| 1. |
- Eneslätt, Kjell, et al.
(författare)
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Signatures of T cells as correlates of immunity to Francisella tularensis
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e32367-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia or vaccination with the live vaccine strain (LVS) of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (naive). Significant differences were detected between either of the immune donor groups and naive individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-gamma, MCP-1, and MIP-1 beta. Expression of IFN-gamma, MIP-1 beta, and CD107a by CD4(+)CD45RO(+) or CD8(+) CD45RO(+) T cells correlated to antigen concentrations. In particular, IFN-gamma and MIP-1 beta strongly discriminated between immune and naive individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-alpha-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.
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| 2. |
- Espaillat, Akbar, master, 1988-, et al.
(författare)
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Chemometric Analysis of Bacterial Peptidoglycan Reveals Atypical Modifications That Empower the Cell Wall against Predatory Enzymes and Fly Innate Immunity
- 2016
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 138:29, s. 9193-9204
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Tidskriftsartikel (refereegranskat)abstract
- Peptidoglycan is a fundamental structure for most bacteria. It contributes to the cell morphology and provides cell wall integrity against environmental insults. While several studies have reported a significant degree of variability in the chemical composition and organization of peptidoglycan in the domain Bacteria, the real diversity of this polymer is far from fully explored. This work exploits rapid ultraperformance liquid chromatography and multivariate data analysis to uncover peptidoglycan chemical diversity in the Class Alphaproteobacteria, a group of Gram negative bacteria that are highly heterogeneous in terms of metabolism, morphology and life-styles. Indeed, chemometric analyses revealed novel peptidoglycan structures conserved in Acetobacteria: amidation at the alpha-(L)-carboxyl of meso-diaminopimelic acid and the presence of muropeptides cross-linked by (1-3) L-Ala-D-(meso)diaminopimelate cross-links. Both structures are growth-controlled modifications that influence sensitivity to Type VI secretion system peptidoglycan endopeptidases and recognition by the Drosophila innate immune system, suggesting relevant roles in the environmental adaptability of these bacteria. Collectively our findings demonstrate the discriminative power of chemometric tools on large cell wall-chromatographic data sets to discover novel peptidoglycan structural properties in bacteria.
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| 3. |
- Law, Simon R, et al.
(författare)
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Centralization Within Sub-Experiments Enhances the Biological Relevance of Gene Co-expression Networks : A Plant Mitochondrial Case Study
- 2020
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Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Gene co-expression networks (GCNs) can be prepared using a variety of mathematical approaches based on data sampled across diverse developmental processes, tissue types, pathologies, mutant backgrounds, and stress conditions. These networks are used to identify genes with similar expression dynamics but are prone to introducing false-positive and false-negative relationships, especially in the instance of large and heterogenous datasets. With the aim of optimizing the relevance of edges in GCNs and enhancing global biological insight, we propose a novel approach that involves a data-centering step performed simultaneously per gene and per sub-experiment, called centralization within sub-experiments (CSE). Using a gene set encoding the plant mitochondrial proteome as a case study, our results show that all CSE-based GCNs assessed had significantly more edges within the majority of the considered functional sub-networks, such as the mitochondrial electron transport chain and its complexes, than GCNs not using CSE; thus demonstrating that CSE-based GCNs are efficient at predicting canonical functions and associated pathways, here referred to as the core gene network. Furthermore, we show that correlation analyses using CSE-processed data can be used to fine-tune prediction of the function of uncharacterized genes; while its use in combination with analyses based on non-CSE data can augment conventional stress analyses with the innate connections underpinning the dynamic system being examined. Therefore, CSE is an effective alternative method to conventional batch correction approaches, particularly when dealing with large and heterogenous datasets. The method is easy to implement into a pre-existing GCN analysis pipeline and can provide enhanced biological relevance to conventional GCNs by allowing users to delineate a core gene network. Author Summary Gene co-expression networks (GCNs) are the product of a variety of mathematical approaches that identify causal relationships in gene expression dynamics but are prone to the misdiagnoses of false-positives and false-negatives, especially in the instance of large and heterogenous datasets. In light of the burgeoning output of next-generation sequencing projects performed on a variety of species, and developmental or clinical conditions; the statistical power and complexity of these networks will undoubtedly increase, while their biological relevance will be fiercely challenged. Here, we propose a novel approach to generate a "core" GCN with enhanced biological relevance. Our method involves a data-centering step that effectively removes all primary treatment/tissue effects, which is simple to employ and can be easily implemented into pre-existing GCN analysis pipelines. The gain in biological relevance resulting from the adoption of this approach was assessed using a plant mitochondrial case study.
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| 4. |
- Lembrechts, Jonas J., et al.
(författare)
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Global maps of soil temperature
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
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Tidskriftsartikel (refereegranskat)abstract
- Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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| 5. |
- Lembrechts, Jonas J., et al.
(författare)
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SoilTemp : A global database of near-surface temperature
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
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Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
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| 6. |
- Normark, Johan, et al.
(författare)
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Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model
- 2014
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Ingår i: PLOS ONE. - : PLOS ONE. - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1 beta and TNF-alpha, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.
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| 7. |
- Rydén, Patrik, 1969-, et al.
(författare)
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Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence
- 2012
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 205:2, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data.Methods. A prediction model for mosquito abundance was built using weather and mosquito catch data. Then a negative binomial regression model based on the predicted mosquito abundance and local weather data was built to predict annual numbers of humans contracting tularemia in Dalarna County, Sweden.Results. Three hundred seventy humans were diagnosed with tularemia between 1981 and 2007, 94% of them during 7 summer outbreaks. Disease transmission was concentrated along rivers in the area. The predicted mosquito abundance was correlated (0.41, P < .05) with the annual number of human cases. The predicted mosquito peaks consistently preceded the median onset time of human tularemia (temporal correlation, 0.76; P < .05). Our final predictive model included 5 environmental variables and identified 6 of the 7 outbreaks.Conclusions. This work suggests that a high prevalence of mosquitoes in late summer is a prerequisite for outbreaks of tularemia in a tularemia-endemic boreal forest area of Sweden and that environmental variables can be used as risk indicators.
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