Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule

Cryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101Δ mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101Δ strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101Δ mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host-relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions

Species-Specific Effects of Passive Warming in an Antarctic Moss System

Polar systems are experiencing rapid climate change and the high sensitivity of these Arctic and Antarctic ecosystems make them especially vulnerable to accelerated ecological transformation. In Antarctica, warming results in a mosaic of ice-free terrestrial habitats dominated by a diverse assemblage of cryptogamic plants (i.e. mosses and lichens). Although these plants provide key habitat for a wide array of microorganisms and invertebrates, we have little understanding of the interaction between trophic levels in this terrestrial ecosystem and whether there are functional effects of plant species on higher trophic levels that may alter with warming. Here, we used open top chambers on Fildes Peninsula, King George Island, Antarctica, to examine the effects of passive warming and moss species on the abiotic environment and ultimately on higher trophic levels. For the dominant mosses, Polytrichastrum alpinum and Sanionia georgicouncinata, we found species-specific effects on the abiotic environment, including moss canopy temperature and soil moisture. In addition, we found distinct shifts in sexual expression in P. alpinum plants under warming compared to mosses without warming, and invertebrate communities in this moss species were strongly correlated with plant reproduction. Mosses under warming had substantially larger total invertebrate communities, and some invertebrate taxa were influenced differentially by moss species. However, warmed moss plants showed lower fungal biomass than control moss plants, and fungal biomass differed between moss species. Our results indicate that continued warming may impact the reproductive output of Antarctic moss species, potentially altering terrestrial ecosystems dynamics from the bottom up. Understanding these effects requires clarifying the foundational, mechanistic role that individual plant species play in mediating complex interactions in Antarctica\u27s terrestrial food webs

Working conditions, work-life conflict and wellbeing in UK prison officers: the role of affective rumination and detachment

Although prison officers experience the working conditions associated with work-life conflict, little research has explored this issue. This study draws upon the work-home resources model (ten Brummelhuis & Bakker, 2012) to investigate relationships between working conditions (demands and experiences of aggression) and time-based, strain-based and behavior-based work-life conflict in UK prison officers (n = 1,682). Associations between working conditions, work-life conflict, and emotional exhaustion were also examined. Two recovery behaviors (affective rumination and detachment) were considered as potential moderators of associations between working conditions and emotional exhaustion. High levels of all work-life conflict dimensions were found which were related to working conditions and emotional exhaustion. Some evidence was found that higher rumination and lower detachment exacerbated the positive association between both job demands and aggression and emotional exhaustion. The implications of the findings for the wellbeing and professional functioning of prison officers are discussed, together with key areas for future research

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Crop Updates 2001 - Lupins

This session covers twenty six papers from different authors: INTRODUCTION, 1. Introduction, Dr Mark Sweetingham LUPIN RESEARCH AND INDUSTRY DEVELOPMENT, Agriculture Western Australia VARIETIES 2. Lupin variety performance: Are you making the most of it? Bevan J. Buirchell, Agriculture Western Australia 3. Adaption of restricted-branching lupins in Western Australia, Bob French and Laurie Wahlsten, Agriculture Western Australia 4. Isolated microspore culture of lupin for production of doubled haploids, Dr Janet Wroth, Dr Kirsty Bayliss and A/Prof. Wallace Cowling, Plant Sciences, Faculty of Agriculture, The University of Western Australia NUTRITION 5. Banding manganese fertiliser below the seed increases seed yields of narrow-leafed lupins, R.F. Brennan, Agriculture Western Australia 6. Residual value of manganese fertiliser for lupin grain production, R.F. Brennan, Agriculture Western Australia AGRONOMY 7. Lupin seeding density, Miles Dracup, Agriculture Western Australia, Nick Galwey, University of Western Australia and Bob Thomson, University of Western AustraliaPESTS AND DISEASES 8. Anthracnose in lupins – understanding the risk, Moin Salam, Art Diggle, Geoff Thomas, Mark Sweetinghamand Bill O’Neill, Agriculture Western Australia 9. Implications of the ‘green bridge’ for viral and fungal disease carry-over between seasons, Debbie Thackray, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 10. Insect pest development in WA via the ‘green bridge’, Kevin Walden, Agriculture Western Australia 11. Lupin anthracnose – seed infection thresholds, Geoff Thomas, Agriculture Western Australia 12. Identification and characterisation of resistance genes to Phomopsis blight in narrow-leafed lupin, M. Shankar1, M.W. Sweetingham1&2 and W.A. Cowling1&3 , 1Co-operative Research Centre for Legumes in Mediterranean Agriculture, 2Agriculture Western Australia, 3Plant Sciences 13. Plant disease diagnostics, Dominie Wright and Nichole Burges, Agriculture Western Australia 14. Detection of strains of Phomopsis exhibiting species preference in lupins, M. Shankar, 1Co-operative Research Centre for Legumes in Mediterranean Agriculture and M.W. Sweetingham, Agriculture Western Australia 15. Potential alternate host for the lupin anthracnose pathogen, Geoff Thomasa, Hu’aan Yangb, Mark Sweetinghamab and Ming Pei Youa, aAgriculture Western Australia, bCooperative Research Centre for Legumes in Mediterranean Agriculture WEEDS 16. Wild radish – the implications for our rotations, Dr David Bowran, Centre for Cropping Systems 17. Competitiveness of wild radish in a wheat – lupin rotation, Abul Hashem, Nerys Wilkins, and Terry Piper, Agriculture Western Australia 18. Population explosion and persistence of wild radish in a wheat-lupin rotation, Abul Hashem, Nerys Wilkins, Aik Cheam and Terry Piper, Agriculture Western Australia 19. Inter-row knockdowns for profitable lupins, Paul Blackwell, Agriculture Western Australia, Miles Obst, Mingenew 20. Is it safe to use 2,4-D Ester 80% pre-sowing when furrow sowing lupins? Andrew Sandison, Elders Ltd QUALITY AND MARKET DEVELOPMENT 21. Lupin protein – what we know, Bill O’Neill, Agriculture Western Australia 22. Foliar N application increases grain protein in lupins, Bob French and Laurie Wahlsten, Agriculture Western Australia 23. Can lupin grain protein be increased with Flexi-N? Cameron Weeks, Erin Hasson, Mingenew-Irwin Group and Luigi Moreschi, CSBP futurefarm 24. Putting a value on lupin use in the aquaculture industry: a fishy business? Brett D. Glencross, Fisheries WA, Fremantle Maritime Centre, Fremantle 25. Selection for thinner seed coats and pod walls in lupins, Jon Clements, Centre for Legumes in Mediterranean Agriculture and Miles Dracup, Agriculture Western Australia 26. Assessing the nutritional benefit of Australian sweet lupin (Lupinus angustifolius) in human foods, Ramon Hall (SPIRT PhD scholar), Stuart Johnson, Madeleine Ball, Deakin University, Melbourne, Sofia Sipsas and David Petterson, Agriculture Western Australi

An Age-Structured Extension to the Vectorial Capacity Model

Vectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention.Based on survival analysis we derived new equations for vectorial capacity and R(0) that are valid for any pattern of age-dependent (or age-independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies.Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0) was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0) is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R(0) ∼ 1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the paucity of data characterizing vector mortality patterns, particularly for free ranging vectors in the field

Operational research to inform a sub-national surveillance intervention for malaria elimination in Solomon Islands

Background: Successful reduction of malaria transmission to very low levels has made Isabel Province, Solomon Islands, a target for early elimination by 2014. High malaria transmission in neighbouring provinces and the potential for local asymptomatic infections to cause malaria resurgence highlights the need for sub-national tailoring of surveillance interventions. This study contributes to a situational analysis of malaria in Isabel Province to inform an appropriate surveillance intervention. Methods. A mixed method study was carried out in Isabel Province in late 2009 and early 2010. The quantitative component was a population-based prevalence survey of 8,554 people from 129 villages, which were selected using a spatially stratified sampling approach to achieve uniform geographical coverage of populated areas. Diagnosis was initially based on Giemsa-stained blood slides followed by molecular analysis using polymerase chain reaction (PCR). Local perceptions and practices related to management of fever and treatment-seeking that would impact a surveillance intervention were also explored using qualitative research methods. Results: Approximately 33% (8,554/26,221) of the population of Isabel Province participated in the survey. Only one subject was found to be infected with Plasmodium falciparum (Pf) (96 parasites/L) using Giemsa-stained blood films, giving a prevalence of 0.01%. PCR analysis detected a further 13 cases, giving an estimated malaria prevalence of 0.51%. There was a wide geographical distribution of infected subjects. None reported having travelled outside Isabel Province in the previous three months suggesting low-level indigenous malaria transmission. The qualitative findings provide warning signs that the current community vigilance approach to surveillance will not be sufficient to achieve elimination. In addition, fever severity is being used by individuals as an indicator for malaria and a trigger for timely treatment-seeking and case reporting. In light of the finding of a low prevalence of parasitaemia, the current surveillance system may not be able to detect and prevent malaria resurgence. Conclusion: An adaption to the malERA surveillance framework is proposed and recommendations made for a tailored provincial-level surveillance intervention, which will be essential to achieve elimination, and to maintain this status while the rest of the country catches up

Using serological measures to monitor changes in malaria transmission in Vanuatu

BACKGROUND: With renewed interest in malaria elimination, island environments present unique opportunities to achieve this goal. However, as transmission decreases, monitoring and evaluation programmes need increasingly sensitive tools to assess Plasmodium falciparum and Plasmodium vivax exposure. In 2009, to assess the role of serological markers in evaluating malaria transmission, a cross-sectional seroprevalence study was carried out in Tanna and Aneityum, two of the southernmost islands of the Vanuatu archipelago, areas where malaria transmission has been variably reduced over the past few decades. METHODS: Malaria transmission was assessed using serological markers for exposure to P. falciparum and P. vivax. Filter blood spot papers were collected from 1,249 people from Tanna, and 517 people from Aneityum to assess the prevalence of antibodies to two P. falciparum antigens (MSP-119 and AMA-1) and two P. vivax antigens (MSP-119 and AMA-1). Age-specific prevalence was modelled using a simple catalytic conversion model based on maximum likelihood to generate a community seroconversion rate (SCR). RESULTS: Overall seropositivity in Tanna was 9.4%, 12.4% and 16.6% to P. falciparum MSP-119, AMA-1 and Schizont Extract respectively and 12.6% and 15.0% to P. vivax MSP-119 and AMA-1 respectively. Serological results distinguished between areas of differential dominance of either P. vivax or P. falciparum and analysis of age-stratified results showed a step in seroprevalence occurring approximately 30 years ago on both islands, indicative of a change in transmission intensity at this time. Results from Aneityum suggest that several children may have been exposed to malaria since the 2002 P. vivax epidemic. CONCLUSION: Seroepidemiology can provide key information on malaria transmission for control programmes, when parasite rates are low. As Vanuatu moves closer to malaria elimination, monitoring changes in transmission intensity and identification of residual malaria foci is paramount in order to concentrate intervention efforts