPI predoctoral fellowship granted to MCO (BES-2015-075339). Experimental work was supported by grants from Ministerio de Ciencia, Investigación y Universidades, y Fondo Europeo de Desarrollo Regional (FEDER) Grant REF: PID2019-104284RB-I00/AEI/10.13039/501100011033 (to AC) and support from Networks of Excellence from MINECO (Nuclear Receptors in Cancer, Metabolism and Inflammation [NuRCaMeIn] SAF2017-90604-REDT to AC. Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional (to LB). Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación 2018 (RTI2018-095061-B-I00); TALENTO Grant from Madrid Government, Spain (2017-T1/BMD-5333); Consejería de Ciencia, Universidades e Innovación Comunidad de Madrid, Spain (PEJD-2018-POST/BMD-8900 and PEDJ-2018-AI/BDM-9724) to CMR

Mothers Matter Too: Benefits of Temperature Oviposition Preferences in Newts

The maternal manipulation hypothesis states that ectothermic females modify thermal conditions during embryonic development to benefit their offspring (anticipatory maternal effect). However, the recent theory suggests that the ultimate currency of an adaptive maternal effect is female fitness that can be maximized also by decreasing mean fitness of individual offspring. We evaluated benefits of temperature oviposition preferences in Alpine newts (Ichthyosaura [formerly Triturus] alpestris) by comparing the thermal sensitivity of maternal and offspring traits across a range of preferred oviposition temperatures (12, 17, and 22°C) and by manipulating the egg-predation risk during oviposition in a laboratory thermal gradient (12–22°C). All traits showed varying responses to oviposition temperatures. Embryonic developmental rates increased with oviposition temperature, whereas hatchling size and swimming capacity showed the opposite pattern. Maternal oviposition and egg-predation rates were highest at the intermediate temperature. In the thermal gradient, females oviposited at the same temperature despite the presence of caged egg-predators, water beetles (Agabus bipustulatus). We conclude that female newts prefer a particular temperature for egg-deposition to maximize their oviposition performance rather than offspring fitness. The evolution of advanced reproductive modes, such as prolonged egg-retention and viviparity, may require, among others, the transition from selfish temperature preferences for ovipositon to the anticipatory maternal effect

Genetic correlations between temperature-induced plasticity of life-history traits in a soil arthropod.

Temperature is considered one of the most important mediators of phenotypic plasticity in ectotherms. However, the costs and benefits shaping the evolution of different thermal responses are poorly elucidated. One of the possible constraints to phenotypic plasticity is its intrinsic genetic cost, such as genetic linkage or pleiotropy. Genetic coupling of the thermal response curves for different life history traits may significantly affect the evolution of thermal sensitivity in thermally fluctuating environments. We used the collembolan Orchesella cincta to study if there is genetic variation in temperature-induced phenotypic plasticity in life history traits, and if the degree of temperature-induced plasticity is correlated across traits. Egg development rate, juvenile growth rate and egg size of 19 inbred isofemale lines were measured at two temperatures. Our results show that temperature was a highly significant factor for all three traits. Egg development rate and juvenile growth rate increased with increasing temperature, while egg size decreased. Line by temperature interaction was significant for all traits tested; indicating that genetic variation for temperature-induced plasticity existed. The degree of plasticity was significantly positively correlated between egg development rate and growth rate, but plasticity in egg size was not correlated to the other two plasticity traits. The findings suggest that the thermal plasticities of egg development rate and growth rate are partly under the control of the same genes or genetic regions. Hence, evolution of the thermal plasticity of traits cannot be understood in isolation of the response of other traits. If traits have similar and additive effects on fitness, genetic coupling between these traits may well facilitate the evolution of optimal phenotypes. However, for this we need to know the selective forces under field conditions. © 2010 Springer Science+Business Media B.V

Recovery of high mountain Alpine lakes after the eradication of introduced brook trout Salvelinus fontinalis using non-chemical methods

The final publication is available at Springer via http://dx.doi.org/10.1007/s10530-018-1867-0Fish stocking is a serious threat to originally fishless mountain lakes. We used non-chemical eradication methods (i.e. gillnetting and electrofishing) in four high mountain lakes in the Gran Paradiso National Park (Western Italian Alps) to eradicate alien brook trout Salvelinus fontinalis. Data of amphibians, macroinvertebrates, zooplankton, chlorophyll-a, nutrient concentrations, and water transparency were used as indicators of the recovery process. All treated lakes were returned to their original fishless condition in spite of their different sizes and habitat complexity, without permanent negative side-effects for native species. Several ecological indicators showed that many impacts of introduced fish can be reversed over a short time period following eradication. The present study adds to a still growing body of specialized literature on the recovery of habitats after the eradication of alien species and provides further evidence that physical eradication methods are effective and can be part of a more general strategy for the conservation of high mountain lake biota

Why Should We Preserve Fishless High Mountain Lakes?

High mountain lakes are originally fishless, although many have had introductions of non-native fish species, predominantly trout, and recently also minnows introduced by fishermen that use them as live bait. The extent of these introductions is general and substantial often involving many lakes over mountain ranges. Predation on native fauna by introduced fish involves profound ecological changes since fish occupy a higher trophic level that was previously inexistent. Fish predation produces a drastic reduction or elimination of autochthonous animal groups, such as amphibians and large macroinvertebrates in the littoral, and crustaceans in the plankton. These strong effects raise concerns for the conservation of high mountain lakes. In terms of individual species, those adapted to live in larger lakes have suffered a higher decrease in the size of their metapopulation. This ecological problem is discussed from a European perspective providing examples from two study areas: the Pyrenees and the Western Italian Alps. Species-specific studies are urgently needed to evaluate the conservation status of the more impacted species, together with conservation measures at continental and regional scales, through regulation, and at local scale, through restoration actions, aimed to stop further invasive species expansions and to restore the present situation. At different high mountain areas of the world, there have been restoration projects aiming to return lakes to their native fish-free status. In these areas autochthonous species that disappeared with the introduction of fish are progressively recovering their initial distribution when nearby fish-free lakes and ponds are available

Exotic fish in exotic plantations: a multi-scale approach to understand amphibian occurrence in the mediterranean region

Globally, amphibian populations are threatened by a diverse range of factors including habitat destruction and alteration. Forestry practices have been linked with low diversity and abundance of amphibians. The effect of exotic Eucalyptus spp. plantations on amphibian communities has been studied in a number of biodiversity hotspots, but little is known of its impact in the Mediterranean region. Here, we identify the environmental factors influencing the presence of six species of amphibians (the Caudata Pleurodeles waltl, Salamandra salamandra, Lissotriton boscai, Triturus marmoratus and the anurans Pelobates cultripes and Hyla arborea/meridionalis) occupying 88 ponds. The study was conducted in a Mediterranean landscape dominated by eucalypt plantations alternated with traditional use (agricultural, montados and native forest) at three different scales: local (pond), intermediate (400 metres radius buffer) and broad (1000 metres radius buffer). Using the Akaike Information Criterion for small samples (AICc), we selected the top-ranked models for estimating the probability of occurrence of each species at each spatial scale separately and across all three spatial scales, using a combination of covariates from the different magnitudes. Models with a combination of covariates at the different spatial scales had a stronger support than those at individual scales. The presence of predatory fish in a pond had a strong effect on Caudata presence. Permanent ponds were selected by Hyla arborea/meridionalis over temporary ponds. Species occurrence was not increased by a higher density of streams, but the density of ponds impacted negatively on Lissotriton boscai. The proximity of ponds occupied by their conspecifics had a positive effect on the occurrence of Lissotriton boscai and Pleurodeles waltl. Eucalypt plantations had a negative effect on the occurrence of the newt Lissotriton boscai and anurans Hyla arborea/meridionalis, but had a positive effect on the presence of Salamandra salamandra, while no effect on any of the other species was detected. In conclusion, eucalypts had limited effects on the amphibian community at the intermediate and broad scales, but predatory fish had a major impact when considering all the scales combined. The over-riding importance of introduced fish as a negative impact suggests that forest managers should prevent new fish introductions and eradicate fish from already-occupied ponds whenever possible

Exposure to ionizing radiation and liver histopathology in the tree frogs of Chornobyl (Ukraine)

Ionizing radiation has the potential to damage organic molecules and decrease the health and survival of wildlife. The accident at the Chornobyl Nuclear Plant (Ukraine, 1986) led to the largest release of radioactive material to the environment. Among the different organs of a vertebrate, the liver plays a crucial role in detoxification processes, and has been used as a biomarker to investigate cellular damage in ecotoxicological research. Here, we examined the impact of the exposure to the current levels of ionizing radiation present in the Chornobyl Exclusion Zone on the liver of Eastern tree frogs (Hyla orientalis). We quantified the area of melanomacrophage cells and morphological variables of hepatocytes, two cell types often used to estimate damage caused by pollutants in vertebrates. First, we investigated whether these hepatic parameters were indicative of frog (individual) condition. Then, we analyzed the effect of individual absorbed dose rates and ambient radiation levels on frog livers. Most of the studied parameters were correlated with individual body condition (a good predictor of amphibian fitness and survival). We did not detect marked morphological lesions in the liver of frogs captured in medium-high radiation environments. The area occupied by melanomacrophages and the morphology of hepatocytes did not change across a gradient of radiocontamination covering two orders of magnitude. Once accounting for body condition and sampling locality, the area of melanomacrophages was lower in areas with high radiation levels. Finally, the area occupied by melanomacrophages was not linked to dorsal skin coloration. Our results indicate that current levels of radiation experienced by tree frogs in Chornobyl do not cause histopathological damage in their liver. These results agree with previous physiological work in the species in the Chornobyl area, and encourage further molecular and physiological research to fully disentangle the current impact of the Chornobyl accident on wildlife

Long-distance travellers stopover for longer: a case study with spoonbills staying in North Iberia

International audienceLong-distance migration is widespread among birds, connecting breeding and wintering areas through a set of stopover localities where individuals refuel and/or rest. The extent of the stopover is critical in determining the migratory strategy of a bird. Here, we examined the relationship between minimum length of stay of PVC-ringed birds in a major stopover site and the remaining flight distance to the overwintering area in the Eurasian spoonbill () during four consecutive autumn migrations. We also analysed the potential effect of timing (arrival date), as well as the role of experience in explaining stopover duration of spoonbills. Overall, birds wintering in Africa, and facing long-distance travel from the stopover site (ca. 3,000 km) stay for longer (2.7 ± 0.4 days) than Iberian winterers (1.5 ± 0.2 days) that perform a much shorter migration (ca. 800 km). These differences were consistent between years. Stopover duration was not significantly affected by the age of the bird. However, there was a significant reduction as migration advanced. Our results suggest that spoonbills develop different stopover strategies depending on the expected distance to the wintering grounds. Adults, especially long-distance migratory ones, could reduce the potential negative effects of density-dependence processes by avoiding stopover at the end of the migration period. These findings are of significant relevance for understanding differences in migratory behaviour within single populations, especially for declining waterbirds, as well as stress the relevance of preserving stopover localities for the conservation of intraspecific diversity in migratory species