A comparison of bioresmethrin, chlorpyrifos-methyl and pimiriphos- methyl as grain protectants against malathion-resistant insects in wheat

Impregnated-paper assays and sprayed-grain assays were used to characterise the potency of candidate grain protectants against malathion-resistant and susceptible strains of Sitophilus oryzae (L.), Rhyzopertha dominica (F.), Tribolium castaneum (Hbst.) and Ephestia cautella (Wlk.). Resistance factors for malathion (as measured by impregnated-paper assays) were 4 for S. oryzae, 6 for R. dominica and 39 for T. castaneum. Of 3 synthetic pyrethroids tested, bioresmethrin was more effective than (1R-trans)-allethrin (bioallethrin) or tetramethrin. All synthetic pyrethroids were particularly effective against R. dominica. The classification of organophosphorus materials in descending order of effectiveness was chlorpyrifos-methyl, pirimiphos-methyl and malathion; these were relatively less potent that the pyrethroids against R. dominica. A level of cross-resistance was demonstrated in resistant strains to the newer compounds, but their high potency indicated the possibility of effective pest control at acceptable dosage rates for the present. The stability of the compounds was investigated by exposing treated wheat to conditions in the upper layers of a bulk stored grain for up to 25 weeks. Combinations of chlorpyrifos-methyl or pirimiphos-methyl with bioresmethrin are suggested as grain protectants, subject to the necessary international approval of residues

The <i>M^.–M</i>_disk Relationship for Herbig Ae/Be Stars: A lifetime problem for disks with low masses?

The accretion of material from protoplanetary disks onto their central stars is a fundamental process in the evolution of these systems and a key diagnostic in constraining the disk lifetime. We analyze the relationship between the stellar accretion rate and the disk mass in 32 intermediate-mass Herbig Ae/Be systems and compare them to their lower-mass counterparts, T Tauri stars. We find that the M ̇-Mdisk relationship for Herbig Ae/Be stars is largely flat at ∼10−7 M☉ yr−1 over 3 orders of magnitude in dust mass. While most of the sample follows the T Tauri trend, a subset of objects with high accretion rates and low dust masses are identified. These outliers (12 out of 32 sources) have an inferred disk lifetime of less than 0.01 Myr and are dominated by objects with low infrared excess. This outlier sample is likely identified in part by the bias in classifying Herbig Ae/Be stars, which requires evidence of accretion that can only be reliably measured above a rate of ∼10−9M☉ yr−1 for these spectral types. If the disk masses are not underestimated and the accretion rates are not overestimated, this implies that these disks may be on the verge of dispersal, which may be due to efficient radial drift of material or outer disk depletion by photoevaporation and/or truncation by companions. This outlier sample likely represents a small subset of the larger young, intermediate-mass stellar population, the majority of which would have already stopped accreting and cleared their disks

Australian pharmacists' self-perceptions in relation to the 'Advanced Pharmacy Practice Framework'

Background: The Australian Pharmacy Practice Framework was developed by the Advanced Pharmacy Practice Steering Committee and endorsed by the Pharmacy Board of Australia in October 2012. The Steering Committee conducted a study that found practice portfolios to be the preferred method to assess and credential Advanced Pharmacy Practitioner, which is currently being piloted by the Australian Pharmacy Council. Credentialing is predicted to open to all pharmacists practising in Australia by November 2015

Puf3p induces translational repression of genes linked to oxidative stress

In response to stress, the translation of many mRNAs in yeast can change in a fashion discordant with the general repression of translation. Here, we use machine learning to mine the properties of these mRNAs to determine specific translation control signals. We find a strong association between transcripts acutely translationally repressed under oxidative stress and those associated with the RNA-binding protein Puf3p, a known regulator of cellular mRNAs encoding proteins targeted to mitochondria. Under oxidative stress, a PUF3 deleted strain exhibits more robust growth than wild-type cells and the shift in translation from polysomes to monosomes is attenuated, suggesting puf3Δ cells perceive less stress. In agreement, the ratio of reduced:oxidized glutathione, a major antioxidant and indicator of cellular redox state, is increased in unstressed puf3Δ cells but remains lower under stress. In untreated conditions, Puf3p migrates with polysomes rather than ribosome-free fractions, but this is lost under stress. Finally, reverse transcriptase-polymerase chain reaction (RT-PCR) of Puf3p targets following affinity purification shows Puf3p-mRNA associations are maintained or increased under oxidative stress. Collectively, these results point to Puf3p acting as a translational repressor in a manner exceeding the global translational response, possibly by temporarily limiting synthesis of new mitochondrial proteins as cells adapt to the stress

Bacterial expression of two human aryl sulfotransferases

The effect of replacing a single codon in the N-terminal of human aryl sulfotransferase (HAST) 1 and 3 with one that is more commonly found in E. coli genes was assessed. The pKK233-2 E. coli expression vector was employed and the polymerase chain reaction (PCR) was used to introduce the 5' nucleotide substitution, at the same time maintaining the fidelity of the amino acid sequence. The data indicates that this change had a minimal effect on protein production, subcellular localization or, in the case of HAST3, catalytic activity. In general, the pKK233-2 E. coli vector has been less than optimal for expressing human sulfotransferase cDNAs. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved

Archetypal transcriptional blocks underpin yeast gene regulation in response to changes in growth conditions

The transcriptional responses of yeast cells to diverse stresses typically include gene activation and repression. Specific stress defense, citric acid cycle and oxidative phosphorylation genes are activated, whereas protein synthesis genes are coordinately repressed. This view was achieved from comparative transcriptomic experiments delineating sets of genes whose expression greatly changed with specific stresses. Less attention has been paid to the biological significance of 1) consistent, albeit modest, changes in RNA levels across multiple conditions, and 2) the global gene expression correlations observed when comparing numerous genome-wide studies. To address this, we performed a meta-analysis of 1379 microarray-based experiments in yeast, and identified 1388 blocks of RNAs whose expression changes correlate across multiple and diverse conditions. Many of these blocks represent sets of functionally-related RNAs that act in a coordinated fashion under normal and stress conditions, and map to global cell defense and growth responses. Subsequently, we used the blocks to analyze novel RNA-seq experiments, demonstrating their utility and confirming the conclusions drawn from the meta-analysis. Our results provide a new framework for understanding the biological significance of changes in gene expression: ‘archetypal’ transcriptional blocks that are regulated in a concerted fashion in response to external stimuli

Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical <i>in vitro</i> tribological study

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus

The 4E-BP Caf20p Mediates Both eIF4E-Dependent and Independent Repression of Translation

Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5’cap. A family of binding proteins, termed the 4E-BPs, interact with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs, Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook global approaches to identify protein and RNA partners of both 4E-BPs by immunoprecipitation of tagged proteins combined with mass spectrometry or next-generation sequencing. Unexpectedly, mass spectrometry indicated that the 4E-BPs associate with many ribosomal proteins. 80S ribosome and polysome association was independently confirmed and was not dependent upon interaction with eIF4E, as mutated forms of both Caf20p and Eap1p with disrupted eIF4E-binding motifs retain ribosome interaction. Whole-cell proteomics revealed Caf20p mutations cause both up and down-regulation of proteins and that many changes were independent of the 4E-binding motif. Investigations into Caf20p mRNA targets by immunoprecipitation followed by RNA sequencing revealed a strong association between Caf20p and mRNAs involved in transcription and cell cycle processes, consistent with observed cell cycle phenotypes of mutant strains. A core set of over 500 Caf20p-interacting mRNAs comprised of both eIF4E-dependent (75%) and eIF4E-independent targets (25%), which differ in sequence attributes. eIF4E-independent mRNAs share a 3’ UTR motif. Caf20p binds all tested motif-containing 3’ UTRs. Caf20p and the 3’UTR combine to influence ERS1 mRNA polysome association consistent with Caf20p contributing to translational control. Finally ERS1 3’UTR confers Caf20-dependent repression of expression to a heterologous reporter gene. Taken together, these data reveal conserved features of eIF4E-dependent Caf20p mRNA targets and uncover a novel eIF4E-independent mode of Caf20p binding to mRNAs that extends the regulatory role of Caf20p in the mRNA-specific repression of protein synthesis beyond its interaction with eIF4E

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed