| 1. |
- Bachmann, Jörg A., 1989-, et al.
(författare)
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Evolutionary stability of genetic dominance in the Brassicaceae self-incompatibility system
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The question of whether dominance-recessivity relationships between associated alleles in a diploid genotype can evolve independently from the activity of the gene products encoded has been a hot topic in evolutionary genetics throughout the 20th century. In hermaphroditic plants of the Brassicaceae family, the self-incompatibility locus (S-locus) confers the ability to recognize and reject self-pollen. Dominance relationships between self-incompatibility alleles (S-alleles) in pollen are governed by small RNA (sRNA) transcriptional regulators produced by dominant S-alleles and their target sites on recessive S-alleles. These regulators and their target sites segregate together with but are distinct from the genes encoding self-recognition specificities themselves, providing the opportunity for dominance to evolve independently from the recognition specificities. Dominance interactions between the many segregating S-alleles have been described in the distantly related Arabidopsis and Brassica, but little is known about the evolutionary stability of the dominance networks given that divergent sets of S-alleles are segregating in these two genera. In this study, we take advantage of the extensive trans-specific sharing of S-haplotypes between the self-incompatible species Capsella grandiflora and Arabidopsis halleri to investigate the conservation of S-locus dominance relationships across their approximately 8 million years of divergence. For this purpose, we use a combination of controlled crosses and full-length long-read sequencing of S-haplotypes. We find that the dominance network among six C. grandiflora S-alleles has a largely parallel structure to that among their orthologous S-alleles in A. halleri. We test the theoretical prediction that dominant S-alleles should be found at lower population frequencies using a large sample of a natural C. grandiflora population. Finally, we test whether dominant C. grandiflora S-alleles show increased accumulation of repeats (TEs) than recessive S-alleles, as expected due to their lower chance of recombination and lower effective population sizes. Our results contribute to an improved understanding of the maintenance of dominance relationships at loci under balancing selection.
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| 2. |
- Bachmann, Julie, et al.
(författare)
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Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria
- 2014
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 10:4, s. e1004038-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.
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| 3. |
- Bachmann, Julie, et al.
(författare)
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Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range
- 2011
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Ingår i: Molecular Systems Biology. - : Nature Publishing Group / European Molecular Biology Organization. - 1744-4292 .- 1744-4292. ; 7:516
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Tidskriftsartikel (refereegranskat)abstract
- Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. The specific contributions of individual feedback regulators, however, remain unclear. Based on extensive time-resolved data sets in primary erythroid progenitor cells, we established a dynamic pathway model to dissect the roles of the two transcriptional negative feedback regulators of the suppressor of cytokine signaling (SOCS) family, CIS and SOCS3, in JAK2/STAT5 signaling. Facilitated by the model, we calculated the STAT5 response for experimentally unobservable Epo concentrations and provide a quantitative link between cell survival and the integrated response of STAT5 in the nucleus. Model predictions show that the two feedbacks CIS and SOCS3 are most effective at different ligand concentration ranges due to their distinct inhibitory mechanisms. This divided function of dual feedback regulation enables control of STAT5 responses for Epo concentrations that can vary 1000-fold in vivo. Our modeling approach reveals dose-dependent feedback control as key property to regulate STAT5-mediated survival decisions over a broad range of ligand concentrations.
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