| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Ching, Yung-Hao, et al.
(författare)
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High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5
- 2010
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Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 11, s. 106-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a similar to 50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals. Results: We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis. Conclusion: This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.
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| 5. |
- Ahmad, F, et al.
(författare)
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Cyclic nucleotide phosphodiesterase 3B is a downstream target of protein kinase B and may be involved in regulation of effects of protein kinase B on thymidine incorporation in FDCP2 cells
- 2000
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Ingår i: Journal of Immunology. - 1550-6606. ; 164:9, s. 4678-4688
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Tidskriftsartikel (refereegranskat)abstract
- Wild-type (F/B), constitutively active (F/B*), and three kinase-inactive (F/Ba-, F/Bb-, F/Bc-) forms of Akt/protein kinase B (PKB) were permanently overexpressed in FDCP2 cells. In the absence of insulin-like growth factor-1 (IGF-1), activities of PKB, cyclic nucleotide phosphodiesterase 3B (PDE3B), and PDE4 were similar in nontransfected FDCP2 cells, mock-transfected (F/V) cells, and F/B and F/B- cells. In F/V cells, IGF-1 increased PKB, PDE3B, and PDE4 activities approximately 2-fold. In F/B cells, IGF-1, in a wortmannin-sensitive manner, increased PKB activity approximately 10-fold and PDE3B phosphorylation and activity ( approximately 4-fold), but increased PDE4 to the same extent as in F/V cells. In F/B* cells, in the absence of IGF-1, PKB activity was markedly increased ( approximately 10-fold) and PDE3B was phosphorylated and activated (3- to 4-fold); wortmannin inhibited these effects. In F/B* cells, IGF-1 had little further effect on PKB and activation/phosphorylation of PDE3B. In F/B- cells, IGF-1 activated PDE4, not PDE3B, suggesting that kinase-inactive PKB behaved as a dominant negative with respect to PDE3B activation. Thymidine incorporation was greater in F/B* cells than in F/V cells and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor. In F/B cells, IGF-1-induced phosphorylation of the apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide. Activated PKB phosphorylated and activated rPDE3B in vitro. These results suggest that PDE3B, not PDE4, is a target of PKB and that activated PDE3B may regulate cAMP pools that modulate effects of PKB on thymidine incorporation and BAD phosphorylation in FDCP2 cells.
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| 7. |
- Liu, X. D., et al.
(författare)
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Origin and expansion of the world's most widespread pinniped: Range-wide population genomics of the harbour seal (Phoca vitulina)
- 2022
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 31:6, s. 1682-1699
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Tidskriftsartikel (refereegranskat)abstract
- The harbour seal (Phoca vitulina) is the most widely distributed pinniped, occupying a wide variety of habitats and climatic zones across the Northern Hemisphere. Intriguingly, the harbour seal is also one of the most philopatric seals, raising questions as to how it colonized its current range. To shed light on the origin, remarkable range expansion, population structure and genetic diversity of this species, we used genotyping-by-sequencing to analyse similar to 13,500 biallelic single nucleotide polymorphisms from 286 individuals sampled from 22 localities across the species' range. Our results point to a Northeast Pacific origin of the harbour seal, colonization of the North Atlantic via the Canadian Arctic, and subsequent stepping-stone range expansions across the North Atlantic from North America to Europe, accompanied by a successive loss of genetic diversity. Our analyses further revealed a deep divergence between modern North Pacific and North Atlantic harbour seals, with finer-scale genetic structure at regional and local scales consistent with strong philopatry. The study provides new insights into the harbour seal's remarkable ability to colonize and adapt to a wide range of habitats. Furthermore, it has implications for current harbour seal subspecies delineations and highlights the need for international and national red lists and management plans to ensure the protection of genetically and demographically isolated populations.
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| 9. |
- Grankvist, Anna, et al.
(författare)
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Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
- 2014
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 58:12, s. 1716-1722
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Tidskriftsartikel (refereegranskat)abstract
- Background. Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. Methods.aEuro integral We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. Results.aEuro integral The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Conclusions.aEuro integral Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
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| 10. |
- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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| 13. |
- Reeve, Janice L. V., et al.
(författare)
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OxLDL-induced gene expression patterns in CASMC are mimicked in apoE(-/-) mice aortas
- 2007
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 356:3, s. 681-686
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Tidskriftsartikel (refereegranskat)abstract
- Oxidized low density lipoprotein (oxLDL) contributes to the pathophysiology of atherosclerosis, partly by altering gene expression in vascular cells. Here, we show 221 genes differentially regulated by oxLDL in coronary artery smooth muscle cells (CASMC), using oligonucleotide microarrays. These genes were classified into 14 functional groups. A comparable gene expression pattern was detected in apoE(-/-) mice. OxLDL induced an oxidative stress response in CASMC, but not the unfolded protein response. OxLDL also caused CASMC death which was accompanied by increased expression of FasL, Bax, and p53 but was caspase-independent. This approach provides further insight into disease pathology and prognosis. (c) 2007 Elsevier Inc. All rights reserved.
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| 20. |
- Yu, L., et al.
(författare)
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Multi-layer mucilage of Plantago ovata seeds : Rheological differences arise from variations in arabinoxylan side chains
- 2017
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Ingår i: Carbohydrate Polymers. - : Elsevier Ltd. - 0144-8617 .- 1879-1344. ; 165, s. 132-141
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Tidskriftsartikel (refereegranskat)abstract
- Mucilages are hydrocolloid solutions produced by plants for a variety of functions, including the creation of a water-holding barrier around seeds. Here we report our discovery of the formation of three distinct mucilage layers around Plantago ovata seeds upon their hydration. Each layer is dominated by different arabinoxylans (AXs). These AXs are unusual because they are highly branched and contain β-1,3-linked xylose in their side chains. We show that these AXs have similar monosaccharide and linkage composition, but vary in their polymer conformation. They also exhibit distinct rheological properties in aqueous solution, despite analytical techniques including NMR showing little difference between them. Using enzymatic hydrolysis and chaotropic solvents, we reveal that hydrogen bonding and side chain distribution are key factors underpinning the distinct rheological properties of these complex AXs.
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