Reconstructing the origins of high-alpine niches and cushion life form in the genus Androsace S.L. (Primulaceae)

Relatively, few species have been able to colonize extremely cold alpine environments. We investigate the role played by the cushion life form in the evolution of climatic niches in the plant genus Androsace s.l., which spreads across the mountain ranges of the Northern Hemisphere. Using robust methods that account for phylogenetic uncertainty, intraspecific variability of climatic requirements and different life-history evolution scenarios, we show that climatic niches of Androsace s.l. exhibit low phylogenetic signal and that they evolved relatively recently and punctually. Models of niche evolution fitted onto phylogenies show that the cushion life form has been a key innovation providing the opportunity to occupy extremely cold environments, thus contributing to rapid climatic niche diversification in the genus Androsace s.l. We then propose a plausible scenario for the adaptation of plants to alpine habitats.     

The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses

Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.     

RhoA/ROCK I signalling downstream of the P2Y13 ADP-receptor controls HDL endocytosis in human hepatocytes

Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ectopic F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. However, P2Y(13)-dependent signalling pathway has never been described yet. The current study demonstrates a major role of cytoskeleton reorganization in F(1)-ATPase/P2Y(13)-dependent HDL endocytosis under the control of the small GTPase RhoA and its effector ROCK I. Indeed human hepatocytes (HepG(2) cells) stimulated by ADP or AR-C69931MX (both P2Y(13) agonists) showed a high specific activation of RhoA; in addition, inhibition of Rho proteins by C3 exoenzyme impairs HDL endocytosis whereas a constitutively active form of RhoA stimulates HDL endocytosis at the same level as under F(1)-ATPase/P2Y(13) activation. Pharmacological inhibition of ROCK activity decreased HDL endocytosis following stimulation by apoA-I (F(1)-ATPase ligand), ADP or AR-C69931MX and specific siRNA ROCK I extinction prevented the stimulation of HDL endocytosis without effect of ROCK II extinction. The functional involvement of ROCK I downstream F(1)-ATPase/P2Y(13) was confirmed by the strong enrichment of the membrane fraction in ROCK I and by the requirement of actin polymerization in hepatocyte HDL endocytosis. These results allow the identification of the molecular events downstream P2Y(13) receptor activation for a better understanding of hepatocyte HDL endocytosis, the latest step in reverse cholesterol transport.     

Tempo and mode of morphological evolution are decoupled from latitude in birds

The latitudinal diversity gradient is one of the most striking patterns in nature, yet its implications for morphological evolution are poorly understood. In particular, it has been proposed that an increased intensity of species interactions in tropical biota may either promote or constrain trait evolution, but which of these outcomes predominates remains uncertain. Here, we develop tools for fitting phylogenetic models of phenotypic evolution in which the impact of species interactions—namely, competition—can vary across lineages. Deploying these models on a global avian trait dataset to explore differences in trait divergence between tropical and temperate lineages, we find that the effect of latitude on the mode and tempo of morphological evolution is weak and clade- or trait dependent. Our results indicate that species interactions do not disproportionately impact morphological evolution in tropical bird families and question the validity of previously reported patterns of slower trait evolution in the tropics.

Analyses of morphological measurements from over 9400 bird species reveal that interactions between species have impacted evolution, but fail to support the longstanding hypothesis that competition is stronger in the tropics.     

Accommodation of tmRNA–SmpB into stalled ribosomes: A cryo-EM study

In eubacteria, translation of defective messenger RNAs (mRNAs) produces truncated polypeptides that stall on the ribosome. A quality control mechanism referred to as trans-translation is performed by transfer-messenger RNA (tmRNA), a specialized RNA acting as both a tRNA and an mRNA, associated with small protein B (SmpB). So far, a clear view of the structural movements of both the protein and RNA necessary to perform accommodation is still lacking. By using a construct containing the tRNA-like domain as well as the extended helix H2 of tmRNA, we present a cryo-electron microscopy study of the process of accommodation. The structure suggests how tmRNA and SmpB move into the ribosome decoding site after the release of EF-Tu·GDP. While two SmpB molecules are bound per ribosome in a preaccommodated state, our results show that during accommodation the SmpB protein interacting with the small subunit decoding site stays in place while the one interacting with the large subunit moves away. Relative to canonical translation, an additional movement is observed due to the rotation of H2. This suggests that the larger movement required to resume translation on a tmRNA internal open reading frame starts during accommodation.     

Chemoenzymatic routes to enantiomerically pure 2-azatyrosine and 2-, 3- and 4-pyridylalanine derivatives

Enantiomerically pure 2-, 3- or 4-pyridylalanine (pya) and 2-azatyrosine (azatyr) are known to present various biological activities. After incorporation into appropriate peptide sequences, these heterocyclic non natural α-amino acids could behave as new substrates or inhibitors of elastase from Pseudomonas aeruginosa. This enzyme is known to be involved in nosocomial infections and infections related to the cystic fibrosis disease. New efficient chemoenzymatic preparations of those compounds using α-chymotrypsin (α-CT) are presented.     

The hydrophobic proteome of mitochondrial membranes from Arabidopsis cell suspensions

The development of mitochondria and the integration of their function within a plant cell rely on the presence of a complex biochemical machinery located within their limiting membranes. The aim of the present work was: (1) to enhance our understanding of the biochemical machinery of mitochondrial membranes and (2) to test the versatility of the procedure developed for the identification of the hydrophobic proteome of the chloroplast envelope [Molecular and Cellular Proteomics 2 (2003) 325-345]. A proteomic analysis was performed, to provide the most exhaustive view of the protein repertoire of these membranes. For this purpose, highly purified mitochondria were prepared from Arabidopsis cultured cells and membrane proteins were extracted. To get a more exhaustive array of membrane proteins from Arabidopsis mitochondria, from the most to the less hydrophobic ones, various extraction procedures (chloroform/methanol extraction, alkaline or saline treatments) were applied. LC-MS/MS analyses were then performed on each membrane subfraction, leading to the identification of more than 110 proteins. The identification of these proteins is discussed with respect to their mitochondrial localization, their physicochemical properties and their implications in the metabolism of mitochondria. In order to provide a new overview of the biochemical machinery of the plant mitochondria, proteins identified during this work were compared to the lists of proteins identified during previous proteomic analyses performed on plant and algae mitochondria (Arabidopsis, pea, Chlamydomonas, rice, etc.). A total of 502 proteins are listed. About 40% of the 114 proteins identified during this work were not identified during previous proteomic studies performed on mitochondria.     

Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial

We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.     

Climatic drivers of pinyon mouse Peromyscus truei population dynamics in a resource-restricted environment

Highly variable patterns in temperature and rainfall events can have pronounced consequences for small mammals in resource-restricted environments. Climatic factors can therefore play a crucial role in determining the fates of small mammal populations. We applied Pradel's temporal symmetry model to a 21-year capture–recapture dataset to study population dynamics of the pinyon mouse (Peromyscus truei) in a semi-arid mixed oak woodland in California, USA. We examined time-, season- and sex-specific variation in realized population growth rate (λ) and its constituent vital rates, apparent survival and recruitment. We also tested the influence of climatic factors on these rates. Overall monthly apparent survival was 0.81 ± 0.004 (estimate ± SE). Survival was generally higher during wetter months (October–May) but varied over time. Monthly recruitment rate was 0.18 ± 0.01, ranging from 0.07 ± 0.01 to 0.63 ± 0.07. Although population growth rate (λ) was highly variable, overall monthly growth rate was close to 1.0, indicating a stable population during the study period (λ ± SE = 0.99 ± 0.01). Average temperature and its variability negatively affected survival, whereas rainfall positively influenced survival and recruitment rates, and thus the population growth rate. Our results suggest that seasonal rainfall and variation in temperature at the local scale, rather than regional climatic patterns, more strongly affected vital rates in this population. Discerning such linkages between species' population dynamics and environmental variability are critical for understanding local and regional impacts of global climate change, and for gauging viability and resilience of populations in resource-restricted environments.