Multiple glacial refugia and contemporary dispersal shape the genetic structure of an endemic amphibian from the Pyrenees

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.info:eu-repo/semantics/publishedVersio

Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia

Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population

High temperatures limit developmental resilience to high-elevation hypoxia in the snake Natrix maura (Squamata: Colubridae)

International audienceClimate change is generating range shifts in many organisms, notably along the altitudinal gradient. However, moving up in altitude exposes organisms to lower oxygen availability, which may negatively affect development and fitness, especially at high temperatures. To test this possibility in a potentially upward-colonizing species, we artificially incubated developing embryos of the viperine snake Natrix maura Linnaeus 1758, using a split-clutch design, in conditions of extreme high elevation or low elevation at two ecologically-relevant incubation temperatures (24 and 32 °C). Embryos at low and extreme high elevations incubated at cool temperatures did not differ in development time, hatchling phenotype or locomotor performance. However, at the warmer incubation temperature and at extreme high elevation, hatching success was reduced. Further, embryonic heart rates were lower, incubation duration longer and juveniles born smaller. Nonetheless, snakes in this treatment were faster swimmers than siblings in other treatment groups, suggesting a developmental trade-off between size and performance. Constraints on development may be offset by the maintenance of important performance metrics, thus suggesting that early life-history stages will not prevent the successful colonization of high-elevation habitat even under the dual limitations of reduced oxygen and increased temperature

Presence of the Fungus B. dendrobatidis, but not B. salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

International audienceIn the last 20 years, the emergence of chytridiomycosis due to the chytrid fungi Batrachochytrium dendrobatidis (Bd), and the more recently described Batrachochytrium salamandrivorans (Bsal), has caused severe amphibian population regressions across the planet (Bosch et al. 2001; Spitzen-van der Sluijs et al. 2016; Scheele et al. 2019). This has generated an increase in scientific interest to decipher the complex interaction between the environment, the fungus and amphibian hosts, and increased surveillance efforts in many localities (Canessa et al. 2020). Batrachochytrium spp. affect the vital function of the amphibian skin, leading to lethargy or skin discoloration, hyperkeratosis, erosions (even ulcerations in Bsal) of the epidermis, and eventually death (Berger et al. 1998; Weldon et al. 2004; Stuart et al. 2004; Wake and Vredenburg 2010; Martel et al. 2013). Bd is currently found on all continents where amphibians are present (Skerratt et al. 2007), affecting more than 700 species within the three orders of amphibians and has been considered a major threat to amphibian biodiversity worldwide (Crawford et al. 2010; Fisher et al. 2012; Olson et al. 2013; Olson and Ronnenberg 2014)

Therapeutic potential of extracellular vesicles derived from cardiac progenitor cells in rodent models of chemotherapy-induced cardiomyopathy

International audienceBackground Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity. Methods Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9–11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography. Results In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice ( p = 0.043, p = 0.042, p = 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls. Conclusions Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM

Extracellular vesicles fail to trigger the generation of new cardiomyocytes in chronically infarcted hearts

Background: Extracellular vesicles (EV) mediate the therapeutic effects of stem cells but it is unclear whether this involves cardiac regeneration mediated by endogenous cardiomyocyte proliferation.Methods: Bi-transgenic MerCreMer/ZEG (n = 15/group) and Mosaic Analysis With Double Markers (MADM; n = 6/group) mouse models underwent permanent coronary artery ligation and received, 3 weeks later, 10 billion EV (from human iPS-derived cardiovascular progenitor cells [CPC]), or saline, injected percutaneously under echo guidance in the peri-infarcted myocardium. Endogenous cardiomyocyte proliferation was tracked by EdU labeling and biphoton microscopy. Other end points, including cardiac function (echocardiography and MRI), histology and transcriptomics were blindly assessed 4-6 weeks after injections.Results: There was no proliferation of cardiomyocytes in either transgenic mouse strains. Nevertheless, EV improved cardiac function in both models. In MerCreMer/ZEG mice, LVEF increased by 18.3 +/- 0.2% between baseline and the end-study time point in EV-treated hearts which contrasted with a decrease by 2.3 +/- 0.2% in the PBS group; MADM mice featured a similar pattern as intra-myocardial administration of EV improved LVEF by 13.3 +/- 0.16% from baseline whereas it decreased by 14.4 +/- 0.16% in the control PBS-injected group. This functional improvement was confirmed by MRI and associated with a reduction in infarct size, the decreased expression of several pro-fibrotic genes and an overexpression of the anti-fibrotic mi RNA 133-al compared to controls. Experiments with an anti-miR133-a demonstrated that the cardio-reparative effects of EV were partly abrogated.Conclusions: EV-CPC do not trigger cardiomyocyte proliferation but still improve cardiac function by other mechanisms which may include the regulation of fibrosis

Presence of the Fungus Batrachochytrium dendrobatidis, but not Batrachochytrium salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

Este artículo contiene 6 páginas, 12 tabla, 2 figuras.This work was supported by the French Laboratory of Excellence project TULIP (ANR-10-LABX-41; ANR-11-IDEX-0002-02) by the INTERREG POCTEFA ECTOPYR (no. EFA031/15) and by the LIFE+ LIMNOPIRINEUS (LIFE13 NAT/ ES1210) projects.Peer reviewe

Presence of the Fungus B. dendrobatidis, but not B. salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

International audienceIn the last 20 years, the emergence of chytridiomycosis due to the chytrid fungi Batrachochytrium dendrobatidis (Bd), and the more recently described Batrachochytrium salamandrivorans (Bsal), has caused severe amphibian population regressions across the planet (Bosch et al. 2001; Spitzen-van der Sluijs et al. 2016; Scheele et al. 2019). This has generated an increase in scientific interest to decipher the complex interaction between the environment, the fungus and amphibian hosts, and increased surveillance efforts in many localities (Canessa et al. 2020). Batrachochytrium spp. affect the vital function of the amphibian skin, leading to lethargy or skin discoloration, hyperkeratosis, erosions (even ulcerations in Bsal) of the epidermis, and eventually death (Berger et al. 1998; Weldon et al. 2004; Stuart et al. 2004; Wake and Vredenburg 2010; Martel et al. 2013). Bd is currently found on all continents where amphibians are present (Skerratt et al. 2007), affecting more than 700 species within the three orders of amphibians and has been considered a major threat to amphibian biodiversity worldwide (Crawford et al. 2010; Fisher et al. 2012; Olson et al. 2013; Olson and Ronnenberg 2014)