Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources

This is the final version. Available on open access from the American Society for Microbiology via the DOI in this recordData availability. The proteomic data set can be accessed in Table S1 at https://figshare.com/ articles/Membrane_receptors_contribute_to_activation_and_efficient_signaling_of_Mitogen-Activated _Protein_Kinase_cascades_during_adaptation_of_Aspergillus_fumigatus_to_different_stressors_and _carbon_sources/12402125The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p branch includes two other proteins, the Msb2p mucin and Opy2p. Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Here, we investigated the roles played by A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p putative homologues during the activation of the mitogen-activated protein kinase (MAPK) HOG pathway. The shoA, msbA, and opyA singly and doubly null mutants are important for the cell wall integrity (CWI) pathway, oxidative stress, and virulence as assessed by a Galleria mellonella model. Genetic interactions of ShoA, MsbA, and OpyA are also important for proper activation of the SakAHog1p and MpkASlt2 cascade and the response to osmotic and cell wall stresses. Comparative label-free quantitative proteomics analysis of the singly null mutants with the wild-type strain upon caspofungin exposure indicates that the absence of ShoA, MsbA, and OpyA affects the osmotic stress response, carbohydrate metabolism, and protein degradation. The putative receptor mutants showed altered trehalose and glycogen accumulation, suggesting a role for ShoA, MsbA, and OpyA in sugar storage. Protein kinase A activity was also decreased in these mutants. We also observed genetic interactions between SlnA, ShoA, MsbA, and OpyA, suggesting that both branches are important for activation of the HOG/CWI pathways. Our results help in the understanding of the activation and modulation of the HOG and CWI pathways in this important fungal pathogen.São Paulo Research Foundation (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Irish Research CouncilScience Foundation Irelan

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies

Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage

[EN] As a well established discipline and profession, project management has its distinctive tools and techniques. One of them that has been considered the embodiment of the core principles of project management is the Earned Value Management (EVM). In managing construction projects, the EVM has been considered as a suitable tool and hence, has been implemented in various construction industry but absent in some others. Taking into account the dynamic environment where construction companies have to operate, particularly in turbulence environments as the direct result of recent global economic downturn, this paper explores the potential implementation of EVM in one of the construction industry, the Spanish construction industry. The outcomes confirm the needs for and feasibility of implementing EVM as a structured approach in the industry to reposition the Spanish construction industry with the long term view to increase its project management maturity level as a pathway to gaining competitive advantage.Universitat Politecnica de Valencia [grant number 19701344]Sutrisna, M.; Pellicer, E.; Torres-Machí, C.; Picornell, M. (2018). Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage. International Journal of Construction Management. 20(1):1-12. https://doi.org/10.1080/15623599.2018.1459155S112201Anbari, F. T. (2004). Earned value project management method and extensions. IEEE Engineering Management Review, 32(3), 97-97. doi:10.1109/emr.2004.25113Aram, J. D., & Walochik, K. (1996). Improvisation and the Spanish Manager. International Studies of Management & Organization, 26(4), 73-89. doi:10.1080/00208825.1996.11656695Brandon, D. M. (1998). Implementing Earned Value Easily and Effectively. Project Management Journal, 29(2), 11-18. doi:10.1177/875697289802900204Brown, A., & Adams, J. (2000). Measuring the effect of project management on construction outputs: a new approach. International Journal of Project Management, 18(5), 327-335. doi:10.1016/s0263-7863(99)00026-5Bryde, D. J. (2003). Modelling project management performance. International Journal of Quality & Reliability Management, 20(2), 229-254. doi:10.1108/02656710310456635Chen, H. L., Chen, W. T., & Lin, Y. L. (2016). Earned value project management: Improving the predictive power of planned value. International Journal of Project Management, 34(1), 22-29. doi:10.1016/j.ijproman.2015.09.008De la Cruz, M. P., del Caño, A., & de la Cruz, E. (2006). Downside Risks in Construction Projects Developed by the Civil Service: The Case of Spain. Journal of Construction Engineering and Management, 132(8), 844-852. doi:10.1061/(asce)0733-9364(2006)132:8(844)Din, S., Abd-Hamid, Z., & Bryde, D. J. (2011). ISO 9000 certification and construction project performance: The Malaysian experience. International Journal of Project Management, 29(8), 1044-1056. doi:10.1016/j.ijproman.2010.11.001Eldin, N. N. (1989). Measurement of Work Progress: Quantitative Technique. Journal of Construction Engineering and Management, 115(3), 462-474. doi:10.1061/(asce)0733-9364(1989)115:3(462)Gidado, K. I. (1996). Project complexity: The focal point of construction production planning. Construction Management and Economics, 14(3), 213-225. doi:10.1080/014461996373476Hastak, M., Halpin, D. W., & Vanegas, J. (1996). COMPASS—New Paradigm for Project Cost Control Strategy and Planning. Journal of Construction Engineering and Management, 122(3), 254-264. doi:10.1061/(asce)0733-9364(1996)122:3(254)D. Holt, G., & S. Goulding, J. (2014). Conceptualisation of ambiguous-mixed-methods within building and construction research. Journal of Engineering, Design and Technology, 12(2), 244-262. doi:10.1108/jedt-02-2013-0020Ibbs, C. W., & Kwak, Y. H. (2000). Assessing Project Management Maturity. Project Management Journal, 31(1), 32-43. doi:10.1177/875697280003100106Jugdev, K., & Thomas, J. (2002). 2002 Student Paper Award Winner: Project Management Maturity Models: The Silver Bullets of Competitive Advantage? Project Management Journal, 33(4), 4-14. doi:10.1177/875697280203300402Kim, E., Wells, W. G., & Duffey, M. R. (2003). A model for effective implementation of Earned Value Management methodology. International Journal of Project Management, 21(5), 375-382. doi:10.1016/s0263-7863(02)00049-2Kim, T., Kim, Y.-W., & Cho, H. (2016). Customer Earned Value: Performance Indicator from Flow and Value Generation View. Journal of Management in Engineering, 32(1), 04015017. doi:10.1061/(asce)me.1943-5479.0000377Laufer, A., & Tucker, R. L. (1987). Is construction project planning really doing its job? A critical examination of focus, role and process. Construction Management and Economics, 5(3), 243-266. doi:10.1080/01446198700000023Liberatore, M. J., Pollack-Johnson, B., & Smith, C. A. (2001). Project Management in Construction: Software Use and Research Directions. Journal of Construction Engineering and Management, 127(2), 101-107. doi:10.1061/(asce)0733-9364(2001)127:2(101)Mir, F. A., & Pinnington, A. H. (2014). Exploring the value of project management: Linking Project Management Performance and Project Success. International Journal of Project Management, 32(2), 202-217. doi:10.1016/j.ijproman.2013.05.012Navon, R., & Haskaya, I. (2006). Is detailed progress monitoring possible without designated manual data collection? Construction Management and Economics, 24(12), 1225-1229. doi:10.1080/01446190600999097Onwuegbuzie, A. J., & Leech, N. L. (2005). Taking the «Q» Out of Research: Teaching Research Methodology Courses Without the Divide Between Quantitative and Qualitative Paradigms. Quality & Quantity, 39(3), 267-295. doi:10.1007/s11135-004-1670-0Oviedo-Haito, R. J., Jiménez, J., Cardoso, F. F., & Pellicer, E. (2014). Survival Factors for Subcontractors in Economic Downturns. Journal of Construction Engineering and Management, 140(3), 04013056. doi:10.1061/(asce)co.1943-7862.0000811Pellicer, E., Sanz, M. A., Esmaeili, B., & Molenaar, K. R. (2016). Exploration of Team Integration in Spanish Multifamily Residential Building Construction. Journal of Management in Engineering, 32(5), 05016012. doi:10.1061/(asce)me.1943-5479.0000438Potts, K., & Ankrah, N. (2008). Construction Cost Management. doi:10.4324/9780203933015Vanhoucke, M. (2012). Project Management with Dynamic Scheduling. doi:10.1007/978-3-642-25175-7Yazici, H. J. (2009). The Role of Project Management Maturity and Organizational Culture in Perceived Performance. Project Management Journal, 40(3), 14-33. doi:10.1002/pmj.20121Yu, A. G., Flett, P. D., & Bowers, J. A. (2005). Developing a value-centred proposal for assessing project success. International Journal of Project Management, 23(6), 428-436. doi:10.1016/j.ijproman.2005.01.00

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease – study protocol for a randomised controlled trial [ISRCTN11611768]

BACKGROUND: Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation. METHODS/DESIGN: We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12–15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out. DISCUSSION: Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice

Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua

Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 ± 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 ± 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis

Development of a core outcome set for orthodontic trials using a mixed-methods approach: Protocol for a multicentre study

© 2017 The Author(s). Background: Orthodontic treatment is commonly undertaken in young people, with over 40% of children in the UK needing treatment and currently one third having treatment, at a cost to the National Health Service in England and Wales of £273 million each year. Most current research about orthodontic care does not consider what patients truly feel about, or want, from treatment, and a diverse range of outcomes is being used with little consistency between studies. This study aims to address these problems, using established methodology to develop a core outcome set for use in future clinical trials of orthodontic interventions in children and young people. Methods/design: This is a mixed-methods study incorporating four distinct stages. The first stage will include a scoping review of the scientific literature to identify primary and secondary outcome measures that have been used in previous orthodontic clinical trials. The second stage will involve qualitative interviews and focus groups with orthodontic patients aged 10 to 16 years to determine what outcomes are important to them. The outcomes elicited from these two stages will inform the third stage of the study in which a long-list of outcomes will be ranked in terms of importance using electronic Delphi surveys involving clinicians and patients. The final stage of the study will involve face-to-face consensus meetings with all stakeholders to discuss and agree on the outcome measures that should be included in the final core outcome set. Discussion: This research will help to inform patients, parents, clinicians and commissioners about outcomes that are important to young people undergoing orthodontic treatment. Adoption of the core outcome set in future clinical trials of orthodontic treatment will make it easier for results to be compared, contrasted and combined. This should translate into improved decision-making by all stakeholders involved. Trial registration: The project has been registered on the Core Outcome Measures in Effectiveness Trials (COMET) website, January 2016

A strong conditional mutualism limits and enhances seed dispersal and germination of a tropical palm

Seed predation and seed dispersal can have strong effects on early life history stages of plants. These processes have often been studied as individual effects, but the degree to which their relative importance co-varies with seed predator abundance and how this influences seed germination rates is poorly understood. Therefore, we used a combination of observations and field experiments to determine the degree to which germination rates of the palm Astrocaryum mexicanum varied with abundance of a small mammal seed predator/disperser, Heteromysdesmarestianus, in a lowland tropical forest. Patterns of abundance of the two species were strongly related; density of H. desmarestianus was low in sites with low density of A. mexicanum and vice versa. Rates of predation and dispersal of A. mexicanum seeds depended on abundance of H. desmarestianus; sites with high densities of H. desmarestianus had the highest rates of seed predation and lowest rates of seed germination, but a greater total number of seeds were dispersed and there was greater density of seedlings, saplings, and adults of A. mexicanum in these sites. When abundance of H. desmarestianus was experimentally reduced, rates of seed predation decreased, but so did dispersal of A. mexicanum seeds. Critically, rates of germination of dispersed seeds were 5 times greater than undispersed seeds. The results suggest that the relationship between A. mexicanum and H. desmarestianus is a conditional mutualism that results in a strong local effect on the abundance of each species. However, the magnitude and direction of these effects are determined by the relative strength of opposing, but related, mechanisms. A. mexicanum nuts provide H. desmarestianus with a critical food resource, and while seed predation on A. mexicanum nuts by H. desmarestianus is very intense, A. mexicanum ultimately benefits because of the relatively high germination rates of its seeds that are dispersed by H. desmarestianus