Bayesian Geostatistical Analysis and Ecoclimatic Determinants of Corynebacterium pseudotuberculosis Infection among Horses

Citation: Boysen, C., Davis, E. G., Beard, L. A., Lubbers, B. V., & Raghavan, R. K. (2015). Bayesian Geostatistical Analysis and Ecoclimatic Determinants of Corynebacterium pseudotuberculosis Infection among Horses. Plos One, 10(10), 15. doi:10.1371/journal.pone.0140666Kansas witnessed an unprecedented outbreak in Corynebacterium pseudotuberculosis infection among horses, a disease commonly referred to as pigeon fever during fall 2012. Bayesian geostatistical models were developed to identify key environmental and climatic risk factors associated with C. pseudotuberculosis infection in horses. Positive infection status among horses (cases) was determined by positive test results for characteristic abscess formation, positive bacterial culture on purulent material obtained from a lanced abscess (n = 82), or positive serologic evidence of exposure to organism (>= 1:512)(n = 11). Horses negative for these tests (n = 172)(controls) were considered free of infection. Information pertaining to horse demographics and stabled location were obtained through review of medical records and/or contact with horse owners via telephone. Covariate information for environmental and climatic determinants were obtained from USDA (soil attributes), USGS (land use/land cover), and NASA MODIS and NASA Prediction of Worldwide Renewable Resources (climate). Candidate covariates were screened using univariate regression models followed by Bayesian geostatistical models with and without covariates. The best performing model indicated a protective effect for higher soil moisture content (OR = 0.53, 95% CrI = 0.25, 0.71), and detrimental effects for higher land surface temperature (>= 35 degrees C) (OR = 2.81, 95% CrI = 2.21, 3.85) and habitat fragmentation (OR = 1.31, 95% CrI = 1.27, 2.22) for C. pseudotuberculosis infection status in horses, while age, gender and breed had no effect. Preventative and ecoclimatic significance of these findings are discussed

To My Daughter

<p>Equal numbers of macaque CD34⁺ cells were transduced in 3-d transduction cultures with either the HOXB4GFP or YFP vector and then cultured for an additional 9 d (T02266) or 6 d (K03290 and J02152) in the presence of SCF, TPO, Flt-3L, and G-CSF. All the transduced and expanded cells were infused into myeloablated animals. The percentage of HOXB4GFP⁺ and YFP⁺ granulocytes was assessed by flow cytometry. Shown is the engraftment of HOXB4GFP⁺ and YFP⁺ granulocytes after transplantation. (A) T02266, (B) K03290, and (C) J02152. </p

Novel reporter systems for facile evaluation of I-SceI-mediated genome editing

Two major limitations to achieve efficient homing endonuclease-stimulated gene correction using retroviral vectors are low frequency of gene targeting and random integration of the targeting vectors. To overcome these issues, we developed a reporter system for quick and facile testing of novel strategies to promote the selection of cells that undergo targeted gene repair and to minimize the persistence of random integrations and non-homologous end-joining events. In this system, the gene target has an I-SceI site upstream of an EGFP reporter; and the repair template includes a non-functional EGFP gene, the positive selection transgene MGMTP140K tagged with mCherry, and the inducible Caspase-9 suicide gene. Using this dual fluorescent reporter system it is possible to detect properly targeted integration. Furthermore, this reporter system provides an efficient approach to enrich for gene correction events and to deplete events produced by random integration. We have also developed a second reporter system containing MGMTP140K in the integrated target locus, which allows for selection of primary cells with the integrated gene target after transplantation. This system is particularly useful for testing repair strategies in primary hematopoietic stem cells. Thus, our reporter systems should allow for more efficient gene correction with less unwanted off target effects

Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells

BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])–transduced and expanded CD34 (+) cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6–9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene–expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS: These data demonstrate that HOXB4 overexpression in CD34 (+) cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available

Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands

BACKGROUND: The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections. METHODS: In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months. RESULTS: RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections. CONCLUSION: RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied

Finding meaning: HIV self-management and wellbeing among people taking antiretroviral therapy in Uganda

© 2016 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited. The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's selfmanagement of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resourcelimited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': They saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other nonmedical aspects of wellbeing for self-management which ART programmes might explore further and encourage

Crop Updates 2005 - Katanning

This session covers twenty five papers from different authors KEYNOTE How Farmers Can Work Together for a More Sustainable and Profitable Business, Brian McAlpine Farmer, Nuffield Scholar GENERAL 2005 Seasonal Outlook, David Stephens and Nicola Telcik, Department of Agriculture Essentials for cereal leaf disease management, K. Jayasena, R. Loughman, G. Thomas, C. Beard, and B. Paynter, Department of Agriculture Benefits to the grower of grain licensing, Colin Mann, Grain Licensing Authority SOIL & NUTRIENTS The effect of higher nitrogen fertiliser prices on rotation and fertiliser strategies in cropping systems, Ross Kingwell, Department of Agriculture Effect of stubble burning and seasonality on microbial processes and nutrient cycling, Francis Hoyle, University of Western Australia Soil Biology and Crop Production in Western Australian Farming Systems, D.V. Murphy, N. Milton, M. Osman, F.C. Hoyle, L.K Abbott, W.R. Cookson and S. Darmawanto, University of Western Australia Nutrient Management to get optimal production, Bill Bowden, Department of Agriculture OTHER CROPS Which malting barley variety and why? Blakely Paynter, Department of Agriculture KASPA AND OTHER NEW PULSE VARIETIES, 1. New Pulse varieties and where they fit in, K. Regan, P. White, Department of Agriculture & CLIMA, K. Siddique, CLIMA, K. Adhikari, Department of Agriculture & CLIMA, M. Harries, CLIMA Kaspa in the WA Grain Belt 2003-2004, Ian Pritchard, Department of Agriculture New annual pastures for Mediterranean farming systems, Angelo Loi, Phil Nichols, Clinton Revell & David Ferris, Department of Agriculture Challenging herbicide resistant ryegrass, Bill Roy, Agricultural Consulting & Research Services Pty.Ltd WEED MANAGEMENT Ingest, incinerate or invert? The pro’s and con’s of 3 weed seed removal tactics, Sally Peltzer1, Dave Minkey1 and Michael Walsh2 Department of Agriculture 1 and Western Australian Herbicide Resistance lnitiative2 A good use guide for pre-emergent herbicides, Alexandra Douglas, Department of Agriculture OTHER USEFUL INFORMATION 17.Growing season outlook, Meredith Fairbanks, Ian Foster, Geraldine Pasqual, David Stephens, Nicola Telcik, David Tennant, Department of Agriculture 18. Status Of Department Of Agriculture Western Australia Crop Varieties 19. Seed Licensee Details 20. Gene technology for growers. What is it? How does it Work? Belinda Barr, Australian Centre for Plant Functional Genomics, Dr Heather Bray, Molecular Plant Breeding Cooperative Research Centre. 21. Agronomic package for EGA Eagle Rock, Steve Penny, Department of Agriculture 22. Nutrient timing and requirements for increased crop yields in the high rainfall cropping zone, Narelle Hill, Ron McTaggart, Dr. Wal Anderson and Ray Tugwell Department of Agriculture 23. Insect contamination of cereal grain at harvest, Svetlana Micic and Phil Michael, Department of Agriculture 24. Crop leftovers: what’s in stubble for sheep? Roy Butler and Keith Croker, Department of Agriculture 25. Mandelup – Narrow-leafed lupi

microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.

Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)-gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients