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  • Andersson, Åsa, et al. (författare)
  • Impaired autoimmune T helper 17 cell responses following DNA vaccination against rat experimental autoimmune encephalomyelitis
  • 2008
  • Ingår i: PLoS ONE. - PLoS. - 1932-6203. - 1932-6203 (Electronic) ; 3:11, s. e3682
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91-108) (pMOG) suppresses MOG(91-108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-beta. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-beta1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-beta in the protective mechanism we employed short interfering RNA (siRNA) to IFN-beta in the DNA vaccine. SiRNA to IFN-beta completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-beta is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-beta-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-beta as IL-17 responses are rescued by silencing of IFN-beta during DNA vaccination.
  • Delhomme, N., et al. (författare)
  • Serendipitous Meta-Transcriptomics The Fungal Community of Norway Spruce (Picea abies)
  • 2015
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. - 1932-6203 (Electronic) 1932-6203 (Linking) ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.
  • Hayward, Alexander, et al. (författare)
  • ZBED Evolution Repeated Utilization of DNA Transposons as Regulators of Diverse Host Functions
  • 2013
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. - 1932-6203 (Electronic) 1932-6203 (Linking) ; 8:3, s. e59940
  • Tidskriftsartikel (refereegranskat)abstract
    • ZBED genes originate from domesticated hAT DNA transposons and encode regulatory proteins of diverse function in vertebrates. Here we reveal the evolutionary relationship between ZBED genes and demonstrate that they are derived from at least two independent domestication events in jawed vertebrate ancestors. We show that ZBEDs form two monophyletic clades, one of which has expanded through several independent duplications in host lineages. Subsequent diversification of ZBED genes has facilitated regulation of multiple diverse fundamental functions. In contrast to known examples of transposable element exaptation, our results demonstrate a novel unprecedented capacity for the repeated utilization of a family of transposable element-derived protein domains sequestered as regulators during the evolution of diverse host gene functions in vertebrates. Specifically, ZBEDs have contributed to vertebrate regulatory innovation through the donation of modular DNA and protein interacting domains. We identify that C7ORF29, ZBED2, 3, 4, and ZBEDX form a monophyletic group together with ZBED6, that is distinct from ZBED1 genes. Furthermore, we show that ZBED5 is related to Buster DNA transposons and is phylogenetically separate from other ZBEDs. Our results offer new insights into the evolution of regulatory pathways, and suggest that DNA transposons have contributed to regulatory complexity during genome evolution in vertebrates.
  • Pocock, Tessa, et al. (författare)
  • Negative Impact on Growth and Photosynthesis in the Green Alga Chlamydomonas reinhardtii in the Presence of the Estrogen 17alpha-Ethynylestradiol
  • 2014
  • Ingår i: PLoS ONE. - 1932-6203. - 1932-6203 (Electronic) 1932-6203 (Linking) ; 9:10, s. e109289
  • Tidskriftsartikel (refereegranskat)abstract
    • It is well known that estrogenic compounds affect development of fertilized eggs of many species of birds, fish and amphibians through disrupted activity of carbonic anhydrase (CA). The most potent activity comes from the most commonly occurring synthetic sterol, 17alpha-Ethynylestradiol (EE2). Less is known about the responses of aquatic phytoplankton to these compounds. Here we show for the first time that, in comparision to the control, the addition of 7 microM EE2 reduced the growth rate of the green alga Chlamydomonas reinhardtii by 68% for cells grown at high CO2. When cells were grown in ambient air (low Ci) with a fully activated carbon concentrating mechanism through the induction of CA activity, the growth rates were reduced by as much as 119%. A reduced growth rate could be observed at EE2 concentrations as low as 10 pM. This was accompanied by a reduced maximum capacity for electron transport in photosystem II as determined by a lower FV/FM for low Ci-grown cells, which indicates the involvement of CAH3, a CA specifically located in the thylakoid lumen involved in proton pumping across the thylakoid membranes. These results were in agreement with an observed reduction in the chloroplastic affinity for Ci as shown by a strong increase in the Michaelis-Menten K0.5 for HCO3-. In itself, a lowering of the growth rate of a green alga by addition of the sterol EE2 warrants further investigation into the potential environmental impact by the release of treated waste water.
  • Sanchez-Martinez, Silvia, et al. (författare)
  • Studies on the Restriction of Murine Leukemia Viruses by Mouse APOBEC3
  • 2012
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. - 1932-6203 (Electronic) 1932-6203 (Linking) ; 7:5, s. e38190
  • Tidskriftsartikel (refereegranskat)abstract
    • APOBEC3 proteins function to restrict the replication of retroviruses. One mechanism of this restriction is deamination of cytidines to uridines in (-) strand DNA, resulting in hypermutation of guanosines to adenosines in viral (+) strands. However, Moloney murine leukemia virus (MoMLV) is partially resistant to restriction by mouse APOBEC3 (mA3) and virtually completely resistant to mA3-induced hypermutation. In contrast, the sequences of MLV genomes that are in mouse DNA suggest that they were susceptible to mA3-induced deamination when they infected the mouse germline. We tested the possibility that sensitivity to mA3 restriction and to deamination resides in the viral gag gene. We generated a chimeric MLV in which the gag gene was from an endogenous MLV in the mouse germline, while the remainder of the viral genome was from MoMLV. This chimera was fully infectious but its response to mA3 was indistinguishable from that of MoMLV. Thus, the Gag protein does not seem to control the sensitivity of MLVs to mA3. We also found that MLVs inactivated by mA3 do not synthesize viral DNA upon infection; thus mA3 restriction of MLV occurs before or at reverse transcription. In contrast, HIV-1 restricted by mA3 and MLVs restricted by human APOBEC3G do synthesize DNA; these DNAs exhibit APOBEC3-induced hypermutation.
  • Aalaei, Kataneh, et al. (författare)
  • Early and advanced stages of Maillard reaction in infant formulas : Analysis of available lysine and carboxymethyl-lysine
  • 2019
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the literature on the Maillard reaction in infant formulas is extensive, most studies have focused on model systems, and in only a few cases on real food systems. Therefore, the objective of the present study was to determine the status of the Maillard reaction, both the early and advanced phases, in a variety of commercial infant formulas available on the Swedish market. Ten powder and liquid milk-based infant formulas from three manufacturers were selected to determine available lysine and CML contents, the two established indicators of the reaction. The products were also characterized with respect to protein content, carbohydrates composition, water content and water activity. In order to be able to compare the impact of different processing steps applied on powder and liquid formulas, the solid formulas contained similar ingredients as their corresponding liquid ones. Our findings showed that powder and liquid formulas contained similar available lysine concentrations regardless of the manufacturer, showing 27.14–36.57% decrease in the available lysine, compared to the reference skim milk powder in this study. The CML concentrations were in a broad range of 68.77–507.99 mg/kg protein. In the case of one manufacturer, liquid infant formulas had significantly higher CML content, compared to the powder products (p < 0.05). The results from this study are a step taken towards better understanding of the extent of the Maillard reaction in real complex systems of infant formulas.
  • Abariute, Laura, et al. (författare)
  • Uptake of nanowires by human lung adenocarcinoma cells
  • 2019
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Semiconductor nanowires are increasingly used in optoelectronic devices. However, their effects on human health have not been assessed fully. Here, we investigate the effects of gallium phosphide nanowires on human lung adenocarcinoma cells. Four different geometries of nanowires were suspended in the cell culture for 48 hours. We show that cells internalize the nanowires and that the nanowires have no effect on cell proliferation rate, motility, viability and intracellular ROS levels. By blocking specific internalization pathways, we demonstrate that the nanowire uptake is the result of a combination of processes, requiring dynamin and actin polymerization, which suggests an internalization through macropinocytosis and phagocytosis.
  • Abate, Ebba, et al. (författare)
  • The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia
  • 2012
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 7:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.
  • Abbas, Abdul-Karim, 1959- (författare)
  • Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats
  • 2016
  • Ingår i: Plos One. - 1932-6203. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary.
  • Abbott, Jessica K., et al. (författare)
  • Epigenetics and Sex-Specific Fitness: An Experimental Test Using Male-Limited Evolution in Drosophila melanogaster.
  • 2013
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 8:7
  • Tidskriftsartikel (refereegranskat)abstract
    • When males and females have different fitness optima for the same trait but share loci, intralocus sexual conflict is likely to occur. Epigenetic mechanisms such as genomic imprinting (in which expression is altered according to parent-of-origin) and sex-specific maternal effects have been suggested as ways by which this conflict can be resolved. However these ideas have not yet been empirically tested. We designed an experimental evolution protocol in Drosophila melanogaster that enabled us to look for epigenetic effects on the X-chromosome-a hotspot for sexually antagonistic loci. We used special compound-X females to enforce father-to-son transmission of the X-chromosome for many generations, and compared fitness and gene expression levels between Control males, males with a Control X-chromosome that had undergone one generation of father-son transmission, and males with an X-chromosome that had undergone many generations of father-son transmission. Fitness differences were dramatic, with experimentally-evolved males approximately 20% greater than controls, and with males inheriting a non-evolved X from their father about 20% lower than controls. These data are consistent with both strong intralocus sexual conflict and misimprinting of the X-chromosome under paternal inheritance. However, expression differences suggested that reduced fitness under paternal X inheritance was largely due to deleterious maternal effects. Our data confirm the sexually-antagonistic nature of Drosophila's X-chromosome and suggest that the response to male-limited X-chromosome evolution entails compensatory evolution for maternal effects, and perhaps modification of other epigenetic effects via coevolution of the sex chromosomes.
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