| 1. |
- Åberg, Anna, et al.
(författare)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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| 2. |
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| 3. |
- Björkblom, Benny, et al.
(författare)
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Distinct metabolic hallmarks of WHO classified adult glioma subtypes
- 2022
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:9, s. 1454-1468
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.METHODS: Cross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors - oligodendroglioma (n=31), astrocytoma (n=31) and glioblastoma (n=162) - were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2-4, and MGMT promoter methylation.RESULTS: Distinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.CONCLUSION: Key metabolic differences exist across adult glioma subtypes.
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| 4. |
- Brännström, Pär A
(författare)
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Visual ecology of insect superposition eyes
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the superposition compound eye each rhabdom (light sensitive unit) receives light through many ommatidial facets, while in the apposition compound eye every rhabdom receives light from a single facet. The superposition design increases photon capture, which is an advantage in dark environments. Despite their advantage in dim light, superposition eyes can sometimes be found in insects that live in brighter habitats. The aim of this thesis is to study visual adaptations in insects with superposition eyes. Animals with different lifestyles and activity patterns have been selected for this study. A more general theoretical analysis of the design of superposition eyes is also included in this thesis. The dorsal eyes of male mayflies (family Baetidae) are used only to detect females flying against the sky. Male mayflies that swarm in open habitats where a large portion of the sky is visible, have eyes with large fields of view but with a poor resolution. Other species swarm in forests, and have highly resolved tubular eyes with narrow fields of view that match the visible patches of sky. The elephant hawkmoth (Deilephila elpenor) has superposition eyes adapted for hovering in front of flowers while collecting nectar at night. The eye possesses smooth regional differences. The largest apertures, highest sensitivities and the largest binocular overlap are found in the anterio-ventral region of the eye with which they fixate flowers while feeding. They also have the poorest anatomical resolution in this region. The tiger beetle Cicindela hybrida has an eye that is optimised for visual hunting in a flat environment. It has an apposition eye during the day with a pronounced visual streak (horizontal acute zone) that forms a binocular acute zone at the front of the eye. The eye design matches their hunting behaviour and includes tilting of the head to fixate prey. The tropical tiger beetle Odontocheila chrysis, a close relative of Cicindela hybrida, lives in dark forest habitats and has superposition eyes both during the day and at night and no pronounced regional differences. The bright habitat of Cicindela has resulted in the evolution of apposition eyes, which permit pronounced regional differences, while in Odontocheila superposition eyes provide optimal vision in a dark environment but with limited possibilities for regional differences. Data from real eyes were compared to computer models to asses the basic principles and constraints in superposition eye design. We found several basic assumptions about superposition eye design to be incorrect: (1) the incident and exit angles in each optical unit are not equal for all angles, (2) the focal plane is not always located at half the radius of the whole eye, and (3) spherical aberration is not a major limitation to resolution in superposition eyes. The main conclusion of this analysis is that selection for design tolerance is an overlooked evolutionary force.
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| 5. |
- Henriksson, Roger, et al.
(författare)
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High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.
- 2006
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Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 78:3, s. 321-6
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.
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| 6. |
- Rask, Katarina, 1966, et al.
(författare)
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Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3 beta
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1298-1304
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Tidskriftsartikel (refereegranskat)abstract
- Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.
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