Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote

The box jellyfish Chironex fleckeri is extremely venomous, and envenoming causes tissue necrosis, extreme pain and death within minutes after severe exposure. Despite rapid and potent venom action, basic mechanistic insight is lacking. Here we perform molecular dissection of a jellyfish venom-induced cell death pathway by screening for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis. We identify the peripheral membrane protein ATP2B1, a calcium transporting ATPase, as one host factor required for venom cytotoxicity. Targeting ATP2B1 prevents venom action and confers long lasting protection. Informatics analysis of host genes required for venom cytotoxicity reveal pathways not previously implicated in cell death. We also discover a venom antidote that functions up to 15 minutes after exposure and suppresses tissue necrosis and pain in mice. These results highlight the power of whole genome CRISPR screening to investigate venom mechanisms of action and to rapidly identify new medicines

Group A Streptococcus M1T1 Intracellular Infection of Primary Tonsil Epithelial Cells Dampens Levels of Secreted IL-8 Through the Action of SpyCEP.

Streptococcus pyogenes (Group A Streptococcus; GAS) commonly causes pharyngitis in children and adults, with severe invasive disease and immune sequelae being an infrequent consequence. The ability of GAS to invade the host and establish infection likely involves subversion of host immune defenses. However, the signaling pathways and innate immune responses of epithelial cells to GAS are not well-understood. In this study, we utilized RNAseq to characterize the inflammatory responses of primary human tonsil epithelial (TEpi) cells to infection with the laboratory-adapted M6 strain JRS4 and the M1T1 clinical isolate 5448. Both strains induced the expression of genes encoding a wide range of inflammatory mediators, including IL-8. Pathway analysis revealed differentially expressed genes between mock and JRS4- or 5448-infected TEpi cells were enriched in transcription factor networks that regulate IL-8 expression, such as AP-1, ATF-2, and NFAT. While JRS4 infection resulted in high levels of secreted IL-8, 5448 infection did not, suggesting that 5448 may post-transcriptionally dampen IL-8 production. Infection with 5448ΔcepA, an isogenic mutant lacking the IL-8 protease SpyCEP, resulted in IL-8 secretion levels comparable to JRS4 infection. Complementation of 5448ΔcepA and JRS4 with a plasmid encoding 5448-derived SpyCEP significantly reduced IL-8 secretion by TEpi cells. Our results suggest that intracellular infection with the pathogenic GAS M1T1 clone induces a strong pro-inflammatory response in primary tonsil epithelial cells, but modulates this host response by selectively degrading the neutrophil-recruiting chemokine IL-8 to benefit infection

Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence 672ATEF2QQ677, consistent with a cleavage motif resembling S/T-X-F2XD/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1P146-F3P146 that mimic P50P146, P40P146, and P85P146 were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3P146 generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography

Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus

A recent analysis of group A Streptococcus (GAS) invasive infections in Australia has shown a predominance of M4 GAS, a serotype recently reported to lack the antiphagocytic hyaluronic acid (HA) capsule. Here, we use molecular genetics and bioinformatics techniques to characterize 17 clinical M4 isolates associated with invasive disease in children during this recent epidemiology. All M4 isolates lacked HA capsule, and whole genome sequence analysis of two isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Conversely, M4 isolates possess a functional HA-degrading hyaluronate lyase (HylA) enzyme that is rendered nonfunctional in other GAS through a point mutation. Transformation with a plasmid expressing hasABC restored partial encapsulation in wild-type (WT) M4 GAS, and full encapsulation in an isogenic M4 mutant lacking HylA. However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection. Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition. These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

Crop Updates 2002 - Cereals

This session covers thirty one papers from different authors: VARIETIES AND BREEDING 1. Agronomic evaluation of wheat and barley in the central wheatbelt of Western Australia, Peter Burgess1and Gary Fawell2, 1Agritech and 2Farmanco Management 2. Evaluating stress tolerance to terminal drought by Western Australian wheats, Dean Diepeveen and Dr Tim Setter, Department of Agriculture 3. Broadscale wheat variety comparisons featuring Wyalkatchem, Jeff Russell, Department of Agriculture 4. Australian crop accreditation system variety selector, Tony Seymour, Australian Crop Accreditation System 5. Future wheat varieties, Robin Wilson, Iain Barclay,Robyn McLean, Robert Loughman, Jenny Garlinge, Bill Lambe, Neil Venn and Peter Clarke, Department of Agriculture AGRONOMY 6. Beware of wheat variety interactions with row spacing and seed rate, Mohammad Amjad and Wal Anderson, Department of Agriculture 7. Yield and falling numbers of wheat varieties on the South Coast, Mohammad Amjad and Wal Anderson, Department of Agriculture 8. Maximising wheat variety performance through agronomic management, Wal Anderson, Raffaele Del Cima, James Bee, Darshan Sharma, Sheena Lyon, Melaine Kupsch, Mohammad Amjad, Pam Burgess, Veronika Reck, Brenda Shackley, Ray Tugwell, BindiWebb and Steve Penny Jr, Department of Agriculture 9. High impact of soil type and seasonal rainfall on optimum wheat seed rate , Raffaele Del Cima and Wal Anderson Department of Agriculture 10. 101 seasons in one day: Using the ‘WA Wheat’ database to predict wheat yield, James Fisher1, Bill Bowden1, Craig Scanlan1, Senthold Asseng2and Michael Robertson2 1Department of Agriculture, 2CSIRO 11. Economics of improving compact soils, M.A. Hamza1, G. McConnell2and W.K. Anderson1, 1Department of Agriculture, 2Planfarm 12. Reducing the risks in producing durum wheat in Western Australia, Md Shahajahan Miyan and Wal Anderson, Department of Agriculture 13. Taking the Why out of Wyalkatchem – the new widely adopted wheat variety, Steve Penny, Department of Agriculture 14. Influence of nutrition and environmental factors on seed vigour in wheat, Darshan Sharma, Wal Anderson and Daya Patabendige, Department of Agriculture NUTRITION 15. N and K are important for oat yield and quality, Patrick Gethin, Stephen Loss, Tim O’Dea, Ryan Guthrie and Lisa Leaver, CSBP Futurefarm 16. Effects of nitrogen and phosphorus on the grain yield and quality of noodle wheat, Tyrone Henning1, Lionel Martin1and Wal Anderson2 1Muresk Institute of Agriculture, 2Department of Agriculture 17. Assessment of a high input fertiliser regime on the yield and quality of Gairdner barley, Narelle Hill1, Simon Wallwork2and Laurence Carslake2 1Department of Agriculture, 2Wesfarmers Landmark 18. The use of Flexi-N to achieve high yielding, high protein wheat, Darren Hughes1, Lionel Martin1, Wal Anderson2and Stephen Loss3 1Muresk Institute of Agriculture, 2Department of Agriculture, 3CSBP Futurefarm 19. Are liquid phosphorus fertilisers more efficient than solid fertilisers in Western Australia?Stephen Loss, Lisa Leaver, Ryan Guthrie, Patrick Gethin and Tim O’Dea, CSBP Futurefarm 20. Oats respond to phosphorus and potassium, Glenn McDonald, Department of Agriculture PESTS AND DISEASES 21. Cereal disease diagnostics and rust monitoring, Nichole Burges and Dominie Wright, Department of Agriculture 22. Distribution and incidence of aphids and barley yellow dwarf virus in over-summering grasses in the Western Australian wheatbelt, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Department of Agriculture 23. Spring sprays for powdery mildew control in cereals, Kith Jayasena1, Kazue Tanaka1, Vanessa Johnson1, Robert Loughman1and Josh Jury2 1Department of Agriculture, 2Wesfarmers Landmark 24. Impact of root lesion nematodes on wheat and triticale in Western Australia, Sean Kelly and Shashi Sharma, Department of Agriculture 25. Cropping options for the management of root lesion nematodes in Western Australia, Sean Kelly, Shashi Sharma and Robert Loughman, Department of Agriculture 26. Cereal rust update 2002 – new stem rust on Camm wheat, Robert Loughman1and Robert Park2 1Department of Agriculture, 2University of Sydney 27. Cereal aphids and direct feeding damage to cereals, Phil Michael, Department of Agriculture 28. A decision support system for control of aphids and BYDV in cereal crops, Debbie Thackray, Jenny Hawkes and Roger Jones, Department of Agriculture and Centre for Legumes in Mediterranean Agriculture STORAGE 29. Aeration – opportunity for profit, Christopher Newman, Department of Agriculture CLIMATE 30. Financial impact of frost on the Western Australian grains industry, Garren Knell and Kim Povey, ConsultAg 31. Summary of 2001 weather and seasonal prospects for 2002, David Stephens, Department of Agricultur

The accessibility and acceptability of self-management support interventions for men with long term conditions: a systematic review and meta-synthesis of qualitative studies

Background: Self-management support interventions can improve health outcomes, but their impact is limited by the numbers of people able or willing to access them. Men’s attendance at existing self-management support services appears suboptimal despite their increased risk of developing many of the most serious long term conditions. The aim of this review was to determine whether current self-management support interventions are acceptable and accessible to men with long term conditions, and explore what may act as facilitators and barriers to access of interventions and support activities. Methods: A systematic search for qualitative research was undertaken on CINAHL, EMBASE, MEDLINE, PsycINFO and Social Science Citation Index, in July 2013. Reference lists of relevant articles were also examined. Studies that used a qualitative design to explore men’s experiences of, or perceptions towards, self-management support for one or more long term condition were included. Studies which focused on experiences of living with a long term condition without consideration of self-management support were excluded. Thirty-eight studies met the inclusion criteria. A meta-ethnography approach was employed to synthesise the findings. Results: Four constructs associated with men’s experience of, and perceptions towards, self management support were identified: 1) need for purpose; 2) trusted environments; 3) value of peers; and 4) becoming an expert. The synthesis showed that men may feel less comfortable participating in self-management support if it is viewed as incongruous with valued aspects of their identity, particularly when activities are perceived to challenge masculine ideals associated with independence, stoicism, and control. Men may find self-management support more attractive when it is perceived as action-oriented, having a clear purpose, and offering personally meaningful information and practical strategies that can be integrated into daily life. Conclusions: Self-management support is most likely to be successful in engaging men when it is congruent with key aspects of their masculine identity. In order to overcome barriers to access and fully engage with interventions, some men may need self-management support interventions to be delivered in an environment that offers a sense of shared understanding, connectedness, and normality, and involves and/or is facilitated by men with a shared illness experience

Sediment source fingerprinting: benchmarking recent outputs, remaining challenges and emerging themes

Abstract: Purpose: This review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science. Methods: Web of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017. Scope: Areas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing. Conclusions: The popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach