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Iron reduction and sulfate reduction often occur simultaneously in anoxic systems, and where that is the case, the molar ratio between the reactions (i.e., Fe/SO42- reduced) influences their impact on water quality and carbon storage. Previous research has shown that pH and the supply of electron donors and acceptors affect that ratio, but it is unclear how their influences compare and affect one another. This study examines impacts of pH and the supply of acetate, sulfate, and goethite on the ratio of iron to sulfate reduction in semi-continuous sediment bioreactors. We examined which parameter had the greatest impact on that ratio and whether the parameter influences depended on the state of each other. Results show that pH had a greater influence than acetate supply on the ratio of iron to sulfate reduction, and that the impact of acetate supply on the ratio depended on pH. In acidic reactors (pH 6.0 media), the ratio of iron to sulfate reduction decreased from 3:1 to 2:1 as acetate supply increased (0-1 mM). In alkaline reactors (pH 7.5 media), iron and sulfate were reduced in equal proportions, regardless of acetate supply. Secondly, a comparison of experiments with and without sulfate shows that the extent of iron reduction was greater if sulfate reduction was occurring and that the effect was larger in alkaline reactors than acidic reactors. Thus, the influence of sulfate supply on iron reduction extent also depended on pH and suggests that iron reduction grows more dependent on sulfate reduction as pH increases. Our results compare well to trends in groundwater geochemistry and provide further evidence that pH is a major control on iron and sulfate reduction in systems with crystalline (oxyhydr)oxides. pH not only affects the ratio between the reactions but also the influences of other parameters on that ratio.

Methanogenesis and iron reduction play major roles in determining global fluxes of greenhouse gases. Despite their importance, environmental factors that influence their interactions are poorly known. Here, we present evidence that pH significantly influences the balance between each reaction in anoxic environments that contain ferric (oxyhydr)oxide minerals. In sediment bioreactors that contained goethite as a source of ferric iron, both iron reduction and methanogenesis occurred but the balance between them varied significantly with pH. Compared to bioreactors receiving acidic media (pH 6), electron donor oxidation was 85% lower for iron reduction and 61% higher for methanogenesis in bioreactors receiving alkaline media (pH 7.5). Thus, methanogenesis displaced iron reduction considerably at alkaline pH. Geochemistry data collected from U.S. aquifers demonstrate that a similar pattern also exists on a broad spatial scale in natural settings. In contrast, in bioreactors that were not augmented with goethite, clay minerals served as the source of ferric iron and the balance between each reaction did not vary significantly with pH. We therefore conclude that pH can regulate the relative contributions of microbial iron reduction and methanogenesis to carbon fluxes from terrestrial environments. We further propose that the availability of ferric (oxyhydr)oxide minerals influences the extent to which the balance between each reaction is sensitive to pH. The results of this study advance our understanding of environmental controls on microbial methane generation and provide a basis for using pH and the occurrence of ferric minerals to refine predictions of greenhouse gas fluxes.

Risk assessment and risk prediction have become essential in the prevention of cardiovascular disease. Even though risk prediction tools are recommended in the European guidelines, they are not adequately implemented in clinical practice. Risk prediction tools are meant to estimate prognosis in an unbiased and reliable way and to provide objective information on outcome probabilities. They support informed treatment decisions about the initiation or adjustment of preventive medication. Risk prediction tools facilitate risk communication to the patient and their family, and this may increase commitment and motivation to improve their health. Over the years many risk algorithms have been developed to predict 10-year cardiovascular mortality or lifetime risk in different populations, such as in healthy individuals, patients with established cardiovascular disease and patients with diabetes mellitus. Each risk algorithm has its own limitations, so different algorithms should be used in different patient populations. Risk algorithms are made available for use in clinical practice by means of - usually interactive and online available - tools. To help the clinician to choose the right tool for the right patient, a summary of available tools is provided. When choosing a tool, physicians should consider medical history, geographical region, clinical guidelines and additional risk measures among other things. Currently, the website is the only risk prediction tool providing prediction algorithms for all patient categories, and its implementation in clinical practice is suggested/advised by the European Association of Preventive Cardiology. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this paper was produced within the framework of the ESC Prevention of Cardiovascular Disease Programme which is led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP). The ESC Prevention of Cardiovascular Disease Programme is supported by unrestricted educational grants. The authors received no financial support for the research, authorship, and/or publication of this article. Rossello, X (corresponding author), Ctr Nacl Invest Cardiovasc CNIC Carlos III, Melchor Fernandez Almagro 3, Madrid 28029, Spain. fjrossello@cnic.es

Chemical investigation of the leaves of Manniophyton fulvum led to the isolation of seven flavonoid glycosides: myricetin-3-O-β- Dd -rhamnoside (1), kaempferol-3-O-β- d -rhamnoside (2), quercetin-3-O-β- d -glucoside (3), quercetin-3-O-β- d -rhamnoside (4), quercetin-3-O-β- d -galactoside (5), rutin (6) and quercetin (7). The structures of the compounds were established by spectroscopic analyses as well as by comparison with published data. Some of the compounds showed strong antioxidant activity which validates the traditional use of the plant. An attempted correlation between the computed HOMO-LUMO energies and the measured antioxidant activities was established. We have also estimated the cardiotoxicity of the compounds by calculating the predicted logarithm of the human Ether-`a-go-go Related Gene (loghERG) using the QikProp program. These purified flavonoids are new potential lead compounds for the development of antioxidant drugs.

Glucosylceramides (GlcCer), glucose-conjugated sphingolipids, are major components of the endomembrane system and plasma membrane in most eukaryotic cells. Yet the quantitative significance and cellular functions of GlcCer are not well characterized in plants and other multi-organ eukaryotes. To address this, we examined Arabidopsis lines that were lacking or deficient in GlcCer by insertional disruption or by RNA interference (RNAi) suppression of the single gene for GlcCer synthase (GCS, At2g19880), the enzyme that catalyzes GlcCer synthesis. Null mutants for GCS (designated 'gcs-1') were viable as seedlings, albeit strongly reduced in size, and failed to develop beyond the seedling stage. Heterozygous plants harboring the insertion allele exhibited reduced transmission through the male gametophyte. Undifferentiated calli generated from gcs-1 seedlings and lacking GlcCer proliferated in a manner similar to calli from wild-type plants. However, gcs-1 calli, in contrast to wild-type calli, were unable to develop organs on differentiation media. Consistent with a role for GlcCer in organ-specific cell differentiation, calli from gcs-1 mutants formed roots and leaves on media supplemented with the glucosylated sphingosine glucopsychosine, which was readily converted to GlcCer independent of GCS. Underlying these phenotypes, gcs-1 cells had altered Golgi morphology and fewer cisternae per Golgi apparatus relative to wild-type cells, indicative of protein trafficking defects. Despite seedling lethality in the null mutant, GCS RNAi suppression lines with ≤2% of wild-type GlcCer levels were viable and fertile. Collectively, these results indicate that GlcCer are essential for cell-type differentiation and organogenesis, and plant cells produce amounts of GlcCer in excess of that required for normal development.

The class IV homeodomain leucine zipper transcription factor GLABRA2 (GL2) acts in a complex regulatory circuit that regulates the differentiation of trichomes in Arabidopsis thaliana. We describe a genetic interaction with HOMEODOMAIN GLABROUS11 (HDG11), previously identified as a negative regulator of trichome branching. gl2 hdg11 double mutants display enhanced trichome cell-type differentiation defects. Transgenic expression of HDG11 using the GL2 promoter partially suppresses gl2 trichome phenotypes. Vice versa, expression of GL2 under the control of its native promoter partially complements hdg11 ectopic branching. Since gl2 hdg11 and gl2 myb23 double mutants and the triple mutant display similar trichome differentiation defects, we investigated a connection to the R2R3-MYB transcription factor MYB23. We show that MYB23 transcript levels are significantly reduced in shoots from gl2 mutants and that GL2 can drive the expression of a MYB23-promoter fusion to green fluorescent protein. Yeast one-hybrid, chromatin immunoprecipitation, and in planta reporter gene experiments indicate that an L1-box in the MYB23 promoter acts as a GL2 binding site. Taken together, our findings reveal a functional redundancy between GL2 and HDG11, two homeodomain leucine zipper transcription factors previously thought to mediate opposing functions in trichome morphogenesis. A model is proposed in which GL2 transcript levels are maintained through a positive feedback loop involving GL2 activation of MYB23.

Two fungal-secreted α-fucosidases and their genes were characterized. FoFCO1 was purified from culture filtrates of Fusarium oxysporum strain 0685 grown on l-fucose and its encoding gene identified in the sequenced genome of strain 4287. FoFCO1 was active on p-nitrophenyl-α-fucoside (pNP-Fuc), but did not defucosylate a nonasaccharide (XXFG) fragment of pea xyloglucan. A putative α-fucosidase gene (FgFCO1) from Fusarium graminearum was expressed in Pichia pastoris. FgFCO1 was ∼1,800 times less active on pNP-Fuc than FoFCO1, but was able to defucosylate the XXFG nonasaccharide. Although FgFCO1 and FoFCO1 both belong to Glycosyl Hydrolase family 29, they share

Based on the analysis of its genome sequence, the ectomycorrhizal (ECM) basidiomycetous fungus Laccaria bicolor was shown to be lacking many of the major classes of secreted enzymes that depolymerize plant cell wall polysaccharides. To test whether this is also a feature of other ECM fungi, we searched a survey genome database of Amanita bisporigera with the proteins found in the secretome of Trichoderma reesei (syn. Hypocrea jecorina), a biochemically well-characterized industrial fungus. Additional proteins were also used as queries to compensate for major groups of cell-wall-degrading enzymes lacking in the secretome of T. reesei and to substantiate conclusions drawn from the T. reesei collection. By MS/MS-based “shotgun” proteomics, 80 proteins were identified in culture filtrates of T. reesei strain RUTC30 grown on corn cell walls and in a commercial “cellulase” preparation, Spezyme CP. The two T. reesei enzyme preparations were qualitatively and quantitatively similar, the most striking difference being the lack of at least five major peptidases from the commercial enzyme mixture. Based on our analysis of A. bisporigera, this ECM fungus is deficient in many major classes of cell-wall-degrading enzymes, including both glycosyl hydrolases and carbohydrate esterases. By comparison, the genomes of the saprophytic basidiomycetes Coprinopsis cinerea and Galerina marginata (using a genome survey sequence approximately equivalent in depth to that of A. bisporigera) have, like T. reesei, a much more complete complement of cell-wall-degrading enzymes.

Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.

Angiogenesis is a strictly controlled process in the healthy, adult human body. It is regulated by a variety of endogenous angiogenic and angiostatic factors. It is only switched on, e.g., during wound healing. Pathological angiogenesis occurs, for example, in cancer, chronic inflammation, or atherosclerosis. Angiogenesis inhibitors are able to interfere with various steps of angiogenesis, like basement destruction of blood vessels, proliferation and migration of endothelial cells, or the lumen formation. Among the known angiogenesis inhibitors compounds derived from natural sources, like flavonoids, sulphated carbohydrates, or triterpenoids are playing a prominent role.

LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01). Images Figure 2

Antiangiogenic compounds are gaining more and more interest as a new approach in the prevention and treatment of cancer and inflammatory diseases. The objective of this study was the evaluation of the antiangiogenic effect of a red clover extract (RCE) used in food supplements for menopausal complaints as well as of its main isoflavones in an in vivo system, the chorioallantoic membrane assay of fertilized hen's eggs. At a dosage of 250 microg/pellet the red clover extract showed excellent inhibition of angiogenesis. The antiangiogenic activity of the non-methylated isoflavones daidzein and genistein was higher than that of the methylated compounds formononentin and biochanin A. The results demonstrate that RCE is not only suitable for menopausal complaints, but might also be a powerful chemopreventive agent against chronic diseases e.g. which have a high incidence especially in elderly female.

Myocilin is a 55-57kDa secreted glycoprotein and member of the olfactomedin family, which is mutated in some forms of primary open-angle glaucoma. To assess the effects of elevated amounts of myocilin on aqueous humor outflow dynamics in an in vivo system, transgenic betaB1-crystallin-MYOC mice have been developed that strongly overexpress myocilin in their eyes. The transgenic overexpression of myocilin results in an almost five-fold increase of secreted normal myocilin in the aqueous humor of betaB1-crystallin-MYOC mice. In the present study, we wanted to use betaB1-crystallin-MYOC as a tool to identify the response of ocular tissues to the presence of higher than normal amounts of myocilin, and to identify changes in gene expression that could help to shed light on the functional in vivo properties of myocilin. RNA was isolated from ocular tissues of betaB1-crystallin-MYOC mice and wild-type littermates. Changes in gene expression were determined by hybridization of gene microarrays and confirmed by real time RT-PCR and Western blotting. The expression of genes that had been found to be differentially regulated in betaB1-crystallin-MYOC mice was further analyzed in cultured human trabecular meshwork (HTM) cells treated with recombinant myocilin. Although betaB1-crystallin-MYOC mice do not have an obvious phenotype, a statistically significant up- and downregulation of several distinct genes was found when compared to gene expression in wild-type littermates. Among the genes that were found to be differentially regulated were Wasl, Ceacam1, and Spon2, which are involved in cell adhesion and cell-matrix interactions. Differences in expression were also found for Six1 which encodes for a transcription factor, and for Pftk1 whose gene product is a cdc2-related protein kinase. The expression of these genes was also found to be regulated in vitro in HTM cells treated with recombinant myocilin. Substantially higher amounts in ocular tissues of betaB1-crystallin-MYOC mice were found for connexin 46 and alphaB-crystallin. In addition, several genes that encode for olfactomedin proteins showed distinct changes in expression. Olfml3 was significantly downregulated, while Lphn1, Lphn2, and Lphn3 were significantly upregulated. Our findings support a role for myocilin in modulating cellular adhesion, and suggest functional processes that involve other proteins of the olfactomedin family.

Nanoarchaeum equitansandIgnicoccus hospitalisrepresent a unique, intimate association of two archaea. Both form a stable coculture which is mandatory forN.equitansbut not for the hostI.hospitalis. Here, we investigated interactions and mutual influence between these microorganisms. Fermentation studies revealed that during exponential growth only about 25% ofI.hospitaliscells are occupied byN.equitanscells (one to three cells). The latter strongly proliferate in the stationary phase ofI.hospitalis, until 80 to 90% of theI.hospitaliscells carry around 10N.equitanscells. Furthermore, the expulsion of H2S, the major metabolic end product ofI.hospitalis, by strong gas stripping yields huge amounts of freeN.equitanscells.N.equitanshad no influence on the doubling times, final cell concentrations, and growth temperature, pH, or salt concentration ranges or optima ofI.hospitalis. However, isolation studies using optical tweezers revealed that infection withN.equitansinhibited the proliferation of individualI.hospitaliscells. This inhibition might be caused by deprivation of the host of cell components like amino acids, as demonstrated by13C-labeling studies. The strong dependence ofN.equitansonI.hospitaliswas affirmed by live-dead staining and electron microscopic analyses, which indicated a tight physiological and structural connection between the two microorganisms. No alternative hosts, including otherIgnicoccusspecies, were accepted byN.equitans. In summary, the data show a highly specialized association ofN.equitansandI.hospitaliswhich so far cannot be assigned to a classical symbiosis, commensalism, or parasitism.

A novel chemolithoautotrophic and hyperthermophilic member of the genus Ignicoccus was isolated from a submarine hydrothermal system at the Kolbeinsey Ridge, to the north of Iceland. The new isolate showed high similarity to the two species described to date, Ignicoccus islandicus and Ignicoccus pacificus, in its physiological properties as well as in its unique cell architecture. However, phylogenetic analysis and investigations on the protein composition of the outer membrane demonstrated that the new isolate was clearly distinct from I. islandicus and I. pacificus. Furthermore, it is the only organism known so far which is able to serve as a host for ‘Nanoarchaeum equitans’, the only cultivated member of the ‘Nanoarchaeota’. Therefore, the new isolate represents a novel species of the genus Ignicoccus, which we name Ignicoccus hospitalis sp. nov. (type strain KIN4/IT=DSM 18386T=JCM 14125T).

Tridax procumbens , is a common annual weed in the West African sub-region and other tropical zones of the world and is known as “coat buttons”. Traditional medical practitioners (TMPs) and the native peoples of these areas use the leaves of the plant as a remedy against several ailments ranging from conjunctivitis, diarrhoea, and dysentery to wound healing and related inflammatory conditions. Preliminary radical scavenging screenings proved positive and prompted further investigations into its anti-oxidant and anti-inflammatory activities. This, then necessitated the use of DPPH (2,2-diphenyl-1-picrylhydrazyl hydrate) and HET-CAM (Hen\'s egg chorioallanthoic membrane) assays to investigate the radical scavenging and anti-inflammatory potentials of the plant. The results indicated that the chloroform (CHL) and the aqueous (AQU) fractions had the highest and the lowest 50 % inhibitory concentration of free radical oxidative species (FROS) at 1.92 and 4.22μg/mL in the DPPH assay. The HET-CAM (Hen\'s eggs test on chorioallanthoic membrane) assay, a novel assay for anti-inflammatory evaluation revealed the ethylacetate (ETA) fraction as the most active: 96%: “very strong effect” in terms of restoration of an induced inflammatory condition, while the ethanol extract (ETH) showed 92%: “strong effect”. The aqueous (AQU), the Hexane (HEX) and the chloroform (CHL) fractions displayed a below 25 % inhibition. Serial dilutions of the most active fraction: the ethylacetate fraction (ETA) revealed a dose dependent trend. Chemical analysis of the whole plant showed the presence of flavonoids and alkaloids in the chloroform (CHL) and ethylacetate (ETA) fractions. Interestingly, these classes of natural products have been implicated in radical scavenging and inflammation activities in other studies and it is therefore probable that, they may be playing similar functions in Tridax procumbens and consequently would have justified its uses in traditional medical practices. Key words: Anti-oxidant, anti-inflammatory, HET-CAM, DPPH assay, Asteraceae, Tridax procumbens. Nigerian Journal of Physiological Sciences Vol.18(1-2) 2003: 39-43

WOS: 000188262800014, PubMed ID: 14713159, Phlomis linearis Boiss. & Bal. of the Lamiaceae family growing in central, east and southeast Anatolia is an endemic species for Turkey. The essential oil obtained from the aerial parts by hydro distillation was subsequently analyzed by GC/MS. The main components of the oil were found as beta-caryophyllene (24.2%), germacrene D (22.3%) and caryophyllene oxide (9.2%), among 49 identified compounds, representing 94.5% of the total essential oil. The overall biological activity of the essential oil (100 mug/pellet) was tested on the chorioallantoic membrane (CAM) of the fertilized hen's egg in order to examine the anti-angiogenic and anti-inflammatory activity. None of the tests showed pronounced activity, toxicity or irritation at the tested concentration.

Human papillomavirus (HPV) was detected by using two sets of deoxyribonucleotide primers for differentiating between 'low-risk' types (HPV11 and HPV6) and 'high-risk' (hri) types (HPV16, HPV18 and HPV33). A new application of the Chemiprobe method for labeling DNA was used to detect products of the polymerase chain reaction (PCR) from 36 cervical biopsies. This method, first demonstrated by Uchimura et al. (submitted), is based on the sulfonation of a polycytidylic acid tail of 5-20 monomers attached to the 5' end of either one or both of the PCR primers. This procedure can increase the sensitivity of detection of PCR products more than 100-fold with respect to ethidium bromide (EtdBr) staining. Various methods were used to detect hri HPV DNA in the 36 clinical samples. The number of positive results obtained was as follows, two by Southern-blot hybridization; five by PCR amplification followed by electrophoresis and detection of products by EtdBr staining; six by PCR amplification using one or two sulfonated C-tailed primers followed by electroblotting and immunoenzymatic visualization; and five by hybridization of sulfonated genomic viral recombinant with a PCR product immobilized on a membrane. The yield of the PCR product was significantly greater when one of the primers was C-tailed than when both or neither of the primers were C-tailed. PCR employing sulfonated C-tailed oligo primers is very specific and sensitive, and the entire procedure can be employed as a nonradioactive substitute for radioactive dot-blot or Southern-blot hybridization procedures, routinely used for detection of HPV in clinical samples.

Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention., Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.

International audience; The proper tissue-specific regulation of gene expression is essential for development and homeostasis in metazoans. However, the illegitimate expression of normally tissue-restricted genes-like testis- or placenta-specific genes-is frequently observed in tumors; this promotes transformation, but also allows immunotherapy. Two important questions are: how is the expression of these genes controlled in healthy cells? And how is this altered in cancer? To address these questions, we used an unbiased approach to test the ability of 350 distinct genetic or epigenetic perturbations to induce the illegitimate expression of over 40 tissue-restricted genes in primary human cells. We find that almost all of these genes are remarkably resistant to reactivation by a single alteration in signaling pathways or chromatin regulation. However, a few genes differ and are more readily activated; one is the placenta-expressed gene ADAM12, which promotes invasion. Using cellular systems, an animal model, and bioinformatics, we find that a non-canonical but druggable TGF-β/KAT2A/TAK1 axis controls ADAM12 induction in normal and cancer cells. More broadly, our data show that illegitimate gene expression in cancer is an heterogeneous phenomenon, with a few genes activatable by simple events, and most genes likely requiring a combination of events to become reactivated.

Partial migration, when only part of the population migrates seasonally while the other part remains resident on the shared range, is the most common form of migration in ungulates. Migration is often defined by spatial separation of seasonal ranges and consequently, classification of individuals as migrants or residents is usually only based on geographic criteria. However, the underlying mechanism for migration is hypothesized to be movement in response to spatiotemporal resource variability and thus, migrants are assumed to travel an “ecological distance” (ED) or shift their realized ecological niches. While ecological and geographic distances should be related, their relationship may depend on landscape heterogeneity. Here, we tested the utility of ecological niche theory to both classify migratory individuals and to understand the underlying ecological factors for migratory behavior. We developed an integrative approach combining measures in geographic and ecological niche space and used this to classify and explain migratory behavior of 71 annual roe deer (Capreolus capreolus) movement trajectories in five European study areas. First, to assess the utility of the ED concept for classifying migratory behavior, we tested whether roe deer sought the same ecological conditions year-round or moved to different ecological conditions by measuring the annual ED travelled and the seasonal niche overlap using multivariate statistics. Comparing methods to classify migrants and residents based on geographic and ecological niche space, we found that migratory roe deer switched between seasons both in geographic and in ecological dimensions. Second, we tested which seasonal ecological factors separated resident from migrant niches using discriminant analysis and which broad-scale determinants (e.g., spatiotemporal forage variation and population density) predicted migration probability using generalized linear models. Our results indicated that factors describing forage and topographic variability discriminated seasonal migrant from resident niches. Determinants for predicting migration probability included the temporal variation (seasonality) and also the spatial variability of forage patches. Last, we also found suggestive evidence for a positive relationship between population density and migration probability. By applying the ecological niche concept to the study of partial migration in ungulates, our work underlines that partial migration is a form of behavioral plasticity. Key words: behavioral plasticity; Capreolus capreolus; ecological distance; large herbivores; niche switching; Normalized Difference Vegetation Index; partial migration; realized niche; spatiotemporal variation; ungulates

West Nile virus (WNV) is continuously spreading across Europe, and other continents, i.e. North and South America and many other regions of the world. Despite the overall sporadic nature of outbreaks with cases of West Nile neuroinvasive disease (WNND) in Europe, the spillover events have increased and the virus has been introduced into new areas. The high genetic diversity of the virus, with remarkable phenotypic variation, and its endemic circulation in several countries, require an intensification of the integrated and multidisciplinary research efforts built under the 7th Framework Programme of the European Union (FP7). It is important to better clarify several aspects of WNV circulation in Europe, including its ecology, genomic diversity, pathogenicity, transmissibility, diagnosis and control options, under different environmental and socio-economic scenarios. Identifying WNV endemic as well as infection-free areas is becoming a need for the development of human vaccines and therapeutics and the application of blood and organs safety regulations. This review, produced as a joint initiative among European experts and based on analysis of 118 scientific papers published between 2004 and 2014, provides the state of knowledge on WNV and highlights the existing knowledge and research gaps that need to be addressed with high priority in Europe and neighbouring countries.

Key message Pollination is a key step for fruit production. To provide a tool for future in-depth analysis of pollination in chestnut, we describe in detail a chestnut orchard (location, genotype, phenotype and seed-set of all trees). Context Chestnuts, which are insect-pollinated trees, have been massively planted around the world for nut production. Orchards are planted with clonal varieties selected from crosses between the European chestnuts (Castanea sativa) and Japanese chestnuts (C. crenata) or Chinese chestnuts (C. mollissima) because these two last species are tolerant to blight and ink diseases. Aims To characterize chestnut genetic resources and accurately model male and female fitness as well as pollen exchanges in orchards, we characterized all chestnuts of the INRAE chestnut germplasm collection located near Bordeaux (France). Methods All chestnut trees were geolocated and genotyped using 79 SNP and 98 SSR loci. We scored their flowering phenology using chestnut BBCH scale and precisely described their phenotype (height, diameter a breast height (DBH), canopy diameter…), their capacity to produce pollen (flower type, catkins length…) and their fruit production (number of burrs, seed-set…). Results We geolocated 275 trees and genotyped 273 of them. We identified 115 unique genotypes and assigned each genotype to species. To assess phenology, we evaluated 244 trees twice a week, for 6 weeks from early June to mid-July. We also described tree phenotypes with 11 variables, pollen production with 5 variables and fruit production with 3 variables. All measures were recorded in 2018 except seed set that was measured two consecutive years, in 2018 and 2019. Conclusion The data collected is very detailed and allows modelling precisely pollen exchanges between trees. Parts of this data have been successfully published in scientific articles. Data are available at: https://data.inrae.fr/dataset.xhtml?persistentId=doi:10.15454/GSJSWW Associated metadata are available at:https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/02c5ca07-1536-4f89-9a0c-9e8d44a91287

Animal communication has long been thought to be subject to pressures and constraints associated with social relationships. However, our understanding of how the nature and quality of social relationships relates to the use and evolution of communication is limited by a lack of directly comparable methods across multiple levels of analysis. Here, we analysed observational data from 111 wild groups belonging to 26 non-human primate species, to test how vocal communication relates to dominance style (the strictness with which a dominance hierarchy is enforced, ranging from 'despotic' to 'tolerant'). At the individual-level, we found that dominant individuals who were more tolerant vocalized at a higher rate than their despotic counterparts. This indicates that tolerance within a relationship may place pressure on the dominant partner to communicate more during social interactions. At the species-level, however, despotic species exhibited a larger repertoire of hierarchy-related vocalizations than their tolerant counterparts. Findings suggest primate signals are used and evolve in tandem with the nature of interactions that characterize individuals' social relationships. Publisher PDF

Background Diet-related greenhouse gas emissions (GHGe) mainly comes from animal-sourced foods. As progressive changes are more acceptable for a sustainable food transition, we aimed to identify nutritionally adequate and culturally acceptable optimized diets ensuring a gradual reduction in GHGe, using observed diet from a large sample of French adults, while considering the mode of food production (organic vs conventional farming) and the co-production link between milk and beef. Material and method Based on the consumption of 257 organic and conventional foods among 29,413 participants (75% women, age: 53.5 ± 14.0y) of the NutriNet-Sante study, we modelled optimal diets according to GHGe reduction scenarios in 5% steps, from 0 to 50% with nutritional, acceptability, and coproduct constraints, for men, premenopausal and menopausal women separately. Results Gradual GHGe decrease under these constraints led to optimal diets with an overall decrease in animal foods, with marked reductions in dairy products (up to −83%), together with a stable but largely redistributed meat consumption in favor of poultry (up to +182%) and pork (up to +46%) and at the expense of ruminant meat (down to −92%). Amounts of legumes increases dramatically (up to +238%). The greater the reduction in diet-related GHGe, the lower the cumulative energy demand (about −25%) and land use (about −43%). The proportion of organic food increased from ~30% in the observed diets to ~70% in the optimized diets. Conclusion Our results suggest that meeting both nutrient reference value and environmental objectives of up to 50% GHGe reduction requires the reduction of animal foods together with important substitutions between animal food groups, which result in drastic reductions in beef and dairy products. Further research is required to explore alignment with long-term health value and conflict with acceptability, in particular for even greater GHGe reductions.

Leptospirosis, caused by a pathogenic Leptospira bacteria, is the most prevalent zoonosis worldwide and in this context has been extensively investigated through a One Health framework. Diagnosis of human leptospirosis includes molecular and serological tools, with serological Microscopic Agglutination Test (MAT) still being considered as a gold standard. Mammals considered as biological reservoirs include species or populations that are able to maintain chronic infection and shed the bacteria via their urine in the environment. Leptospira bacteria are often investigated using the same diagnosis tool, serological MAT. However, MAT testing of putative animal reservoirs can lead to mis-interpretations as it can signal previous infection and not necessarily bring in robust information regarding the capacity of such sero-positive animals to maintain chronic infection. We use previously published data and present new results on introduced and endemic small mammals to show that MAT should not be used for the identification of reservoirs. By contrast, serological data are informative on the level of exposure of animals occupying a specific environment. Finally, we present a sequential methodology to investigate human leptospirosis in a One Health framework that associates molecular detection in humans and animals, together with MAT of human samples using Leptospira isolates obtained from reservoir animals occurring in the same environment.

Group 2 innate lymphoid cells (ILC2s) represent innate homologs of type 2 helper T cells (TH2) that participate in immune defense and tissue homeostasis through production of type 2 cytokines. While T lymphocytes metabolically adapt to microenvironmental changes, knowledge of human ILC2 metabolism is limited, and its key regulators are unknown. Here, we show that circulating ‘naive’ ILC2s have an unexpected metabolic profile with a higher level of oxidative phosphorylation (OXPHOS) than natural killer (NK) cells. Accordingly, ILC2s are severely reduced in individuals with mitochondrial disease (MD) and impaired OXPHOS. Metabolomic and nutrient receptor analysis revealed ILC2 uptake of amino acids to sustain OXPHOS at steady state. Following activation with interleukin-33 (IL-33), ILC2s became highly proliferative, relying on glycolysis and mammalian target of rapamycin (mTOR) to produce IL-13 while continuing to fuel OXPHOS with amino acids to maintain cellular fitness and proliferation. Our results suggest that proliferation and function are metabolically uncoupled in human ILC2s, offering new strategies to target ILC2s in disease settings., ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.

Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.

Made available in DSpace on 2020-12-12T01:33:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Eucalyptus plantation productivity has increased 4-fold across Brazil as a result of improved genetic selection and intensive silviculture. However, the rate of productivity improvements is slowing and suggests increased production will require planting in areas that have never been previously planted with Eucalyptus with uncertain impacts on local water supplies. This study compares water use and water use efficiency between a drought resistant (E. grandis × E. camaldulensis) and high productivity Eucalyptus clone (E. urophylla) across three sites (dry, mesic and wet) spanning a two-fold precipitation gradient (~600–1350 mm y−1) in Brazil. Each site included a 30% reduced rainfall treatment for each clone to investigate within site response to reduced precipitation. We found that the drought resistant clone used as much or more water than the high productivity clone at all three sites. The drought resistant clone transpired almost 20% percent more water than the high productivity clone at the dry site (3.7 vs. 3.0 m3 y−1) while water use between clones did not differ at the mesic (4.6 vs 4.0 m3 y−1) and wet site (4.0 vs 4.5 m3 y−1). The high productivity clone transpired 54, 46 and 37% of annual precipitation at the dry, mesic and wet sites respectively while the drought resistant clone consumed 67, 47 and 31% of annual precipitation from the dry to the wet site. Although the rain reduction treatments did not impact annual water use for either clone at the dry and mesic sites, there were some differences at a subannual timescale. Rain reduction treatments at the dry site lowered transpiration in the driest, hottest three months for the high productivity clone by 25–32%. Rainfall reduction led to lower water use by the drought resistant clone for only one month during the dry season (18%). The high productivity clone transpired less water (24–26%) in the rainfall reduction treatment at the mesic site during three months and the drought resistant clone transpired 18 and 20% less water in the rainfall reduction treatment during two months. Rainfall reduction reduced annual transpiration by 59% for the high productivity clone at the wet site. Average water use efficiency of the drought resistant clone was almost 70% lower than the high productivity clone at the dry and mesic sites (~5.2 vs. 1.5 kg m−3 y−1) and was due to the combination of low growth and high water use. Higher than expected growth by the drought resistant clone at the wet site resulted in similar water use efficiency between clones (6.3 vs. 5.8 kg m−3 y−1). We discuss potential implications of our findings and highlight several lines of evidence that suggest the drought resistant clone in this study allocates a greater proportion of gross primary productivity below ground allowing it to access deeper reserves of soil water during dry periods. Our results suggest that decisions to plant drought resistant clones in drought prone areas should be carefully considered and also highlight the need for more research on water use and drought tolerance strategies for Eucalyptus clones bred for more arid areas in Brazil. USDA Forest Service Rocky Mountain Research Station, 240 West Prospect Road, Fort Collins Forestry Science and Research Institute (IPEF) Department of Forest Sciences University of Lavras (UFLA), Lavras Department of Forest Science São Paulo State University – UNESP Department of Forest Research and Development Klabin SA, Telêmaco Borba Department of Forest Research and Development International Paper, Mogi Guaçu Department of Forest Science São Paulo State University – UNESP

Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes., Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes. The widest diversity of eukaryotic-like proteins known to date can be found in members of the bacterial genus Legionella, some of which cause a severe pneumonia in humans. The characterization of a number of these proteins shed light on their importance during infection. The subsequent identification of eukaryotic-like genes in the genomes of other amoeba-associated bacteria and bacterial symbionts suggested that eukaryotic-like proteins are a common means of bacterial evasion and communication, shaped by the continuous interactions between bacteria and their protozoan hosts. In this review, we discuss the concept of molecular mimicry using Legionella as an example and show that eukaryotic-like proteins effectively manipulate host cell pathways. The study of the function and evolution of such proteins is an exciting field of research that is leading us toward a better understanding of the complex world of bacterium-host interactions. Ultimately, this knowledge will teach us how host pathways are manipulated and how infections may possibly be tackled.

Background Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset. Methods The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study. Results The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Conclusions Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

The black tiger shrimp (Penaeus monodon) is one of the most prominent farmed crustacean species with an average annual global production of 0.5 million tons in the last decade. To ensure sustainable and profitable production through genetic selective breeding programs, several research groups have attempted to generate a reference genome using short-read sequencing technology. However, the currently available assemblies lack the contiguity and completeness required for accurate genome annotation due to the highly repetitive nature of the genome and technical difficulty in extracting high-quality, high-molecular weight DNA in this species. Here, we report the first chromosome-level whole-genome assembly of P. monodon. The combination of long-read Pacific Biosciences (PacBio) and long-range Chicago and Hi-C technologies enabled a successful assembly of this first high-quality genome sequence. The final assembly covered 2.39 Gb (92.3% of the estimated genome size) and contained 44 pseudomolecules, corresponding to the haploid chromosome number. Repetitive elements occupied a substantial portion of the assembly (62.5%), highest of the figures reported among crustacean species. The availability of this high-quality genome assembly enabled the identification of novel genes associated with rapid growth in the black tiger shrimp through the comparison of hepatopancreas transcriptome of slow-growing and fast-growing shrimps. The results highlighted several gene groups involved in nutrient metabolism pathways and revealed 67 newly identified growth-associated genes. Our high-quality genome assembly provides an invaluable resource for accelerating the development of improved shrimp strain in breeding programs and future studies on gene regulations and comparative genomics.

International audience; ILCs and T cells are closely related functionally but they significantly differ in their ability to circulate, expand, and renew. Cooperation and reciprocal functional regulation suggest that these cell types are more complementary than simply redundant during immune responses. How ILCs shape T-cell responses is strongly dependent on the tissue and inflammatory context. Likewise, indirect regulation of ILCs by adaptive immunity is induced by environmental cues such as the gut microbiota. Here, we review shared requirements for the development and function of both cell types and divergences in the orchestration of prototypic immune functions. We discuss the diversity of functional interactions between T cells and ILCs during homeostasis and immune responses. Identifying the location and the nature of the tissue microenvironment in which these interactions are taking place may uncover the remaining mysteries of their close encounters.

International audience; Parasites of the genus Leishmania infect the mammalian hosts, including mice and humans and cause cutaneous or visceral leishm aniasis depending upon the parasite species transmitted by the vector sandfly. Leishmania amazonensis is one of the Leishmania species responsible for th e cutaneous form of the disease. We have inoculated with these parasites the ear dermis of mice. RNA preparations were performed from fragmented tissues using a buffer containing guanidin isothiocynate (RLT buffer, RNeasy Mini Kit, Qiagen, SAS, France) and β mercaptoethanol. Both reagents facilitate the isolation of intact RNA from tissues and the use of the RNeasy Kits present with several advantages that facilitate the isolation of pure non degraded total RNA: i) T his method allows to avoid the presence o f phenol in the RNA extraction buffer, commonly used in alternative protocols; ii) Moreover Diethylpyrocarbonate (DEPC) treatment of glassware, to avoid RNAses contamination of the samples, is not required with this protocol; iii) F inally, it is a fast pro cedure and the isolated total RNA may be concentrated in a small volume thus facilitating its use for downstream experimental procedures.

International audience; Despite its major role as a global climate regulator, little is known about the recent evolution of the North Atlantic Ocean, especially prior to the fifties, principally because of the lack of long-term instrumental data. Moreover, the North Atlantic Ocean is undergoing rapid changes at the physical scale leading to modifications at the biological scale increasing interest to monitor the environment. The phytoplankton is the base of the ocean life and its perturbation can lead to further changes in the food chain. Recording its dynamics implies to observe both its spatial and temporal variations. This study brings forward the use of the Ba/Ca ratio from shells of the long-living bivalve Arctica islandica collected in the Northwestern Atlantic Ocean near Saint-Pierre and Miquelon (SPM) as a recorder of the past and present phytoplankton dynamics. A high inter and intra-reproducibility and synchrony between Ba/Cashell profiles were demonstrated allowing the reconstruction of a 124 years annually-resolved Ba/Cashell master chronology (from 1893 to 2016). This master chronology was positively correlated to the surface chlorophyll a measured by satellite sensor at regional (around SPM) and global scales (Northwestern Atlantic).

Genome-wide association studies (GWAS) in plants typically suffer from limited statistical power. An alternative to the logistical and cost challenge of increasing sample sizes is to gain power by meta-analysis using information from independent studies. We carried out GWAS for growth traits with six single-marker models and regional heritability mapping (RHM) in four Eucalyptus breeding populations independently and by Joint-GWAS, using gene and segment-based models, with data for 3373 individuals genotyped with a communal EUChip60KSNP platform. While single-single nucleotide polymorphism (SNP) GWAS hardly detected significant associations at high-stringency in each population, gene-based Joint-GWAS revealed nine genes significantly associated with tree height. Associations detected using single-SNP GWAS, RHM and Joint-GWAS set-based models explained on average 3-20% of the phenotypic variance. Whole-genome regression, conversely, captured 64-89% of the pedigree-based heritability in all populations. Several associations independently detected for the same SNPs in different populations provided unprecedented GWAS validation results in forest trees. Rare and common associations were discovered in eight genes involved in cell wall biosynthesis and lignification. With the increasing adoption of genomic prediction of complex phenotypes using shared SNPs and much larger tree breeding populations, Joint-GWAS approaches should provide increasing power to pinpoint discrete associations potentially useful toward tree breeding and molecular applications.

International audience; The major human cytochrome P450 CYP2D6 isoform enzyme plays important roles in the liver and in the brain with regards to xenobiotic metabolism. Xenobiotics as CYP2D6 substrates include a whole range of pharmaceuticals, pesticides and plant alkaloids to cite but a few. In addition, a number of endogenous compounds have been shown to be substrates of CYP2D6 including trace amines in the brain such as tyramine and 5-methoxytryptamine as well as anandamide and progesterone. Because of the polymorphic nature of CYP2D6, considerable inter-phenotypic and inter-ethnic differences in the pharmaco/toxicokinetics (PK/TK) and metabolism of CYP2D6 substrates exist with potential consequences on the pharmacology and toxicity of chemicals. Here, large extensive literature searches have been performed to collect PK data from published human studies for a wide range of pharmaceutical probe substrates and investigate human variability in CYP2D6 metabolism. The computed kinetic parameters resulted in the largest open source database, quantifying inter-phenotypic differences for the kinetics of CYP2D6 probe substrates in Caucasian and Asian populations, to date. The database is available in supplementary material (CYPD6 DB) and EFSA knowledge junction (DOI to added). Subsequently, meta-analyses using a hierarchical Bayesian model for markers of chronic oral exposure (oral clearance, area under the plasma concentration time curve) and acute oral exposure (maximum plasma concentration (Cmax) provided estimates of inter-phenotypic differences and CYP2D6-related uncertainty factors (UFs) for chemical risk assessment in Caucasian and Asian populations classified as ultra-rapid (UM), extensive (EMs), intermediate (IMs) and poor metabolisers (PMs). The model allowed the integration of inter-individual (i.e. inter-phenotypic and inter-ethnic), inter-compound and inter-study variability together with uncertainty in each PK parameter. Key findings include 1. Higher frequencies of PMs in Caucasian populations compared to Asian populations (>8% vs 1-2%) for which EM and IM were the most frequent phenotype. 2. Large inter-phenotypic differences in PK parameters for Caucasian EMs (coefficients of variation (CV) > 50%) compared with Caucasian PMs and Asian EMs and IMs (i.e CV < 40%). 3. Inter-phenotypic PK differences between EMs and PMs in Caucasian populations increase with the quantitative contribution of CYP2D6 for the metabolism (fm) for a range of substrates (fm CYP2D6 range: 20-95% of dose) (range: 1-54) to a much larger extent than those for Asian populations (range: 1-4). 4. Exponential meta-regressions between Fm CYP2D6 in EMs and inter-phenotypic differences were also shown to differ between Caucasian and Asian populations as well as CYP2D6-related UFs. Finally, implications of these results for the risk assessment of food chemicals and emerging designer drugs of public health concern, as CYP2D6 substrates, are highlighted and include the integration of in vitro metabolism data and CYP2D6 variability distributions for the development of quantitative in vitro in vivo extrapolation models.

International audience; Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood–derived CD34+ cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients.

International audience; Nicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome-Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of 'positive allosteric modulators' (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.

At world level, the current official number of large camelids cannot be determined exactly (it is estimated to be more than 35 million heads), and the role of camels in the livestock economy is highly variable. The only reliable statistics are provided by FAO since 1961. According to these data, five different patterns of demographic changes have been observed. In countries marked by a regular or drastic decline of their camelid population, a tendency to re-increase has been in force since the beginning of the century, except in India. Generally, countries marked by a sharp recent increase in their large camelid population have implemented a census and readjusted their data. Many inconsistencies occur in available data, most notably cases arising from changes occurring in state status (for example secession of Eritrea, Soviet Union collapse). Moreover, large camelid stocks in Australia, in countries of new camel establishment (Western countries) and those related to the expansion of camel farming, notably in Africa, are not recorded in the international database. In addition, there is no distinction between dromedary and Bactrian data. The present large camelid population in the world is probably more than 40 million and could reach 60 million after 25 years from now if the current demographic trend is maintained.

Made available in DSpace on 2022-05-01T00:16:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-29 The common black field cricket, Gryllus assimilis (Orthoptera: Gryllidae), damages young plants of red cedar, Juniperus virginiana (Cupressaceae); strawberry, Fragaria × ananassa (Rosaceae); sugarcane, Saccharum officinarum (Poaceae); teak, Tectona grandis (Lamiaceae); upland cotton, Gossypium hirsutum (Malvaceae); and, mainly, Eucalyptus spp. (Myrtaceae). The objective of this study was to investigate the biological and behavioral parameters of this insect in the laboratory and in Eucalyptus spp. plantations in Inhambupe, Bahia State, Brazil. The incubation period and the viability of G. assimilis eggs were 11.87 days and approximately 22%, respectively. The duration of the nymphal stage was 62.34 days with approximately 60% of the nymphs obtained in the laboratory being females. The average number of egg batches per female, eggs per female, and eggs per batch per female of this insect were 25.50, 862.17, and 34.65, respectively. G. assimilis females lived for 76.50 days in the adult stage, and 138.34 days in total, from egg through nymph to adult. Males produced three characteristic sounds: one for the marking of territory, one for courtship, and one when alone. G. assimilis fed primarily on weeds but, in their absence, it damaged young Eucalyptus spp. plants. This paper presents important data on the biology and behavior of G. assimilis; this information may encourage additional biological research, laboratory rearing, and integrated management of this pest. Bracell Ltd., rua Dr. José Tiago Correa, s/n°, bairro Alagoinhas Velha Asia Pacific Resources International Holdings Ltd. (APRIL) PT. Riau Andalan Pulp and Paper (RAPP) Departamento de Ciências Ambientais Universidade Federal de São Carlos Embrapa Florestas Departamento de Proteção Vegetal Universidade Estadual Paulista “Júlio de Mesquita Filho” Departamento de Entomologia/BIOAGRO Universidade Federal de Viçosa Departamento de Proteção Vegetal Universidade Estadual Paulista “Júlio de Mesquita Filho”

Several important vegetable crops grown outdoors in temperate climates in Europe can be damaged by the root-feeding larvae of Diptera (Delia radicum, Delia floralis, Chamaepsila rosae, Delia platura, Delia florilega, Delia antiqua). Knowledge of pest insect phenology is a key component of any Integrated Pest Management (IPM) strategy, and this review considers the methods used to monitor and forecast the occurrence of root-feeding flies as a basis for decision-making by growers and the ways that such information can be applied. It has highlighted some current management approaches where such information is very useful for decision support, for example, the management of C. rosae with insecticidal sprays and the management of all of these pests using crop covers. There are other approaches, particularly those that need to be applied at sowing or transplanting, where knowledge of pest phenology and abundance is less necessary. Going forward, it is likely that the number of insecticidal control options available to European vegetable growers will diminish and they will need to move from a strategy which often involves using a single ‘silver bullet’ to a combination of approaches/tools with partial effects (applied within an IPM framework). For the less-effective, combined methods, accurate information about pest phenology and abundance and reliable decision support are likely to be extremely important.

Forest production efficiency (FPE) metric describes how efficiently the assimilated carbon is partitioned into plants organs (biomass production, BP) or—more generally—for the production of organic matter (net primary production, NPP). We present a global analysis of the relationship of FPE to stand-age and climate, based on a large compilation of data on gross primary production and either BP or NPP. FPE is important for both forest production and atmospheric carbon dioxide uptake. We find that FPE increases with absolute latitude, precipitation and (all else equal) with temperature. Earlier findings—FPE declining with age—are also supported by this analysis. However, the temperature effect is opposite to what would be expected based on the short-term physiological response of respiration rates to temperature, implying a top-down regulation of carbon loss, perhaps reflecting the higher carbon costs of nutrient acquisition in colder climates. Current ecosystem models do not reproduce this phenomenon. They consistently predict lower FPE in warmer climates, and are therefore likely to overestimate carbon losses in a warming climate., Many models assume a universal carbon use efficiency across forest biomes, in contrast to assumptions of other process-based models. Here the authors analyse forest production efficiency across a wide range of climates to show a positive relationship with annual temperature and precipitation, indicating that ecosystem models are overestimating forest carbon losses under warming.

International audience; Yellow Fever (YF) remains a major public health issue in Sub-Saharan Africa and South America, despite the availability of an effective vaccine. In Africa, most YF outbreaks are reported in West Africa. However, urban outbreaks occurred in 2016 in both Angola and the Democratic Republic of Congo (DRC), and imported cases were reported in Chinese workers coming back from Africa. In Central Africa, Cameroon and the Republic of Congo host a high proportion of non-vaccinated populations increasing the risk of urban outbreaks. The main vector is Aedes aegypti and possibly, Aedes albopictus, both being anthropophilic and domestic mosquitoes. Here, we provide evidence that both Ae. aegypti and Ae. albopictus in Cameroon and the Republic of Congo are able to transmit Yellow fever virus (YFV) with higher rates of infection, dissemination, and transmission for Ae. aegypti. We conclude that the potential of both Aedes species to transmit YFV could increase the risk of urban YF transmission and urge public health authorities to intensify their efforts to control domestic vectors, and extend vaccine coverage to prevent major YFV outbreak.

Made available in DSpace on 2020-12-10T19:37:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-04 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Programa Cooperativo sobre Protecao Florestal (PROTEF) of the Instituto de Pesquisas e Estudos Florestais (IPEF) Trichogrammatidae (Hymenoptera) egg parasitoids are released for the fall armyworm Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) management, and weeds are controlled mainly with glyphosate in corn Zea mays L. (Poales: Poaceae) crops. A glyphosate-based herbicide was sprayed at 13.94 L ha(-1) on eggs of the worldwide used alternative host, the Mediterranean flour moth Anagasta kuehniella Zeller (Lepidoptera: Pyralidae) parasitized by 10 Trichogrammatidae species, in a free-choice test. Parasitism, female emergence and female-biased sex ratio of these parasitoids were evaluated. Parasitism by Trichogramma acacioi Brun, Moraes & Soares, Trichogramma bennetti Nagaraja & Nagarkatti, Trichogramma brasiliensis Ashmead, Trichogramma galloi Zucchi, and Trichogramma pretiosum Riley was lower with glyphosate. This herbicide reduced the Trichogrammatoidea annulata de Santis, T. bennetti, Trichogramma bruni Nagaraja, Trichogramma demoraesi Nagaraja, T. galloi, and T. pretiosum female emergence. Female-biased sex ratio of T. annulata, T. bennetti, T. bruni, T. galloi, and T. pretiosum was lower with glyphosate. Glyphosate did not reduce the Trichogramma soaresi Nagaraja parasitism and female emergence, and, therefore, the use of this species has potential to be compatible with glyphosate. Univ Fed Minas Gerais, Inst Ciencias Agr, Insetario GWG de Moraes, BR-39404547 Montes Claros, MG, Brazil Asia Pacific Resources Int Holdings Ltd APRIL, PT Riau Andalan Pulp & Paper RAPP, Riau 28300, Sumatra, Indonesia Inst Fed Norte Minas Gerais, Dept Ciencias Agr, BR-39480000 Januaria, MG, Brazil Univ Estadual Paulista, Dept Protecao Vegetal, BR-18603970 Botucatu, SP, Brazil Univ Fed Vicosa, Dept Entomol BIOAGRO, BR-36570900 Vicosa, MG, Brazil Univ Estadual Paulista, Dept Protecao Vegetal, BR-18603970 Botucatu, SP, Brazil

International audience; Macrophages are key cells of innate immune response and serve as the first line of defense against bacteria. Transcription profiling of bacteria-infected macrophages could provide important insights on the pathogenicity and host defense mechanisms during infection. We have examined transcription profiles of bovine monocyte-derived macrophages (bMDMs) isolated from the blood of 12 animals and infected in vitro with two strains of Streptococcus agalactiae. Illumina sequencing of RNA from 36 bMDMs cultures exposed in vitro to either one of two sequence types of S. agalactiae (ST103 or ST12) for 6 h and unchallenged controls was performed. Analyses of over 1,656 million high-quality paired-end sequence reads revealed 5,936 and 6,443 differentially expressed genes (p < 0.05) in bMDMs infected with ST103 and ST12, respectively, versus unchallenged controls. Moreover, 588 genes differentially expressed between bMDMs infected with ST103 versus ST12 were identified. Ingenuity pathway analysis of the differentially up-regulated genes in the bMDMs infected with ST103 revealed significant enrichment for granulocyte adhesion and diapedesis, while significant enrichment for the phagosome formation pathway was found among down-regulated genes. Moreover, Ingenuity pathway analysis of the differentially up-regulated genes in the bMDMs infected with ST12 showed significant enrichment for type 1/type 2 T helper cell activation, while the complement activation pathway was overrepresented in the down-regulated genes. Our study identified pathogen-induced regulation of key genes and pathways involved in the immune response of macrophages against infection but also likely involved in bacterial evasion of the host immune system. These results may contribute to better understanding of the mechanisms underlying subclinical infection such as bovine streptococcal mastitis.

Preclinical studies of psychiatric disorders use animal models to investigate the impact of environmental factors or genetic mutations on complex traits such as decision-making and social interactions. Here, we introduce a method for the real-time analysis of the behaviour of mice housed in groups of up to four over several days and in enriched environments. The method combines computer vision through a depth-sensing infrared camera, machine learning for animal and posture identification, and radio-frequency identification to monitor the quality of mouse tracking. It tracks multiple mice accurately, extracts a list of behavioural traits of both individuals and the groups of mice, and provides a phenotypic profile for each animal. We used the method to study the impact of Shank2 and Shank3 gene mutations—mutations that are associated with autism—on mouse behaviour. Characterization and integration of data from the behavioural profiles of Shank2 and Shank3 mutant female mice revealed their distinctive activity levels and involvement in complex social interactions. A method that combines a depth-sensing camera and machine learning can track the movements of up to four mice in real time and for several days, extracting both individual and group behavioural traits.

International audience; The human intestine is densely colonized with commensal microbes that stimulate the immune system. While secretory Immunoglobulin (Ig) A is known to play a crucial role in gut microbiota compartmentalization, secretory IgM, and systemic IgG have recently been highlighted in host-microbiota interactions as well. In this review, we discuss important aspects of secretory IgA biology, but rather than focusing on mechanistic aspects of IgA impact on microbiota, we stress the current knowledge of systemic antibody responses to whole gut microbiota, in particular their generation, specificities, and function. We also provide a comprehensive picture of secretory IgM biology. Finally, therapeutic and diagnostic implications of these novel findings for the treatment of various diseases are outlined.

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens.METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk.RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition.CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Several questions remain regarding the timing and nature of the Neanderthal-anatomically modern human (AMH) transition in Europe. The situation in Eastern Europe is generally less clear due to the relatively few sites and a dearth of reliable radiocarbon dates. Claims have been made for both notably early AMH and notably late Neanderthal presence, as well as for early AMH (Aurignacian) dispersal into the region from Central/Western Europe. The Kostenki-Borshchevo complex (European Russia) of Early Upper Paleolithic (EUP) sites offers high-quality data to address these questions. Here we revise the chronology and cultural status of the key sites of Kostenki 17 and Kostenki 14. The Kostenki 17/II lithic assemblage shares important features with Proto-Aurignacian material, strengthening an association with AMHs. New radiocarbon dates for Kostenki 17/II of ∼41–40 ka cal BP agree with new dates for the recently excavated Kostenki 14/IVw, which shows some similarities to Kostenki 17/II. Dates of ≥41 ka cal BP from other Kostenki sites cannot be linked to diagnostic archaeological material, and therefore cannot be argued to date AMH occupation. Kostenki 14's Layer in Volcanic Ash assemblage, on the other hand, compares to Early Aurignacian material. New radiocarbon dates targeting diagnostic lithics date to 39–37 ka cal BP. Overall, Kostenki's early EUP is in good agreement with the archaeological record further west. Our results are therefore consistent with models predicting interregional penecontemporaneity of diagnostic EUP assemblages. Most importantly, our work highlights ongoing challenges for reliably radiocarbon dating the period. Dates for Kostenki 14 agreed with the samples' chronostratigraphic positions, but standard pre-treatment methods consistently produced incorrect ages for Kostenki 17/II. Extraction of hydroxyproline from bone collagen using preparative high-performance liquid chromatography, however, yielded results consistent with the samples' chronostratigraphic position and with the layer's archaeological contents. This suggests that for some sites compound-specific techniques are required to build reliable radiocarbon chronologies.