Integrating data‐deficient species in analyses of evolutionary history loss

There is an increasing interest in measuring loss of phylogenetic diversity and evolutionary distinctiveness which together depict the evolutionary history of conservation interest. Those losses are assessed through the evolutionary relationships between species and species threat status or extinction probabilities. Yet, available information is not always sufficient to quantify the threat status of species that are then classified as data deficient. Data‐deficient species are a crucial issue as they cause incomplete assessments of the loss of phylogenetic diversity and evolutionary distinctiveness. We aimed to explore the potential bias caused by data‐deficient species in estimating four widely used indices: HEDGE, EDGE, PDloss, and Expected PDloss. Second, we tested four different widely applicable and multitaxa imputation methods and their potential to minimize the bias for those four indices. Two methods are based on a best‐ vs. worst‐case extinction scenarios, one is based on the frequency distribution of threat status within a taxonomic group and one is based on correlates of extinction risks. We showed that data‐deficient species led to important bias in predictions of evolutionary history loss (especially high underestimation when they were removed). This issue was particularly important when data‐deficient species tended to be clustered in the tree of life. The imputation method based on correlates of extinction risks, especially geographic range size, had the best performance and enabled us to improve risk assessments. Solving threat status of DD species can fundamentally change our understanding of loss of phylogenetic diversity. We found that this loss could be substantially higher than previously found in amphibians, squamate reptiles, and carnivores. We also identified species that are of high priority for the conservation of evolutionary distinctiveness.     

Design,synthesis, biological evaluation and cellular imaging of imidazo[4,5-b]pyridine derivatives as potent and selective TAM inhibitors

The TAM kinase family arises as a new effective and attractive therapeutic target for cancer therapy, autoimmune and viral diseases. A series of 2,6-disubstituted imidazo[4,5-b]pyridines were designed, synthesized and identified as highly potent TAM inhibitors. Despite remarkable structural similarities within the TAM family, compounds 28 and 25 demonstrated high activity and selectivity in vitro against AXL and MER, with IC₅₀ value of 0.77?nM and 9?nM respectively and a 120- to 900-fold selectivity. We also observed an unexpected nuclear localization for compound 10Bb, thanks to nanoSIMS technology, which could be correlated to the absence of cytotoxicity on three different cancer cell lines being sensitive to TAM inhibition.     

Gene Disruption in <Emphasis Type="Italic">Scedosporium aurantiacum</Emphasis>: Proof of Concept with the Disruption of <Emphasis Type="Italic">SODC</Emphasis> Gene Encoding a Cytosolic Cu,Zn-Superoxide Dismutase

Scedosporium species are opportunistic pathogens responsible for a large variety of infections in humans. An increasing occurrence was observed in patients with underlying conditions such as immunosuppression or cystic fibrosis. Indeed, the genus Scedosporium ranks the second among the filamentous fungi colonizing the respiratory tracts of the CF patients. To date, there is very scarce information on the pathogenic mechanisms, at least in part because of the limited genetic tools available. In the present study, we successfully developed an efficient transformation and targeted gene disruption approach on the species Scedosporium aurantiacum. The disruption cassette was constructed using double-joint PCR procedure, and resistance to hygromycin B as the selection marker. This proof of concept was performed on the functional gene SODC encoding the Cu,Zn-superoxide dismutase. Disruption of the SODC gene improved susceptibility of the fungus to oxidative stress. This technical advance should open new research areas and help to better understand the biology of Scedosporium species.     

Sex identification in King Penguins Aptenodytes patagonicus through morphological and acoustic cues

In the context of sexual selection, animals have developed a variety of cues conveying information about the sex of an individual to conspecifics. In many colonial seabird species, where females and males are monomorphic and do not show obvious differences in external morphology, acoustic cues are an important signal for individual and sex recognition. Here, we study the vocal and morphological sex dimorphism in the King Penguin Aptenodytes patagonicus, a colonial, monomorphic seabird for which our knowledge about the role of vocalizations and morphology in mate choice is very limited. Data were collected at Possession Island, Crozet Archipelago, in a breeding colony consisting of about 16 000 breeding pairs. Using measurements of six morphological features and analysing acoustic parameters of call recordings of adult individuals, we show that King Penguins can be sexed based on a single morphological measurement of the beak with an accuracy of 79%. We found a sex‐specific syntax in adult King Penguin calls that provided a 100% accurate method to distinguish between the sexes in our study population. To confirm the method at the species level, we analysed calls recorded from King Penguin adults in Kerguelen Island, 1300 km away from our study population and found the same accuracy of the sex‐specific syntax. This sex‐specific syllable arrangement is rare in non‐passerines and is a first step in understanding the mate choice process in this species. Furthermore, it offers a cost‐effective, non‐invasive technique for researchers to sex King Penguins in the field.     

Comparative biometry and isotopy of three dominant pennatulacean corals in the Northwest Atlantic

Spatial and temporal shifts in biometric features were examined in three common deep‐water pennatulacean corals (sea pens) from the Northwest Atlantic: Anthoptilum grandiflorum, Halipteris finmarchica and Pennatula aculeata. These three species show different morphological characters and adaptations to their environment. Analyses of colony length, ratio of peduncle to colony length, weight/length ratio, polyp size and density as well as sclerite shape, location and abundance indicate that their phenotype is modulated by environmental factors (e.g. food availability, currents and sediment type) and antipredator strategies. Moreover, the three species had different carbon and nitrogen stable isotope signatures that could be explain primarily by their different polyp diameters and colony shapes, suggesting that they rely on slightly different food sources (varying proportions of phytodetritus and zooplankton). Finally, sclerites were found only in H. finmarchica and P. aculeata and are not known to occur in A. grandiflorum, except for minute oval bodies inside the peduncle. The Mg/Ca ratio of sclerites differed between the two species and, for P. aculeata, among types of sclerites, evoking different biomineralization pathways related to their functional roles (structural support or defence). Overall, this study provides new information on the ecology of poorly known species, which are ubiquitous and suspected to play an important ecological role in deep‐water ecosystems.     

Atopic dermatitis induces the expansion of thymus‐derived regulatory T cells exhibiting a Th2‐like phenotype in mice

Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper‐responsiveness of the skin and environmental factors. Although the important role of abnormal immune reactivity in the pathogenesis of AD is widely accepted, the role of regulatory T cells (T_regs) remains elusive. We found that the T_reg population is expanded in a mouse model of AD, i.e. mice topically treated with vitamin D3 (VitD). Moreover, mice with AD‐like symptoms exhibit increased inducible T‐cell costimulator (ICOS)‐, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4)‐ and Glycoprotein‐A repetitions predominant receptor (GARP)‐expressing T_regs in skin‐draining lymph nodes. Importantly, the differentiation of T_regs into thymus‐derived T_regs is favoured in our mouse model of AD. Emigrated skin‐derived dendritic cells are required for T_reg induction and Langerhans cells are responsible for the biased expansion of thymus‐derived T_regs. Intriguingly, thymus‐derived T_regs isolated from mice with AD‐like symptoms exhibit a Th2 cytokine profile. Thus, AD might favour the expansion of pathogenic T_regs able to produce Th2 cytokines and to promote the disease instead of alleviating symptoms.     

Identification of class II ADP‐ribosylation factors as cellular factors required for hepatitis C virus replication

GBF1 is a host factor required for hepatitis C virus (HCV) replication. GBF1 functions as a guanine nucleotide exchange factor for G‐proteins of the Arf family, which regulate membrane dynamics in the early secretory pathway and the metabolism of cytoplasmic lipid droplets. Here we established that the Arf‐guanine nucleotide exchange factor activity of GBF1 is critical for its function in HCV replication, indicating that it promotes viral replication by activating one or more Arf family members. Arf involvement was confirmed with the use of two dominant negative Arf1 mutants. However, siRNA‐mediated depletion of Arf1, Arf3 (class I Arfs), Arf4 or Arf5 (class II Arfs), which potentially interact with GBF1, did not significantly inhibit HCV infection. In contrast, the simultaneous depletion of both Arf4 and Arf5, but not of any other Arf pair, imposed a significant inhibition of HCV infection. Interestingly, the simultaneous depletion of both Arf4 and Arf5 had no impact on the activity of the secretory pathway and induced a compaction of the Golgi and an accumulation of lipid droplets. A similar phenotype of lipid droplet accumulation was also observed when GBF1 was inhibited by brefeldin A. In contrast, the simultaneous depletion of both Arf1 and Arf4 resulted in secretion inhibition and Golgi scattering, two actions reminiscent of GBF1 inhibition. We conclude that GBF1 could regulate different metabolic pathways through the activation of different pairs of Arf proteins.