Host specialisation and disparate evolution of Pyrenophora teres f. teres on barley and barley grass.

Background: Pathogens evolve in an arms race, frequently evolving virulence that defeats resistance genes in their hosts. Infection of multiple hosts may accelerate this virulence evolution. Theory predicts that host diversity affects pathogen diversity, with more diverse hosts expected to harbour more diverse pathogens that reproduce sexually.

Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212).

Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding.

New species of associated with terrestrial orchids in Australia.

Recent studies using sequence data from eight sequence loci and coalescent-based species delimitation methods have revealed several species-level lineages of associated with the orchid genera and in Australia. Here we formally describe three of those species, and spp. nov.

Weeds, as ancillary hosts, pose disproportionate risk for virulent pathogen transfer to crops.

Background: The outcome of the arms race between hosts and pathogens depends heavily on the interactions between their genetic diversity, population size and transmission ability. Theory predicts that genetically diverse hosts will select for higher virulence and more diverse pathogens than hosts with low genetic diversity. Cultivated hosts typically have lower genetic diversity and thus small effective population sizes, but can potentially harbour large pathogen population sizes.

Novel phenylalanine derived diamides as Factor XIa inhibitors.

The synthesis, structural activity relationships (SAR), and selectivity profile of a potent series of phenylalanine diamide FXIa inhibitors will be discussed. Exploration of P1 prime and P2 prime groups led to the discovery of compounds with high FXIa affinity, good potency in our clotting assay (aPPT), and high selectivity against a panel of relevant serine proteases as exemplified by compound 21. Compound 21 demonstrated good in vivo efficacy (EC50=2.

Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.

Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorophenyltetrazole P1 analog, which when combined with further modifications to the linker and P2' group provided compound 32 with FXIa Ki=6.

Phylogenetic and microsatellite markers for Tulasnella (Tulasnellaceae) mycorrhizal fungi associated with Australian orchids.

Premise Of The Study: Phylogenetic and microsatellite markers were developed for Tulasnella mycorrhizal fungi to investigate fungal species identity and diversity. These markers will be useful in future studies investigating the phylogenetic relationship of the fungal symbionts, specificity of orchid-mycorrhizal associations, and the role of mycorrhizae in orchid speciation within several orchid genera. •

Methods And Results: We generated partial genome sequences of two Tulasnella symbionts originating from Chiloglottis and Drakaea orchid species with 454 genome sequencing.

A narrow group of monophyletic Tulasnella (Tulasnellaceae) symbiont lineages are associated with multiple species of Chiloglottis (Orchidaceae): Implications for orchid diversity.

Premise Of The Study: The Orchidaceae is characterized by exceptional species diversity. Obligate orchid mycorrhizae are predicted to determine orchid distributions, and highly specific relationships between orchids and fungi may drive orchid diversification. In this study, mycorrhizal diversity was examined in the terrestrial, photosynthetic orchid genus Chiloglottis to test the hypothesis of mycorrhizal-mediated diversification in the genus Chiloglottis.

Large-scale human metabolic phenotyping and molecular epidemiological studies via 1H NMR spectroscopy of urine: investigation of borate preservation.

Borate is an antibacterial preservative widely used in clinical and large-scale epidemiological studies involving urine sample analysis. Since it readily forms covalent adducts and reversible complexes with hydroxyl and carboxylate groups, the effects of borate preservation in (1)H NMR-spectroscopy-based metabolic profiling of human urine samples have been assessed. Effects of various concentrations of borate (range 0-30 mM) on (1)H NMR spectra of urine were observed at sequential time points over a 12 month period.

Arylphthalazines as potent, and orally bioavailable inhibitors of VEGFR-2.

A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice.

Symbiotic gut microbes modulate human metabolic phenotypes.

Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe-host interactions and the roles of individual bacterial species are obscure. We now demonstrate a"transgenomic" approach to link gut microbiome and metabolic phenotype (metabotype) variation.

Statistical correlation and projection methods for improved information recovery from diffusion-edited NMR spectra of biological samples.

Although NMR spectroscopic techniques coupled with multivariate statistics can yield much useful information for classifying biological samples based on metabolic profiles, biomarker identification remains a time-consuming and complex procedure involving separation methods, two-dimensional NMR, and other spectroscopic tools. We present a new approach to aid complex biomixture analysis that combines diffusion ordered (DO) NMR spectroscopy with statistical total correlation spectroscopy (STOCSY) and demonstrate its application in the characterization of urinary biomarkers and enhanced information recovery from plasma NMR spectra. This method relies on calculation and display of the covariance of signal intensities from the various nuclei on the same molecule across a series of spectra collected under different pulsed field gradient conditions that differentially attenuate the signal intensities according to translational molecular diffusion rates.

Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II.

A novel class of 1-(isoquinolin-5-yl)-4-arylamino-phthalazines is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC(50) as low as 0.017 microM in an HTRF enzymatic assay.

Preparation of substituted pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines via a Pictet-Spengler cyclization.

[Reaction: see text]. A synthesis of the title compounds, which have found use as inhibitors of certain receptor tyrosine kinases, was achieved using a Pictet-Spengler cyclization as a key step.

Gene transfer to plants by diverse species of bacteria.

Agrobacterium is widely considered to be the only bacterial genus capable of transferring genes to plants. When suitably modified, Agrobacterium has become the most effective vector for gene transfer in plant biotechnology. However, the complexity of the patent landscape has created both real and perceived obstacles to the effective use of this technology for agricultural improvements by many public and private organizations worldwide.