| 1. |
- Morrison, Hilary G., et al.
(författare)
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Genomic minimalism in the early diverging intestinal parasite Giardia lamblia
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 317:5846, s. 1921-1926
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Tidskriftsartikel (refereegranskat)abstract
- The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.
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| 2. |
- Birkeland, Shanda R., et al.
(författare)
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Transcriptome analyses of the Giardia lamblia life cycle
- 2010
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 174:1, s. 62-65
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Tidskriftsartikel (refereegranskat)abstract
- We quantified mRNA abundance from 10 stages in the Giardia lamblia life cycle in vitro using Serial Analysis of Gene Expression (SAGE). 163 abundant transcripts were expressed constitutively. 71 transcripts were upregulated specifically during excystation and 42 during encystation. Nonetheless, the transcriptomes of cysts and trophozoites showed major differences. SAGE detected co-expressed clusters of 284 transcripts differentially expressed in cysts and excyzoites and 287 transcripts in vegetative trophozoites and encysting cells. All clusters included known genes and pathways as well as proteins unique to Giardia or diplomonads. SAGE analysis of the Giardia life cycle identified a number of kinases, phosphatases, and DNA replication proteins involved in excystation and encystation, which could be important for examining the roles of cell signaling in giardial differentiation. Overall, these data pave the way for directed gene discovery and a better understanding of the biology of G. lamblia.
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| 3. |
- Ferella, Marcela, et al.
(författare)
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Gene expression changes during Giardia-host cell interactions in serum-free medium
- 2014
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 197:1-2, s. 21-23
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Tidskriftsartikel (refereegranskat)abstract
- Serial Analysis of Gene Expression (SAGE) was used to quantify transcriptional changes in Giardia intestinalis during its interaction with human intestinal epithelial cells (IECs, HT-29) in serum free M199 medium. Transcriptional changes were compared to those in trophozoites alone in M199 and in TYI-S-33 Giardia growth medium. In total, 90 genes were differentially expressed, mainly those involved in cellular redox homeostasis, metabolism and small molecule transport but also cysteine proteases and structural proteins of the giardin family. Only 29 genes changed their expression due to IEC interaction and the rest were due to M199 medium. Although our findings generated a small dataset, it was consistent with our earlier microarray studies performed under different interaction conditions. This study has confined the number of genes in Giardia to a small subset that specifically change their expression due to interaction with IECs.
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| 4. |
- Ferrero, L., et al.
(författare)
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Determining the Aethalometer multiple scattering enhancement factor C from the filter loading parameter
- 2024
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Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 917
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Tidskriftsartikel (refereegranskat)abstract
- Light-absorbing aerosols heat the atmosphere; an accurate quantification of their absorption coefficient is mandatory. However, standard reference instruments (CAPS, MAAP, PAX, PTAAM) are not always available at each measuring site around the world.By integrating all previous published studies concerning the Aethalometers, the AE33 filter loading parameter, provided by the dual-spot algorithm, were used to determine the multiple scattering enhancement factor from the Aethalometer itself (hereinafter CAE) on an yearly and a monthly basis. The method was developed in Milan, where Aethalometer measurements were compared with MAAP data; the comparison showed a good agreement in terms of equivalent black carbon (R2 = 0.93; slope = 1.02 and a negligible intercept = 0.12 μg m−3) leading to a yearly experimental multiple scattering enhancement factor of 2.51 ± 0.04 (hereinafter CMAAP). On a yearly time base the CAE values obtained using the new approach was 2.52 ± 0.01, corresponding to the experimental one (CMAAP). Considering the seasonal behavior, higher experimental CMAAP and computed CAE values were found in summer (2.83 ± 0.12) whereas, the lower ones in winter/early-spring (2.37 ± 0.03), in agreement with the single scattering albedo behavior in the Po Valley.Overall, the agreement between the experimental CMAAP and CAE showed a root mean squared error (RMSE) of just 0.038 on the CMAAP prediction, characterized by a slope close to 1 (1.001 ± 0.178), a negligible intercept (−0.002 ± 0.455) and a high degree of correlation (R2 = 0.955). From an environmental point of view, the application of a dynamic (space/time) determination of CAE increases the accuracy of the aerosol heating rate (compared to applying a fixed C value) up to 16 % solely in Milan, and to 114 % when applied in the Arctic at 80°N.
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| 5. |
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| 6. |
- Lauwaet, Tineke, et al.
(författare)
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Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation
- 2007
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 152:1, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- The ability of Giardia lamblia to undergo two distinct differentiations in response to physiologic stimuli is central to its pathogenesis. The giardial cytoskeleton changes drastically during encystation and excystation. However, the signal transduction pathways mediating these transformations are poorly understood. We tested the hypothesis that PP2A, a highly conserved serine/threonine protein phosphatase, might be important in giardial differentiation. We found that in vegetatively growing trophozoites, gPP2A-C protein localizes to basal bodies/centrosomes, and to cytoskeletal structures unique to Giardia: the ventral disk, and the dense rods of the anterior, posterior-lateral, and caudal flagella. During encystation, gPP2A-C protein disappears from only the anterior flagellar dense rods. During excystation, gPP2A-C localizes to the cyst wall in excysting cysts but is not found in the wall of cysts with emerging excyzoites. Transcriptome and immunoblot analyses indicated that gPP2A-C mRNA and protein are upregulated in mature cysts and during the early stage of excystation that models passage through the host stomach. Stable expression of gPP2A-C antisense RNA did not affect vegetative growth, but strongly inhibited the formation of encystation secretory vesicles (ESV) and water-resistant cysts. Moreover, the few cysts that formed were highly defective in excystation. Thus, gPP2A-C localizes to universal cytoskeletal structures and to structures unique to Giardia. It is also important for encystation and excystation, crucial giardial transformations that entail entry into and exit from dormancy.
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| 7. |
- Wheal, Amanda J., et al.
(författare)
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Cannabidiol Improves Vasorelaxation in Zucker Diabetic Fatty Rats through Cyclooxygenase Activation
- 2014
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 351:2, s. 457-466
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Tidskriftsartikel (refereegranskat)abstract
- Cannabidiol (CBD) decreases insulitis, inflammation, neuropathic pain, and myocardial dysfunction in preclinical models of diabetes. We recently showed that CBD also improves vasorelaxation in the Zucker diabetic fatty (ZDF) rat, and the objective of the present study was to establish the mechanisms underlying this effect. Femoral arteries from ZDF rats and ZDF lean controls were isolated, mounted on a myograph, and incubated with CBD (10 mu M) or vehicle for 2 hours. Subsequent vasorelaxant responses were measured in combination with various interventions. Prostaglandin metabolites were detected using enzyme immunoassay. Direct effects of CBD on cyclooxygenase (COX) enzyme activity were measured by oxygraph assay. CBD enhanced the maximum vasorelaxation to acetylcholine (ACh) in femoral arteries from ZDF lean rats (P < 0.01) and especially ZDF rats (P < 0.0001). In ZDF arteries, this enhancement persisted after cannabinoid receptor (CB) type 1, endothelial CB, or peroxisome proliferator-activated receptor-gamma antagonism but was inhibited by CB2 receptor antagonism. CBD also uncovered a vasorelaxant response to a CB2 agonist not previously observed. The CBD-enhanced ACh response was endothelium-, nitric oxide-, and hydrogen peroxide-independent. It was, however, COX-1/2- and superoxide dismutase-dependent, and CBD enhanced the activity of both purified COX-1 and COX-2. The CBD-enhanced ACh response in the arteries was inhibited by a prostanoid EP4 receptor antagonist. Prostaglandin E-2 metabolite levels were below the limits of detection, but 6-keto prostaglandin F-1 alpha was decreased after CBD incubation. These data show that CBD exposure enhances the ability of arteries to relax via enhanced production of vasodilator COX-1/2-derived products acting at EP4 receptors.
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