Comparative Pathogenomics Reveals Horizontally Acquired Novel Virulence Genes in Fungi Infecting Cereal Hosts

Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens

Using online screening in the general population to detect participants at clinical high-risk for psychosis

Introduction: Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated. Methods: We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups. Conclusion: These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

A Pilot Study of the Acute Ingestion of No. 1 Rosemary Water: Evidence of Cognitive, Physiological and Subjective Effects in Healthy Adults

This study investigated the potential impact of the acute ingestion of No. 1 Rosemary water—a commercially available carbonated water containing an extract of Rosemary (Rosmarinus officinalis). Twenty healthy adults were randomly allocated to consume either 330 ml of No. 1 Rosemary water or plain carbonated water. They then completed a series of subjective measures and cognitive tasks including a fifteen-minute session on a stress inducing multi-tasking framework, followed by a second completion of the subjective measures. Heart rate and blood pressure were monitored throughout the procedure. Given the pilot nature of the study, analysis of the data eschewed significance testing for the calculation of Cohen’s d measure of effect sizes. These revealed a number of small enhancement effects on cognition, consistent with those found previously for the inhalation of the aroma of Rosemary essential oil, and oral administration of dried herb. Of particular interest here are the reduced subjective evaluations of stress, and the blunted physiological reactivity noted for heart rate and blood pressure, which represent novel findings in this area. Taken together the data suggest further investigation of this product is warranted with regard to its potential beneficial properties

Locating 'power' in wind power planning processes: the (not so) influential role of local objectors

There have been conflicting accounts of the role and influence of local opposition within planning application outcomes for wind power developments. There is an expanding literature that considers public responses to proposed renewable energy developments and much of this suggests that public opposition is a key factor in the slow growth in renewable energy capacity. However, this paper will show that local opposition groups' power over such planning processes is very limited, and in fact extends only so far as delaying an outcome. Through a thematic content analysis of objection letters to one particular proposed wind power development, the key issues raised in connection with the development will be highlighted. Subsequently, these issues will be compared with those discussed in the official report of the planning appeals process, and it will be shown that the concerns of local objectors had little influence over the eventual verdict.renewable energy, power, planning, objections,

Summary of the <i>F. pseudograminearum</i> genome sequence assembly in comparison to selected fungal genome sequences obtained by short-read sequencing and the reference genome for <i>F. graminearum</i>.

*<p>not provided.</p>†<p>85× coverage with Illumina and 10× with 454.</p

Phylogram of fungal amidohydrolases found in <i>F. pseudograminearum</i> that appear to be of bacterial origin and a number of bacterial amidohydrolases.

<p>Fungal sequences are highlighted in grey boxes. Numbers on branches indicate approximate likelihood ratio test branch support values.</p

Alignment between <i>F. graminearum</i> and <i>F. pseudograminearum</i>.

<p><i>F. graminearum</i> chromosomes are ordered in decreasing size. (A) Dot-plot representing a whole genome alignment between <i>F. graminearum</i> isolate Ph1 and <i>F. pseudograminearum</i> isolate CS3096. The alignment was generated with NUCmer, part of the MUMmer 3 comparative sequence analysis package. Sequences were pre-masked for known repetitive elements and simple repeats using RepeatMasker. The dot plot represents the best 1∶1 alignment between the two genomes. Dots closest to the diagonal represent co-linearity between the two genomes. Red represents matches in the forward direction and blue is indicative of inversions in part of the mapped contig relative to the <i>F. graminearum</i> genome. (B) Distribution of gaps in the alignment between <i>F. pseudograminearum</i> and <i>F. graminearum</i>, relative to the <i>F. graminearum</i> genome. <i>F. graminearum</i> chromosomes were divided into 100 Kbp non-overlapping windows and the unaligned nucleotides in each window summed and expressed as a percentage.</p

Statistical parsimony haplotype network for <i>FpAH1</i>/<i>PnAH1</i> in <i>Fusarium pseudograminearum</i> and <i>Phaeosphaeria</i> spp. Haplotype bubbles are proportional to sample size shown in parentheses.

<p>Dots on line segments indicate single point mutations.</p