95 research outputs found
Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes
No full textBackground
Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with 24,072 gene probe sets representing more than 23,000 gene transcripts.
Results
Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of gene transcripts showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity® Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group.
Conclusions
This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.This work was supported by Investigator Grants from Science Foundation Ireland (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038), a Research Stimulus Grant from the Department of Agriculture, Fisheries and Food (No: RSF 06 405) and a European Union Framework 7 Project Grant (No: KBBE-211602-MACROSYS). KEK is supported by the Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and Systems Biology PhD Programme http://bioinfo-casl.ucd.ie/PhD
International Quality-Controlled Ocean Database (IQuOD) v0.1: the temperature uncertainty specification
No full text© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cowley, R., Killick, R. E., Boyer, T., Gouretski, V., Reseghetti, F., Kizu, S., Palmer, M. D., Cheng, L., Storto, A., Le Menn, M., Simoncelli, S., Macdonald, A. M., & Domingues, C. M. International Quality-Controlled Ocean Database (IQuOD) v0.1: the temperature uncertainty specification. Frontiers in Marine Science, 8, (2021): 689695, https://doi.org/10.3389/fmars.2021.689695.Ocean temperature observations are crucial for a host of climate research and forecasting activities, such as climate monitoring, ocean reanalysis and state estimation, seasonal-to-decadal forecasts, and ocean forecasting. For all of these applications, it is crucial to understand the uncertainty attached to each of the observations, accounting for changes in instrument technology and observing practices over time. Here, we describe the rationale behind the uncertainty specification provided for all in situ ocean temperature observations in the International Quality-controlled Ocean Database (IQuOD) v0.1, a value-added data product served alongside the World Ocean Database (WOD). We collected information from manufacturer specifications and other publications, providing the end user with uncertainty estimates based mainly on instrument type, along with extant auxiliary information such as calibration and collection method. The provision of a consistent set of observation uncertainties will provide a more complete understanding of historical ocean observations used to examine the changing environment. Moving forward, IQuOD will continue to work with the ocean observation, data assimilation and ocean climate communities to further refine uncertainty quantification. We encourage submissions of metadata and information about historical practices to the IQuOD project and WOD.This work was supported by the Scientific Committee on Oceanic Research (SCOR) Working Group 148, funded by national SCOR committees and a grant to SCOR from the U.S. National Science Foundation (Grant OCE-1546580); and the Intergovernmental Oceanographic Commission of UNESCO/International Oceanographic Data and Information Exchange (IOC/IODE) IQuOD Steering Group. RC was supported through funding from the Earth Systems and Climate Change Hub of the Australian Government's National Environmental Science Program. RK and MP were supported by the Met Office Hadley Centre Climate Programme funded by BEIS and Defra. CD was supported by the Australian Research Council (Discovery Grant DP160103130), ARC Centre of Excellence for Climate Extremes (CE170100023) and by the Natural Environment Research Council (TICTOC, NE/P019293/1). AM's contribution was supported by National Science Foundation grant OCE#-1923387 and National Oceanographic and Atmospheric Administration grant #NA16OAR4310172
Taxation of financial assets in developing countries
No full textIn developing countries, most financial assets in formal markets are deposits at financial institutions. This potentially important tax base could be taxed at a low administrative cost. When revenues of financial taxes are significant, implicit taxes dwarf explicit taxes. The author focuses on the implicit taxation of financial assets through seigniorage, reserve requirements, lending targets, and interest ceilings combined with inflation. The last instrument has often been overlooked, but it has generated more than a third of implicit revenues in some cases by lowering the cost of government borrowing. Tax revenues are difficult to measure because of regulations that prevent the use of market prices for computation and distort the meaning of some definitions. For some countries, the standard method of seigniorage grossly underestimates the revenue from financial taxation. The author discusses various sources of distortion but ignores potential impacts on the level of saving and the growth rate. Although taxes on financial assets have a low administrative cost, the excess burden that stems from the misallocation of resources is probably a much higher fraction of revenues than that of other taxes.Economic Theory&Research,Environmental Economics&Policies,Banks&Banking Reform,Public Sector Economics&Finance,Municipal Financial Management
There is no dose-response relationship between the amount of exercise and improvement in HbA1c in interventions over 12 weeks in patients with type II diabetes : a meta-analysis and meta-regression
No full textBackground: Aerobic exercise is well recognised as an effective treatment for people with type 2 diabetes but the optimal amount of aerobic exercise to improve glycaemic control remains to be determined. Thus, a meta-analysis and meta-regression were carried out to assess this. Methods: Medline, Cochrane, Embase, and Web of Science databases were searched up until 15th December 2020 for the terms “aerobic exercise AND glycaemic control”, “type 2 diabetes AND exercise”, and “exercise AND glycaemic control AND Type 2 diabetes AND randomised control trial”. We included (i) randomised control trials of ≥12 weeks, (ii) trials where participants had type 2 diabetes and were aged 18 or over, (iii) the trial reported HbA1c concentrations pre- and post-intervention. Two reviewers selected studies and extracted data. Data are reported as standardized mean difference (SMD) and publication bias was assessed using funnel plots. Results: 5364 original titles were identified. 16 studies were included in the metaanalysis. Aerobic exercise reduced HbA1c vs. control (SMD = 0.56 (95% CI 0.3 – 0.82), p 0.05). Conclusion: 12-week or longer aerobic exercise programmes improve glycaemic control, and BMI in adults with type 2 diabetes. Longer or more intense interventions appear to confer no additional benefit on HbA1c
Administrative valuation of Soviet agricultural land : results using Lithuanian production data
No full textNew land tenure arrangements in the USSR require that agricultural producers pay for land use. The current distorted pricing system and the absence of functioning land markets complicate land valuation, and slow the adoption of new property relations. In a market economy that functions well, agricultural land would earn its approximate marginal value product in agricultural production. This value can be measured empirically from production data and can serve as an appropriate initial value for users'fees. The author estimates marginal value products for land for 1,032 collective and state farms in Lithuania using farm-level data for 1986 and 1987 and compares the marginal value products derived from actual received producer prices with those derived from border prices with alternative assumed exchange rates for the ruble.Environmental Economics&Policies,Economic Theory&Research,Markets and Market Access,Access to Markets,Agricultural Knowledge&Information Systems
Evaluation of a mass distribution programme for fine-mesh impregnated bednets against visceral leishmaniasis in eastern Sudan.
No full textDuring an epidemic of visceral leishmaniasis (VL) in eastern Sudan, Médecins Sans Frontières distributed 357,000 insecticide-treated bednets (ITN) to 155 affected villages between May 1999 and March 2001. To estimate the protective effect of the ITN, we evaluated coverage and use of ITN, and analysed VL incidence by village from March 1996 to June 2002. We provided ITN to 94% of the individuals >5 years old. Two years later, 44% (95% CI 39-48%) of nets were reasonably intact. Because ITN were mainly used as protection against nuisance mosquitoes, bednet use during the VL transmission season ranged from <10% during the hot dry months to 55% during the beginning of the rainy season. ITN were put up from 9 to 11 p.m., leaving children unprotected during a significant period of sandfly-biting hours after sunset. Regression analysis of incidence data from 114 villages demonstrated a significant reduction of VL by village and month following ITN provision. The greatest effect was 17-20 months post-intervention, with VL cases reduced by 59% (95% CI: 25-78%). An estimated 1060 VL cases were prevented between June 1999 and January 2001, a mean protective effect of 27%. Although results need to be interpreted with caution, this analysis indicates a potentially strong reduction in VL incidence following a community distribution of ITN. The effectiveness of ITN depends on behavioural factors, which differ between communities
Global Gene Expression and Systems Biology Analysis of Bovine Monocyte-Derived Macrophages in Response to In Vitro Challenge with Mycobacterium bovis
No full textpeer-reviewedBackground
Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array.
Results
Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis.
Conclusions
The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.Science Foundation Ireland (www.sfi.ie) Investigator grants (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038); Department of Agriculture, Fisheries and Food (www.agriculture.ie) Research Stimulus Grant (No: RSF 06 405); European Union Framework 7 (http://cordis.europa.eu/fp7) Project Grant (No: KBBE-211602-MACROSYS); Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and
Systems Biology PhD Programme (http://bioinfo-casl.ucd.ie/PhD)
Improved statistical method for quality control of hydrographic observations
No full textAuthor Posting. © American Meteorological Society, 2020. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of the Atmospheric and Oceanic Technology 37(5), (2020): 789-806, doi:10.1175/JTECH-D-18-0244.1.Realistic ocean state prediction and its validation rely on the availability of high quality in situ observations. To detect data errors, adequate quality check procedures must be designed. This paper presents procedures that take advantage of the ever-growing observation databases that provide climatological knowledge of the ocean variability in the neighborhood of an observation location. Local validity intervals are used to estimate binarily whether the observed values are considered as good or erroneous. Whereas a classical approach estimates validity bounds from first- and second-order moments of the climatological parameter distribution, that is, mean and variance, this work proposes to infer them directly from minimum and maximum observed values. Such an approach avoids any assumption of the parameter distribution such as unimodality, symmetry around the mean, peakedness, or homogeneous distribution tail height relative to distribution peak. To reach adequate statistical robustness, an extensive manual quality control of the reference dataset is critical. Once the data have been quality checked, the local minima and maxima reference fields are derived and the method is compared with the classical mean/variance-based approach. Performance is assessed in terms of statistics of good and bad detections. It is shown that the present size of the reference datasets allows the parameter estimates to reach a satisfactory robustness level to always make the method more efficient than the classical one. As expected, insufficient robustness persists in areas with an especially low number of samples and high variability.This study has been conducted using EU Copernicus Marine Service Information and was supported by the European Union within the EU Copernicus Marine Service In Situ phase-I and phase-II contracts led by Ifremer. The publication was also supported by SOERE CTDO2 in France. The Argo data were collected and made freely available by the International Argo Program and the national programs that contribute to it (see http://www.argo.ucsd.edu, http://argo.jcommops.org). The Argo Program is part of the Global Ocean Observing System (http://doi.org/10.17882/42182). The marine mammal data were collected and made freely available by the International MEOP Consortium and the national programs that contribute to it (see http://www.meop.net; https://doi.org/10.17882/45461). Aleix Gelabert and Dídac Costa were the skippers of the OPOO, sponsored by the Intergovernmental Oceanographic Commission (UNESCO) and Pharmaton. The BWR is a periodic oceanic race organized by the Fundació Navegació Oceànica de Barcelona (FNOB). Reviewer D. Briand provided some useful comments on the final version of the draft paper before submission.2020-11-0
Comparative functional genomics and the bovine macrophage response to strains of the Mycobacterium genus
No full textMycobacterial infections are major causes of morbidity and mortality in cattle and are also potential zoonotic agents with implications for human health. Despite the implementation of comprehensive animal surveillance programs, many mycobacterial diseases have remained recalcitrant to eradication in several industrialized countries. Two major mycobacterial pathogens of cattle are Mycobacterium bovis and M. avium subspecies paratuberculosis (MAP), the causative agents of bovine tuberculosis and Johne’s disease, respectively. Bovine tuberculosis is a chronic, granulomatous disease of the respiratory tract that is spread via aerosol transmission, while Johne’s disease is a chronic granulomatous disease of the intestines that is transmitted via the fecal-oral route. Although these diseases exhibit differential tissue tropism and distinct complex etiologies, both M. bovis and MAP infect, reside and replicate in host macrophages—the key host innate immune cell that encounters mycobacterial pathogens after initial exposure and mediates the subsequent immune response. The persistence of M. bovis and MAP in macrophages relies on a diverse series of immunomodulatory mechanisms, including the inhibition of phagosome maturation and apoptosis, generation of cytokine-induced necrosis enabling dissemination of infection through the host, local pathology, and ultimately shedding of the pathogen. Here, we review the bovine macrophage response to infection with M. bovis and MAP. In particular, we describe how recent advances in functional genomics are shedding light on the host macrophage-pathogen interactions that underlie different mycobacterial diseases. To illustrate this, we present new analyses of previously published bovine macrophage transcriptomics data following in vitro infection with virulent M. bovis, the attenuated vaccine strain M. bovis BCG, and MAP, and discuss our findings with respect to the differing etiologies of bovine tuberculosis and Johne’s disease
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