In situ relationships between microbiota and potential pathobiota in Arabidopsis thaliana.

A current challenge in microbial pathogenesis is to identify biological control agents that may prevent and/or limit host invasion by microbial pathogens. In natura, hosts are often infected by multiple pathogens. However, most of the current studies have been performed under laboratory controlled conditions and by taking into account the interaction between a single commensal species and a single pathogenic species. The next step is therefore to explore the relationships between host-microbial communities (microbiota) and microbial members with potential pathogenic behavior (pathobiota) in a realistic ecological context. In the present study, we investigated such relationships within root-associated and leaf-associated bacterial communities of 163 ecologically contrasted Arabidopsis thaliana populations sampled across two seasons in southwest of France. In agreement with the theory of the invasion paradox, we observed a significant humped-back relationship between microbiota and pathobiota α-diversity that was robust between both seasons and plant organs. In most populations, we also observed a strong dynamics of microbiota composition between seasons. Accordingly, the potential pathobiota composition was explained by combinations of season-specific microbiota operational taxonomic units. This result suggests that the potential biomarkers controlling pathogen\u27s invasion are highly dynamic

Towards a characterisation of the wild legume bitter vetch (Lathyrus linifolius L. (Reichard) Bassler): heteromorphic seed germination, root nodule structure and N-fixing rhizobial symbionts:heteromorphic seed germination, root nodule structure and N-fixing rhizobial symbionts

Lathyrus linifolius L. (Reichard) Bässler (bitter vetch) is a fabaceous nitrogen (N) fixing species. A coloniser of low nutrient (N) soils it supports biodiversity such as key moth and butterfly species and its roots are known for their organoleptic and claimed therapeutic properties. Thus, the species has high potential for restoration, conservation, novel cropping and as model species. The latter owing to its genetic synteny with important pulse crops. However, regeneration and functional attributes of L. linifolius remain to be characterised. Seeds of L. linifolius were characterised using physical, colourimetric and chemical data. Ultrastructural and functional characterisation of the N fixing root nodules included immunolabelling with nifH-protein antibodies (recognising the N fixing enzyme, nitrogenase). Endosymbiotic bacteria were isolated from the root nodules and characterised phylogenetically using 16S rRNA, nodA and nodD gene sequeneces. L. linifolius yielded hetermorphic seeds of distinct colour classes: green and brown. Seed morphotypes had similar carbon:N ratios and were equally germinable (ca. 90%) after scarification at differing optimal temperatures (16 and 20°C, respectively). Brown seeds were larger and comprised a larger proportion of the seed batch (69%). L. linifolius root nodules appeared indeterminate in structure, effective (capable of fixing atmospheric N) and accommodated strains with high similarity to Rhizobium leguminosarum biovar viciae. The findings and rhizobial isolates have potential application for ecological restoration and horticulture using native seeds. Also, the data and rhizobial resources have potential application in comparative and functional studies with related and socio-economically important crops such as Pisum, Lens and Vicia

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care

Drug-target network in myocardial infarction reveals multiple side effects of unrelated drugs

The systems-level characterization of drug-target associations in myocardial infarction (MI) has not been reported to date. We report a computational approach that combines different sources of drug and protein interaction information to assemble the myocardial infarction drug-target interactome network (My-DTome). My-DTome comprises approved and other drugs interlinked in a single, highly-connected network with modular organization. We show that approved and other drugs may both be highly connected and represent network bottlenecks. This highlights influential roles for such drugs on seemingly unrelated targets and pathways via direct and indirect interactions. My-DTome modules are associated with relevant molecular processes and pathways. We find evidence that these modules may be regulated by microRNAs with potential therapeutic roles in MI. Different drugs can jointly impact a module. We provide systemic insights into cardiovascular effects of non-cardiovascular drugs. My-DTome provides the basis for an alternative approach to investigate new targets and multidrug treatment in MI

Comparison of Hepatic-like Cell Production from Human Embryonic Stem Cells and Adult Liver Progenitor Cells: CAR Transduction Activates a Battery of Detoxification Genes

In vitro production of human hepatocytes is of primary importance in basic research, pharmacotoxicology and biotherapy of liver diseases. We have developed a protocol of differentiation of human embryonic stem cells (ES) towards hepatocyte-like cells (ES-Hep). Using a set of human adult markers including CAAT/enhancer binding protein (C/EBPalpha), hepatocyte nuclear factor 4/7 ratio (HNF4alpha1/HNF4alpha7), cytochrome P450 7A1 (CYP7A1), CYP3A4 and constitutive androstane receptor (CAR), and fetal markers including alpha-fetoprotein, CYP3A7 and glutathione S-transferase P1, we analyzed the expression of a panel of 41 genes in ES-Hep comparatively with human adult primary hepatocytes, adult and fetal liver. The data revealed that after 21 days of differentiation, ES-Hep are representative of fetal hepatocytes at less than 20 weeks of gestation. The glucocorticoid receptor pathway was functional in ES-Hep. Extending protocols of differentiation to 4 weeks did not improve cell maturation. When compared with hepatocyte-like cells derived from adult liver non parenchymal epithelial (NPE) cells (NPE-Hep), ES-Hep expressed several adult and fetal liver makers at much greater levels (at least one order of magnitude), consistent with greater expression of liver-enriched transcription factors Forkhead box A2, C/EBPalpha, HNF4alpha and HNF6. It therefore seems that ES-Hep reach a better level of differentiation than NPE-Hep and that these cells use different lineage pathways towards the hepatic phenotype. Finally we showed that lentivirus-mediated expression of xenoreceptor CAR in ES-Hep induced the expression of several detoxification genes including CYP2B6, CYP2C9, CYP3A4, UDP-glycosyltransferase 1A1, solute carriers 21A6, as well as biotransformation of midazolam, a CYP3A4-specific substrate

Phylogeny in Aid of the Present and Novel Microbial Lineages: Diversity in Bacillus

Bacillus represents microbes of high economic, medical and biodefense importance. Bacillus strain identification based on 16S rRNA sequence analyses is invariably limited to species level. Secondly, certain discrepancies exist in the segregation of Bacillus subtilis strains. In the RDP/NCBI databases, out of a total of 2611 individual 16S rDNA sequences belonging to the 175 different species of the genus Bacillus, only 1586 have been identified up to species level. 16S rRNA sequences of Bacillus anthracis (153 strains), B. cereus (211 strains), B. thuringiensis (108 strains), B. subtilis (271 strains), B. licheniformis (131 strains), B. pumilus (83 strains), B. megaterium (47 strains), B. sphaericus (42 strains), B. clausii (39 strains) and B. halodurans (36 strains) were considered for generating species-specific framework and probes as tools for their rapid identification. Phylogenetic segregation of 1121, 16S rDNA sequences of 10 different Bacillus species in to 89 clusters enabled us to develop a phylogenetic frame work of 34 representative sequences. Using this phylogenetic framework, 305 out of 1025, 16S rDNA sequences presently classified as Bacillus sp. could be identified up to species level. This identification was supported by 20 to 30 nucleotides long signature sequences and in silico restriction enzyme analysis specific to the 10 Bacillus species. This integrated approach resulted in identifying around 30% of Bacillus sp. up to species level and revealed that B. subtilis strains can be segregated into two phylogenetically distinct groups, such that one of them may be renamed

Drug-Induced Fulminant Hepatitis in a Child Treated for Latent Multidrug-Resistant Tuberculosis With Dual Therapy Combining Pyrazinamide and Levofloxacin

We report the case of a 10-year-old child treated for latent tuberculosis infection (LTBI) with pyrazinamide (PZA) and levofloxacin after contact with a smear-positive multidrug-resistant tuberculosis adult. Over the course of the treatment, the patient developed a drug-induced fulminant hepatitis attributed to the combination of PZA and levofloxacin. This case highlights the hepatotoxicity of the association of second-line anti-TB treatment in children

Pulmonary Infantile Hemangioma Mimicking a Congenital Cystic Adenomatoid Malformation

International audienceInfantile hemangioma (IH) is the most common benign vascular tumor of infancy, occurring predominantly in the head and neck. It is characterized by specific endothelial expression of glucose transporter-1 (GLUT-1) and involution with time, spontaneous or on beta-blockers treatment. Although some predisposing factors are known, the exact pathogenesis remains unclear. We report a case of pulmonary IH GLUT-1 positive, initially suspected as a cystic pulmonary airway malformation, in a child presenting with both cardiac and renal malformations. The clinical, radiological, pathological, and genetics findings are discussed with a review of the literature. Although pulmonary IH is a rare lesion, it should be suspected when facing a pulmonary cystic mass in a child