| 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. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 3. |
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| 4. |
- Illini, Oliver, et al.
(författare)
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Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
- 2024
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade >= 3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naive patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
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| 5. |
- Vikström, Anna C., et al.
(författare)
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Hemoglobin adducts as a measure of variations in exposure to acrylamide in food and comparison to questionnaire data
- 2012
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 50:7, s. 2531-2539
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Tidskriftsartikel (refereegranskat)abstract
- Measurement of haemoglobin (Hb) adducts from acrylamide (AA) and its metabolite glycidamide (GA) is a possibility to improve the exposure assessment in epidemiological studies of AA intake from food. This study aims to clarify the reliability of Hb-adduct measurement from individual single samples for exposure assessment of dietary AA intake. The intra-individual variations of AA- and GA-adduct levels measured in blood samples collected over 20 months from 13 non-smokers were up to 2-fold and 4-fold, respectively. The corresponding interindividual variations observed between 68 non-smokers, with large differences in AA intake, were 6-fold and 8-fold, respectively. The intra-individual variation of the GA-to-AA-adduct level ratio was up to 3-fold, compared to 11-fold between individuals (n = 68). From AA-adduct levels the average AA daily intake (n = 68) was calculated and compared to that estimated from dietary history methodology: 0.52 and 0.67 mu g/kg body weight and day, respectively. At an individual level the measures showed low association (Rs = 0.39). Conclusions: Dietary AA is the dominating source to measured AA-adduct levels and corresponding inter- and intra-individual variations in non-smokers. Measurements from single individual samples are useful for calculation of average M intake and its variation in a cohort, and for identification of individuals only from extreme intake groups.
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| 6. |
- Vikström, Anna, et al.
(författare)
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Teachers´solutions : a learning study about solution chemistry in grade 8
- 2013
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Ingår i: International Journal for Lesson and Learning Studies. - : Emerald. - 2046-8253 .- 2046-8261. ; 2:1, s. 26-40
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim with the paper is to describe the collective exploration, process and knowledge production made in a learning study about solution chemistry Design/methodology/approachSecondary school teachers conducted a learning study with variation theory as a guiding principle, supervised by a researcher. The relationship between teaching and learning was analyzed and evaluated in a learning study cycle of three lessons.FindingsCritical aspects when teaching solution chemistry were identified, as well as enacted patterns of variation that significantly improved students´ learning. Examples of critical aspects were the particulate character of matter, especially the feature of “empty space” between particles, the connection between macroscopic phenomenon and sub-microscopic explanations and the difference between answers with everyday language and scientific language.Practical implicationsThis suggest that teachers in a learning study can produce new knowledge as well as use earlier research results when creating teaching activities that can improve their own practical work and students´ learning. Originality/valueThe study represents an example of research with the aim to improve teachers´ practice by generating knowledge in connection with teachers´ professional tasks.
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| 7. |
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| 8. |
- Alerby, Eva, et al.
(författare)
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Ömsesidig samverkan mellan pedagogisk forskning och pedagogisk praktik
- 2010
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Ingår i: Utbildning på vetenskaplig grund. - Stockholm : Lärarförbundet. - 9789197808835 ; , s. 22-32
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Vad innebär det i praktiken att skolans och förskolans verksamhet skall vila på vetenskaplig grund och beprövad erfarenhet? Det vi tycker är intressant att lyfta fram är på vilket sätt forskningen bedrivs, hur forskningsfrågorna kommer till och hur resultaten kommer den pedagogiska praktiken tillgodo. I denna artikel diskuterar och problematiserar vi relationen mellan den pedagogiska forskningen och förskolans och skolans verksamhet. Diskussionerna exemplifieras från ett konkret forsknings- och samverkansprojekt, där forskning och praktik har gått hand i hand. Vidare ger en forskare, en doktorand, en lärarutbildare, en skolledare och en lärare sin personliga syn på samverkan mellan pedagogisk forskning och praktik.
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| 9. |
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| 10. |
- Gamero, Anna, et al.
(författare)
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Tracking Progress Toward EU Biodiversity Strategy Targets : EU Policy Effects in Preserving its Common Farmland Birds
- 2017
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Ingår i: Conservation Letters. - : Wiley. - 1755-263X. ; 10:4, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- Maximizing the area under biodiversity-related conservation measures is a main target of the European Union (EU) Biodiversity Strategy to 2020. We analyzed whether agrienvironmental schemes (AES) within EU common agricultural policy, special protected areas for birds (SPAs), and Annex I designation within EU Birds Directive had an effect on bird population changes using monitoring data from 39 farmland bird species from 1981 to 2012 at EU scale. Populations of resident and short-distance migrants were larger with increasing SPAs and AES coverage, while Annex I species had higher population growth rates with increasing SPAs, indicating that SPAs may contribute to the protection of mainly target species and species spending most of their life cycle in the EU. Because farmland birds are in decline and the negative relationship of agricultural intensification with their population growth rates was evident during the implementation of AES and SPAs, EU policies seem to generally attenuate the declines of farmland bird populations, but not to reverse them.
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