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Effective population size (Ne) is a pivotal evolutionary parameter with crucial implications in conservation practice and policy. Genetic methods to estimate Ne have been preferred over demographic methods because they rely on genetic data rather than time‐consuming ecological monitoring. Methods based on linkage disequilibrium (LD), in particular, have become popular in conservation as they require a single sampling and provide estimates that refer to recent generations. A software program based on the LD method, GONE, looks particularly promising to estimate contemporary and recent‐historical Ne (up to 200 generations in the past). Genomic datasets from non‐model species, especially plants, may present some constraints to the use of GONE, as linkage maps and reference genomes are seldom available, and SNP genotyping is usually based on reduced‐representation methods. In this study, we use empirical datasets from four plant species to explore the limitations of plant genomic datasets when estimating Ne using the algorithm implemented in GONE, in addition to exploring some typical biological limitations that may affect Ne estimation using the LD method, such as the occurrence of population structure. We show how accuracy and precision of Ne estimates potentially change with the following factors: occurrence of missing data, limited number of SNPs/individuals sampled, and lack of information about the location of SNPs on chromosomes, with the latter producing a significant bias, previously unexplored with empirical data. We finally compare the Ne estimates obtained with GONE for the last generations with the contemporary Ne estimates obtained with the programs currentNe and NeEstimator. [ABSTRACT FROM AUTHOR]

Background: The American Bashkir Curly Horse is frequently advertised to horse‐allergic riders and claimed to be a so‐called hypoallergenic breed that elicits fewer symptoms. Previous studies quantifying selected allergens in different breeds did not find a reduced allergen content in Curly Horses. Here, we provide a comprehensive proteomic analysis of horse hair extracts and a molecular analysis of the major allergen Equ c 1 with the aim of identifying differences in the Curly Horse breed that might explain their presumed reduced allergenic potential. Methods: Horse hair extracts were prepared from Curly and American Quarter Horse breeds, separated by gender and castration status, extracts from other breeds served as controls. Extracts and native Equ c 1 (nEqu c 1) were analyzed by mass spectrometry. IgE‐binding capacities of nEqu c 1 and its recombinant variants were tested by ELISA using sera of patients sensitized to horses. Structures and ligand binding abilities were analyzed by computational modeling and fluorescence quenching assays. Results: All known respiratory horse allergens are present in hair extracts of Curly and Quarter Horses and share identical allergen‐specific peptides. Lipocalin allergens are the most abundant proteins in horse hair extracts and contain several post‐translational modifications. We identified two new variants of Equ c 1 that have similar IgE‐binding capacities but show structural differences in their binding cavities and altered ligand binding behavior. There are no differences in IgE‐binding of Equ c 1 derived from Curly Horses compared to other horse breeds. Conclusion: Our data do not support the claim that Curly Horses are less allergenic than other breeds. [ABSTRACT FROM AUTHOR]

Next‐generation biomonitoring proposes to combine machine‐learning algorithms with environmental DNA data to automate the monitoring of the Earth's major ecosystems. In the present study, we searched for molecular biomarkers of tree water status to develop next‐generation biomonitoring of forest ecosystems. Because phyllosphere microbial communities respond to both tree physiology and climate change, we investigated whether environmental DNA data from tree phyllosphere could be used as molecular biomarkers of tree water status in forest ecosystems. Using an amplicon sequencing approach, we analysed phyllosphere microbial communities of four tree species (Quercus ilex, Quercus robur, Pinus pinaster and Betula pendula) in a forest experiment composed of irrigated and non‐irrigated plots. We used these microbial community data to train a machine‐learning algorithm (Random Forest) to classify irrigated and non‐irrigated trees. The Random Forest algorithm detected tree water status from phyllosphere microbial community composition with more than 90% accuracy for oak species, and more than 75% for pine and birch. Phyllosphere fungal communities were more informative than phyllosphere bacterial communities in all tree species. Seven fungal amplicon sequence variants were identified as candidates for the development of molecular biomarkers of water status in oak trees. Altogether, our results show that microbial community data from tree phyllosphere provides information on tree water status in forest ecosystems and could be included in next‐generation biomonitoring programmes that would use in situ, real‐time sequencing of environmental DNA to help monitor the health of European temperate forest ecosystems. [ABSTRACT FROM AUTHOR]

The synthesis of four clickable sydnone‐heptamethine cyanine derivatives is described in this article. The synthetic route is based on a palladium‐cross coupling reactions of sydnone boronates affording the desired sydnone‐cyanine conjugates in only five steps. These compounds were shown to react smoothly with cyclooctynes to form the corresponding pyrazoles clicked products quantitatively at room temperature and with rate constants up to 18 m−1 ⋅ s−1, affording interesting new tools for biorthogonal fluorescent labelling of (bio)molecules. Fluorescence properties of both sydnone‐ and pyrazole‐cyanines are described, as well. [ABSTRACT FROM AUTHOR]

Microgeographical adaptation occurs when the effects of directional selection persist despite gene flow. Traits and genetic loci under selection can then show adaptive divergence, against the backdrop of little differentiation at other traits or loci. How common such events are and how strong the selection is that underlies them remain open questions. Here, we discovered and analysed microgeographical patterns of genomic divergence in four European and Mediterranean conifers with widely differing life‐history traits and ecological requirements (Abies alba MIll., Cedrus atlantica [Endl.] Manetti, Pinus halepensis Mill. and Pinus pinaster Aiton) by screening pairs from geographically close forest stands sampled along steep ecological gradients. We inferred patterns of genomic divergence by applying a combination of divergence outlier detection methods, demographic modelling, Approximate Bayesian Computation inferences and genomic annotation to genomic data. Surprisingly for such small geographical scales, we showed that selection is strong in all species but generally affects different loci in each. A clear signature of selection was systematically detected on a fraction of the genome, of the order of 0.1%–1% of the loci depending on the species. The novel modelling method we designed for estimating selection coefficients showed that the microgeographical selection coefficient scaled by population size (Ns) was 2–30. Our results convincingly suggest that selection maintains within‐population diversity at microgeographical scales in spatially heterogeneous environments. Such genetic diversity is likely to be a major reservoir of adaptive potential, helping populations to adapt under fluctuating environmental conditions. [ABSTRACT FROM AUTHOR]

Orthogonal chemistry is a valuable tool in the preparation of complex molecules as heteroglycoclusters. Unfortunately, selective heteroconjugation of multifunctional starting materials remains a usually challenging problem to overcome. Herein, we report the first report on harnessing N‐alkylation of N‐acylhydrazone as a key step in the orthogonal synthesis. Sequentially associated with the azido‐alkyne click chemistry, it stands out as a new and straightforward synthetic method of glycoconjugate small molecules, heterodisaccharides, and heteroglycoclusters based on cone p‐tBu‐calix[4]arene and 1,3‐alt p‐tBu‐thiacalix[4]arene with potential drug‐like properties. [ABSTRACT FROM AUTHOR]

High genetic variation and extensive gene flow may help forest trees with adapting to ongoing climate change, yet the genetic bases underlying their adaptive potential remain largely unknown. We investigated range‐wide patterns of potentially adaptive genetic variation in 64 populations of European beech (Fagus sylvatica L.) using 270 SNPs from 139 candidate genes involved either in phenology or in stress responses. We inferred neutral genetic structure and processes (drift and gene flow) and performed differentiation outlier analyses and gene‐environment association (GEA) analyses to detect signatures of divergent selection. Beech range‐wide genetic structure was consistent with the species' previously identified postglacial expansion scenario and recolonization routes. Populations showed high diversity and low differentiation along the major expansion routes. A total of 52 loci were found to be putatively under selection and 15 of them turned up in multiple GEA analyses. Temperature and precipitation related variables were equally represented in significant genotype‐climate associations. Signatures of divergent selection were detected in the same proportion for stress response and phenology‐related genes. The range‐wide adaptive genetic structure of beech appears highly integrated, suggesting a balanced contribution of phenology and stress‐related genes to local adaptation, and of temperature and precipitation regimes to genetic clines. Our results imply a best‐case scenario for the maintenance of high genetic diversity during range shifts in beech (and putatively other forest trees) with a combination of gene flow maintaining within‐population neutral diversity and selection maintaining between‐population adaptive differentiation. [ABSTRACT FROM AUTHOR]

Identification of a common Diels–Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ‐unsaturated lactams. A practical and readily scalable route to the parent p‐methoxybenzyl‐protected 6‐ and 7‐membered β,γ‐unsaturated lactams was developed. These were readily transformed into the corresponding O‐silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts. These exhibited unexpected and versatile transformations upon acid hydrolysis depending on the nature of the dienophile substituents and the acid catalyst. All reactions have been performed on multigram quantities. These transformations provide a convenient, economical, and easily scalable pathway for the rapid construction of functionally and stereochemically dense privileged scaffolds for the construction of libraries of natural products‐inspired molecules of pharmacological relevance. [ABSTRACT FROM AUTHOR]

Most existing forests are subjected to natural and human‐mediated selection pressures, which have increased due to climate change and the increasing needs of human societies for wood, fibre and fuel resources. It remains largely unknown how these pressures trigger evolutionary changes. We address this issue here for temperate European oaks (Quercus petraea and Q. robur), which grow in mixed stands, under even‐aged management regimes. We screened numerous functional traits for univariate selection gradients and for expected and observed genetic changes over two successive generations. In both species, growth, leaf morphology and physiology, and defence‐related traits displayed significant selection gradients and predicted shifts, whereas phenology, water metabolism, structure and resilience‐related traits did not. However, the direction of the selection response and the potential for adaptive evolution differed between the two species. Quercus petraea had a much larger phenotypic and genetic variance of fitness than Q. robur. This difference raises concerns about the adaptive response of Q. robur to contemporary selection pressures. Our investigations suggest that Q. robur will probably decline steadily, particularly in mixed stands with Q. petraea, consistent with the contrasting demographic dynamics of the two species. [ABSTRACT FROM AUTHOR]

Summary: The tree of life is highly reticulate, with the history of population divergence emerging from populations of gene phylogenies that reflect histories of introgression, lineage sorting and divergence. In this study, we investigate global patterns of oak diversity and test the hypothesis that there are regions of the oak genome that are broadly informative about phylogeny.We utilize fossil data and restriction‐site associated DNA sequencing (RAD‐seq) for 632 individuals representing nearly 250 Quercus species to infer a time‐calibrated phylogeny of the world's oaks. We use a reversible‐jump Markov chain Monte Carlo method to reconstruct shifts in lineage diversification rates, accounting for among‐clade sampling biases. We then map the > 20 000 RAD‐seq loci back to an annotated oak genome and investigate genomic distribution of introgression and phylogenetic support across the phylogeny.Oak lineages have diversified among geographic regions, followed by ecological divergence within regions, in the Americas and Eurasia. Roughly 60% of oak diversity traces back to four clades that experienced increases in net diversification, probably in response to climatic transitions or ecological opportunity.The strong support for the phylogeny contrasts with high genomic heterogeneity in phylogenetic signal and introgression. Oaks are phylogenomic mosaics, and their diversity may in fact depend on the gene flow that shapes the oak genome. See also the Editorial on this article by Plomion & Martin, 226: 943–946. [ABSTRACT FROM AUTHOR]

The apelinergic pathway has been generating increasing interest in the past few years for its potential as a therapeutic target in several conditions associated with the cardiovascular and metabolic systems. Indeed, preclinical and, more recently, clinical evidence both point to this G protein–coupled receptor as a target of interest in the treatment of not only cardiovascular disorders such as heart failure, pulmonary arterial hypertension, atherosclerosis, or septic shock, but also of additional conditions such as water retention/hyponatremic disorders, type 2 diabetes, and preeclampsia. While it is a peculiar system with its two classes of endogenous ligand, the apelins and Elabela, its intricacies are a matter of continuing investigation to finely pinpoint its potential and how it enables crosstalk between the vasculature and organ systems of interest. In this perspective article, we first review the current knowledge on the role of the apelinergic pathway in the above systems, as well as the associated therapeutic indications and existing pharmacological tools. We also offer a perspective on the challenges and potential ahead to advance the apelinergic system as a target for therapeutic intervention in several key areas. [ABSTRACT FROM AUTHOR]

Abstract: We propose a reduced dynamical system describing the coupled evolution of fluid flow and magnetic field at the top of the Earth's core between the years 1900 and 2014. The flow evolution is modeled with a first‐order autoregressive process, while the magnetic field obeys the classical frozen flux equation. An ensemble Kalman filter algorithm serves to constrain the dynamics with the geomagnetic field and its secular variation given by the COV‐OBS.x1 model. Using a large ensemble with 40,000 members provides meaningful statistics including reliable error estimates. The model highlights two distinct flow scales. Slowly varying large‐scale elements include the already documented eccentric gyre. Localized short‐lived structures include distinctly ageostophic features like the high‐latitude polar jet on the Northern Hemisphere. Comparisons with independent observations of the length‐of‐day variations not only validate the flow estimates but also suggest an acceleration of the geostrophic flows over the last century. Hindcasting tests show that our model outperforms simpler predictions bases (linear extrapolation and stationary flow). The predictability limit, of about 2,000 years for the magnetic dipole component, is mostly determined by the random fast varying dynamics of the flow and much less by the geomagnetic data quality or lack of small‐scale information. [ABSTRACT FROM AUTHOR]

Mars is believed to have possessed a dynamo that ceased operating approximately 4 Ga ago, although the exact time is still under debate. The scope of this study is to constrain the possible timing of its cessation by studying the magnetization signatures of craters. The study uses the latest available model of the lithospheric magnetic field of Mars, which is based on Mars Global Surveyor data. We tackle the problem of nonuniqueness that characterizes the inversion of magnetic field data for the magnetization by inferring only the visible part of the magnetization, that is, the part of the magnetization that gives rise to the observed magnetic field. Further on, we demonstrate that a zero visible magnetization is a valid proxy for the entire magnetization being zero under the assumption of a magnetization distribution of induced geometry. This assumption holds for craters whose thermoremanent magnetization has not been significantly altered since its acquisition. Our results show that the dynamo shut off after the impacts that created the Acidalia and SE Elysium basins and before the crust within the Utopia basin cooled below its magnetic blocking temperature. Accounting for the age uncertainties in the dating of these craters, we estimate that the dynamo shut off at an N(300) crater retention age of 2.5-3.2 or an absolute model age of 4.12-4.14 Ga. Moreover, the Martian dynamo may have been weaker in its early stage, which if true implies that the driving mechanism of the Martian dynamo was not the same throughout its history. [ABSTRACT FROM AUTHOR]

Testing how populations are locally adapted and predicting their response to their future environment is of key importance in view of climate change. Landscape genomics is a powerful approach to investigate genes and environmental factors involved in local adaptation. In a pooled amplicon sequencing approach of 94 genes in 71 populations, we tested whether >3500 single nucleotide polymorphisms ( SNPs) in the three most common oak species in Switzerland ( Quercus petraea, Q. pubescens, Q. robur) show an association with abiotic factors related to local topography, historical climate and soil characteristics. In the analysis including all species, the most frequently associated environmental factors were those best describing the habitats of the species. In the species-specific analyses, the most important environmental factors and associated SNPs greatly differed among species. However, we identified one SNP and seven genes that were associated with the same environmental factor across all species. We finally used regressions of allele frequencies of the most strongly associated SNPs along environmental gradients to predict the risk of nonadaptedness ( RONA), which represents the average change in allele frequency at climate-associated loci theoretically required to match future climatic conditions. RONA is considerable for some populations and species (up to 48% in single populations) and strongly differs among species. Given the long generation time of oaks, some of the required allele frequency changes might not be realistic to achieve based on standing genetic variation. Hence, future adaptedness requires gene flow or planting of individuals carrying beneficial alleles from habitats currently matching future climatic conditions. [ABSTRACT FROM AUTHOR]

Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism ( SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred ( F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies. [ABSTRACT FROM AUTHOR]

Miscanthus × giganteus is often regarded as one of the most promising crops to produce bioenergy because it is renowned for its high biomass yields, combined with low input requirements. However, its productivity has been mainly studied in experimental conditions. Our study aimed at characterizing and explaining young M. giganteus yield variability on a farmers' field network located in the supply area of a cooperative society in east central France. It included the first three growth years of the crop. We defined and calculated a set of indicators of limiting factors that could be involved in yield variations and used the mixed-model method to identify those explaining most of the yield variation. Commercial yields averaged 8.1 and 12.8 t DM ha−1 for the second and third growth year, respectively. However, these mean results concealed a high variability, ranging from 3 to 19 t DM ha−1. Commercial yields, measured on whole fields, were on average 20% lower than plot yields, measured on a small area (two plots of 25 m2). Yields were found to be much more related to shoot density than to shoot mass, and particularly to the shoot density established at the end of the planting year. We highlighted that planting success was decisive and was built during the whole plantation year. Fields with the lowest yields also had the highest weed cover, which was influenced by the distance between the field and the farmhouse, the preceding crop and the soil type. Our findings show that growing young M. giganteus on farmers' fields involves limiting factors different from those commonly reported in the literature for experimental conditions and they could be useful to assess the economic and environmental impacts of growing M. giganteus on farmers' fields. They could also stimulate the discussion about growing bioenergy crops on marginal lands. [ABSTRACT FROM AUTHOR]

An Illumina Infinium SNP genotyping array was constructed for European white oaks. Six individuals of Quercus petraea and Q. robur were considered for SNP discovery using both previously obtained Sanger sequences across 676 gene regions (1371 in vitro SNPs) and Roche 454 technology sequences from 5112 contigs (6542 putative in silico SNPs). The 7913 SNPs were genotyped across the six parental individuals, full-sib progenies (one within each species and two interspecific crosses between Q. petraea and Q. robur) and three natural populations from south-western France that included two additional interfertile white oak species ( Q. pubescens and Q. pyrenaica). The genotyping success rate in mapping populations was 80.4% overall and 72.4% for polymorphic SNPs. In natural populations, these figures were lower (54.8% and 51.9%, respectively). Illumina genotype clusters with compression (shift of clusters on the normalized x-axis) were detected in ~25% of the successfully genotyped SNPs and may be due to the presence of paralogues. Compressed clusters were significantly more frequent for SNPs showing a priori incorrect Illumina genotypes, suggesting that they should be considered with caution or discarded. Altogether, these results show a high experimental error rate for the Infinium array (between 15% and 20% of SNPs potentially unreliable and 10% when excluding all compressed clusters), and recommendations are proposed when applying this type of high-throughput technique. Finally, results on diversity levels and shared polymorphisms across targeted white oaks and more distant species of the Quercus genus are discussed, and perspectives for future comparative studies are proposed. [ABSTRACT FROM AUTHOR]

Systematic sequencing is the method of choice for generating genomic resources for molecular marker development and candidate gene identification in nonmodel species. We generated 47 357 Sanger ESTs and 2.2M Roche-454 reads from five cDNA libraries for European beech ( Fagus sylvatica L.). This tree species of high ecological and economic value in Europe is among the most representative trees of deciduous broadleaf forests. The sequences generated were assembled into 21 057 contigs with MIRA software. Functional annotations were obtained for 85% of these contigs, from the proteomes of four plant species, Swissprot accessions and the Gene Ontology database. We were able to identify 28 079 in silico SNPs for future marker development. Moreover, RNAseq and qPCR approaches identified genes and gene networks regulated differentially between two critical phenological stages preceding vegetative bud burst (the quiescent and swelling buds stages). According to climatic model-based projection, some European beech populations may be endangered, particularly at the southern and eastern edges of the European distribution range, which are strongly affected by current climate change. This first genomic resource for the genus Fagus should facilitate the identification of key genes for beech adaptation and management strategies for preserving beech adaptability. [ABSTRACT FROM AUTHOR]

Introduction Hairy root cultures of Linum sp. are an alternative for the high production of lignans. Linum perenne is known to produce arylnaphthalene-type lignans such as justicidin B, isojusticidin and diphyllin. Objective To elucidate the presence of aryltetralin-type lignan diastereoisomers, besides the known arylnaphthalene-type lignans, in hairy roots of Linum perenne, and to determine the configurations of one diastereoisomer of 6-methoxypodophyllotoxin (6-MPTOX). Methods Lignans from hairy root cultures of Linum perenne were extracted and separated by HPLC. Arylnaphthalene-type lignans were identified by LC-MS, according to the literature. Two diastereoisomers of aryltetralin-type lignans were analysed by mass spectrometry and NMR spectroscopy. Results Numerous arylnaphthalene-type lignans (diphyllin-2-hexose-pentose, diphyllin-3-pentose and diphyllin-hexose) were identified in hairy root cultures. Methoxypodophyllotoxin, an aryltetralin-type lignan, was also identified, as well as one diastereoisomer. This aryltetralin-type lignan could be derived via 7-hydroxymatairesinol as a hypothetical biosynthetic pathway. The stereochemical configurations of aryltetralin isomers were determined. Conclusion Arylnaphthalene and two diastereoisomers of aryltetralin-type lignans are produced in Linum perenne hairy root cultures. Matairesinol, the precursor of justicidin B, also seems to be converted into 6-MPTOX via 7-hydroxymatairesinol. This is the first report of the stereochemical configurations of an aryltetralin-type lignan other than podophyllotoxin (PTOX). Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The clinical benefits of oseltamivir (Tamiflu) are well established, but the effects of antiviral treatment on the immune response are poorly understood. By use of flow cytometric analyses and the mouse model, we thoroughly investigated the impact of such a treatment on the immune response and the generation of protective immunity to influenza. We demonstrated that influenzaspecific CD8+ effector T cell recruitment was reduced up to 81% in the lungs of mice treated with oseltamivir (5 or 50 mg/kg twice daily; EC50 49 nM in vitro) compared to saline controls, but cell generation was unaffected in draining lymph nodes. Importantly, we showed that oseltamivir administration significantly decreased the pools of tissue-resident and circulating effector memory (93.7%) and central memory CD8+ Tcells (45%) compared to saline controls. During heterologous secondary infection, a decreased memory CD8+ T cell pool combined with reduced generation of secondary influenza-specific effectors in the lymph nodes resulted in 10-fold decreased CD8+ T cell recall responses, which increased mouse morbidity and delayed viral clearance. Furthermore, antiviral administration led to a significant 5.7-fold decreased production of functional anti-influenza antibodies. Thus, our study demonstrates that antiviral treatment affects the development of the adaptive immune response and protective immunity against influenza. [ABSTRACT FROM AUTHOR]

Miscanthus × giganteus is often regarded as one of the most promising crops to produce sustainable bioenergy. This perennial crop, renowned for its high productivity associated with low input requirements, in particular regarding fertilizers, is thought to have low environmental impacts, but few data are available to confirm this. Our study aimed at assessing nitrate leaching from Miscanthus × giganteus crops in farmers' fields, thus including a wide range of soil and cropping system conditions. We focused on the first years of growth after planting as experimental studies have suggested that Miscanthus × giganteus, once established, results in low nitrate leaching. We combined on-farm measurements and modeling to estimate drainage, leached nitrogen, and nitrate concentration in drainage water in 38 fields located in Center-East France during two winters (November 2010 to March 2011, November 2011 to March 2012). Nitrate leaching and nitrate concentration in drainage water were on average very low. Nitrate leaching averaged 6 kg N ha−1 whereas nitrate concentration averaged 12 mg l−1. These low values are attributable to the low estimates of drainage water (mean = 166 mm) but also to the low soil mineral nitrogen contents measured at the beginning of winter (mean = 37 kg N ha−1). Our results were, however, very variable, mainly due to the crop age: nitrate leaching and nitrate concentration were critically higher during the winter following the first growth year of Miscanthus × giganteus, reflecting the low development of the crop. This variability was also explained by the range of soil and cropping conditions explored in the on-farm design: shallow and/or sandy soils as well as fields where establishment failed had a higher risk of nitrate leaching. [ABSTRACT FROM AUTHOR]

Maritime pine ( Pinus pinaster Ait.) is a widely distributed conifer species in Southwestern Europe and one of the most advanced models for conifer research. In the current work, comprehensive characterization of the maritime pine transcriptome was performed using a combination of two different next-generation sequencing platforms, 454 and Illumina. De novo assembly of the transcriptome provided a catalogue of 26 020 unique transcripts in maritime pine trees and a collection of 9641 full-length c DNAs. Quality of the transcriptome assembly was validated by RT- PCR amplification of selected transcripts for structural and regulatory genes. Transcription factors and enzyme-encoding transcripts were annotated. Furthermore, the available sequencing data permitted the identification of polymorphisms and the establishment of robust single nucleotide polymorphism ( SNP) and simple-sequence repeat ( SSR) databases for genotyping applications and integration of translational genomics in maritime pine breeding programmes. All our data are freely available at Sustainpine DB, the P. pinaster expressional database. Results reported here on the maritime pine transcriptome represent a valuable resource for future basic and applied studies on this ecological and economically important pine species. [ABSTRACT FROM AUTHOR]

Afin de montrer l'importance de la réglementation et de la productivité naturelle dans la valorisation des surfaces de production ostréicoles, nous avons estimé une fonction de prix hédonique des concessions ostréicoles arcachonnaises. Les « terres ostréicoles » ont comme particularité d'être des concessions du Domaine Public Maritime et sont à ce titre soumises à son régime protecteur. Néanmoins, loin d'entraver l'activité ostréicole par les contraintes qu'elle impose, la réglementation se révèle être une garante du maintien d'un niveau satisfaisant de productivité naturelle des concessions pour permettre une reproduction et une croissance des huîtres dans des conditions favorables. Ainsi, les résultats de la modélisation montrent que plus de la moitié du prix d'échange des concessions est déterminé par les conditions réglementaires régissant leur utilisation. Ils soulignent également que les conditions du milieu ne sont pas identiques sur l'ensemble du Bassin d'Arcachon justifiant une réglementation adaptée aux différences de productivité naturelle. [ABSTRACT FROM AUTHOR]

In search of a next generation molecule to the novel wake-promoting agent modafinil, a series of aryl-heteroayl-derived wakefulness enhancing agents (in rats) was developed. From this work, compound 16 was separated into its enantiomers to profile them individually. [ABSTRACT FROM AUTHOR]

In the presence of inflammation, iron availability for erythropoiesis is decreased, and hemoglobin production is reduced in reticulocytes. The reticulocyte hemoglobin content (CHr) provides a real picture of bone marrow status and could be useful to evaluate iron metabolism in critically ill patients. We conducted a preliminary study to evaluate the feasibility to measure the CHr in the intensive care units of two university hospitals and to evaluate the impact of C-reactive protein on CHr values. The CHr was measured in 14 consecutive critically ill patients hospitalized in the intensive care unit between 48 and 96 hours. One patient with a ferritin concentration < 100 µg/L was excluded to eliminate a possible coexistence of iron deficiency with inflammation. A statistically significant correlation was observed between C-reactive protein concentrations and CHr values ( r = −0.588; P = 0.03, n = 13). The results observed in this preliminary study are interesting and could be useful to establish the research protocol for a future study evaluating iron metabolism in critically ill patients. A larger study is feasible and warranted given the results observed in this preliminary study. [ABSTRACT FROM AUTHOR]

Sugars modulate many vital metabolic and developmental processes in plants, from seed germination to flowering, senescence and protection against diverse abiotic and biotic stresses. However, the exact mechanisms involved in morphogenesis, developmental signalling and stress tolerance remain largely unknown. Here we report the characterization of a novel Arabidopsis thaliana mutant, sweetie, with drastically altered morphogenesis, and a strongly modified carbohydrate metabolism leading to elevated levels of trehalose, trehalose-6-phosphate and starch. We additionally show that the disruption of SWEETIE causes significant growth and developmental alterations, such as severe dwarfism, lancet-shaped leaves, early senescence and flower sterility. Genes implicated in sugar metabolism, senescence, ethylene biosynthesis and abiotic stress were found to be upregulated in sweetie. Our physiological, biochemical, genetic and molecular data indicate that the mutation in sweetie was nuclear, single and recessive. The effects of metabolizable sugars and osmolytes on sweetie morphogenesis were distinct; in light, sweetie was hypersensitive to sucrose and glucose during vegetative growth and a partial phenotypic reversion took place in the presence of high sorbitol concentrations. However, SWEETIE encodes a protein that is unrelated to any known enzyme involved in sugar metabolism. We suggest that SWEETIE plays an important regulatory function that influences multiple metabolic, hormonal and stress-related pathways, leading to altered gene expression and pronounced changes in the accumulation of sugar, starch and ethylene. [ABSTRACT FROM AUTHOR]

Abstract: Triggering receptor expressed on myeloid cell-1 (TREM-1) is a recently described receptor that has many effects on polymorphonuclear neutrophil (PMN), as the engagement of this receptor on PMN can induce phagocytosis, respiratory burst and degranulation. We studied the effects of aging on TREM-1 engagement in human PMN. PMN from elderly were found to have impaired response following TREM-1 engagement. Notably they were not able to modulate the TREM-1-induced respiratory burst as PMN from young did. TREM-1 engagement could not reverse PMN survival following incubation with LPS or GM-CSF in the elderly whereas it did in the young. The phosphorylation of TREM-1 signal transduction molecules was altered with aging. Finally, TREM-1 engagement could not drive the recruitment of TREM-1 in the lipid-rafts of the elderly explaining in part the altered response. The observed alterations in TREM-1 response are possibly an important contributing factor in the higher incidence of sepsis-related deaths in the elderly population. [Copyright &y& Elsevier]

To study the effects of a matrix metalloproteinase (MMP) inhibitor (S‐34219) on osteoarthritis (OA) cartilage cultures and in the meniscectomized guinea pig model of OA.The inhibitory activity of S‐34219 on MMPs and aggrecanase was studied by fluorimetry and immunoassay, respectively. The effects of S‐34219 on proteoglycan and collagen degradation were studied in cultures of rabbit and human cartilage. Medial meniscectomy was performed on 29 Hartley male guinea pigs, and these animals were randomly allocated to 1 of 3 groups: a control meniscectomized group (MNXc) receiving the vehicle, or a meniscectomized group receiving either 10 mg/kg or 20 mg/kg S‐34219, administered twice per day by oral gavage for 12 weeks from day 1 after surgery. An additional group comprised sham‐operated animals. Tibial cartilage from the operated left knee was processed for histologic assessment of OA lesions.The 50% inhibitory concentration (IC50) of S‐34219 on MMPs 1, 2, 3, 8, 9, and 13 was 55, 0.1, 0.5, 0.1, 0.03, and 0.2 nM, respectively; the IC50 on aggrecanase 1 was 190 nM. In cultured rabbit cartilage, 100 nM S‐34219 strongly inhibited MMP‐dependent degradation of collagen and proteoglycans. A concentration 100 times higher was needed to inhibit aggrecanase‐dependent degradation. In cultures of human OA cartilage, 100 nM S‐34219 inhibited spontaneous type II collagen degradation by 66% and proteoglycan degradation by only 22%. For in vivo studies, treated groups were compared with the MNXc group and the results, expressed as the percentage variation versus MNXc, were as follows: in the 10 and 20 mg/kg groups, a significant decrease (P < 0.05) in global histologic score (−12% and −14%, respectively) was observed, and this was associated with a significant increase (P < 0.05) in cartilage thickness (+19% and +18%, respectively). Neither dose level changed the proteoglycan content.In both treated animal groups, S‐34219 significantly prevented the loss of cartilage thickness, probably by inhibiting collagen breakdown that normally leads to the erosion of fibrillated superficial areas. The absence of a protective effect on glycosaminoglycan loss, both in vitro and in vivo, suggests that aggrecanases may have an important role in cartilage loss. This study reinforces the relevance of these models for testing chondroprotective drugs, and the potential role of dual inhibitors of collagenase and aggrecanase as disease‐modifying drugs in the management of OA. [ABSTRACT FROM AUTHOR]

It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age. [ABSTRACT FROM AUTHOR]

The apelinergic system emerges as an important regulator of cardiovascular functions via its actions on the heart, vasculature, and kidney. It also possesses additional beneficial properties, via its actions on the pancreas and skeletal muscle, on type 2 diabetes. The apelinergic system distinguishes itself by the presence of two structurally distinct sets of endogenous ligands, the Apelins (–13, −17, and −36) and Elabela, which both activate the apelin (APJ) receptor. In the past decade, numerous peptidic ligands have been used to better understand the structure–activity relationship of apelin (and more recently Elabela), providing important tools to rationalize how ligand modifications impact receptor structure and dynamics as well as its downstream signaling. The recently disclosed structure of the apelin receptor in complex with an analogue of apelin‐17 provides an important tool in this quest. In this review, we first summarize the physiopharmacology of the apelinergic system, then, review existing knowledge on the various ligands of the apelin receptor with an emphasis on peptidic ligands, although small molecules are covered as well. Throughout this work, we tried to integrate existing knowledge of ligands' pharmacological profiles with structure and signaling profile. [ABSTRACT FROM AUTHOR]

Rock magnetization carries information about rocks' properties, Earth's tectonic history, and evolution of its core magnetic field. One way to study Earth's magnetization is through the magnetic signal it generates, known as the lithospheric magnetic field. Although there exist global lithospheric magnetic field models of high spatial resolution, this path has not yet been very fruitful because of an important limitation: only part of the magnetization is visible, that is, produces an observable magnetic field signal. We refer to the remaining part of the magnetization as the hidden magnetization, and we recover it from a lithospheric magnetic field model under a few reasonable assumptions. We find that Earth's hidden magnetization at high and middle latitudes is very similar, both in intensity and shape, to Earth's visible magnetization. At low latitudes, the estimated hidden magnetization relies on a priori information and can be very different from the visible one. Plain Language Summary: Earth's uppermost layer is abundant in magnetized rocks. Rocks' magnetization acts as a recorder of many processes taking place inside the Earth, from the crust down to the core, which lies almost 3,000 km far from the surface. Currently, the most common way to extract this information is through laboratory measurements of rock samples. An alternative way is to study the magnetic signal of magnetized rocks, which is known as the lithospheric magnetic field. This is measured by satellites orbiting around the Earth and airborne and marine missions. Inferring, however, the direction and the strength of the magnetization from magnetic field measurements is not straightforward. The reason is that a large part of a given magnetization generates no magnetic field. We call this part of the magnetization hidden as opposed to the remaining part, which we call visible. In this study, we show how the visible and the hidden parts of the magnetization are linked to each other. This link allows us to uniquely recover most of Earth's hidden magnetization. Recovering this part of Earth's magnetization enables a better link to the underlying processes, like crustal thickness contrasts, temperature gradients, hydrothermal activity, or deposits of highly magnetic minerals like magnetite. Key Points: More than half of Earth's magnetization is hidden in the sense that it generates no observable magnetic field signalUnder few reasonable assumptions, we uniquely recover most of Earth's hidden magnetization from a lithospheric magnetic field modelRecovering the hidden part of Earth's magnetization enables a better link to the underlying internal processes [ABSTRACT FROM AUTHOR]

This article documents the public availability of transcriptomic resources for (i) the Hazelnut tree (Corylus avellana L.) and (ii) the oriental rat flea and primary plague vector, Xenopsylla cheopis. [ABSTRACT FROM AUTHOR]