| 1. |
- Fodje, Michel, et al.
(författare)
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Interplay Between an AAA Module and an Integrin I Domain May Regulate the Function of Magnesium Chelatase
- 2001
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 311:1, s. 111-122
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Tidskriftsartikel (refereegranskat)abstract
- In chlorophyll biosynthesis, insertion of Mg2+ into protoporphyrin IX is catalysed in an ATP-dependent reaction by a three-subunit (BchI, BchD and BchH) enzyme magnesium chelatase. In this work we present the three-dimensional structure of the ATP-binding subunit BchI. The structure has been solved by the multiple wavelength anomalous dispersion method and refined at 2.1 A resolution to the crystallographic R-factor of 22.2 % (Rfree = 24.5 %). It belongs to the chaperone-like ''ATPase associated with a variety of cellular activities'' (AAA) family of ATPases, with a novel arrangement of domains: the C-terminal helical domain is located behind the nucleotide-binding site, while in other known AAA module structures it is located on the top. Examination by electron microscopy of BchI solutions in the presence of ATP demonstrated that BchI, like other AAA proteins, forms oligomeric ring structures. Analysis of the amino acid sequence of subunit BchD revealed an AAA module at the N-terminal portion of the sequence and an integrin I domain at the C terminus. An acidic, proline-rich region linking these two domains is suggested to contribute to the association of BchI and BchD by binding to a positively charged cleft at the surface of the nucleotide-binding domain of BchI. Analysis of the amino acid sequences of BchI and BchH revealed integrin I domain-binding sequence motifs. These are proposed to bind the integrin I domain of BchD during the functional cycle of magnesium chelatase, linking porphyrin metallation by BchH to ATP hydrolysis by BchI. An integrin I domain and an acidic and proline-rich region have been identified in subunit CobT of cobalt chelatase, clearly demonstrating its homology to BchD. These findings, for the first time, provide an insight into the subunit organisation of magnesium chelatase and the homologous colbalt chelatase.
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| 2. |
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Biobanks as resources for health
- 2003
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Ingår i: Biobanks as Resources for Health. - : Uppsala University. - 9150616595 ; , s. 9-20
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Gustafsson Stolt, Ulrica, 1965-
(författare)
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Aspects in bioethics : Theory and practice in a preventive screening for type 1 diabetes
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- From a clinical perspective, as well as societal and global, the present rapid increase in the number of people diagnosed with diabetes is a cause of great concern. Simultaneously, our understanding of the aetiology and pathogenesis of type 1 diabetes (IDDM) remain limited. As of now there are two main approaches to predict the risk of diabetes development: either before by assessing the genetic factors presumably involved, or after by a combination of immunological (IAA, la-2, GAD) and genetic typing. The problems are for example that only 10% of those that develop diabetes have a first-degree relative, and that only a proportion of those with a genetic susceptibility will eventually develop type 1 diabetes Theoretically, prevention of type 1 diabetes can be done at three different levels: primary, secondary and tertiary intervention. However, it is argued that more basic research is needed before effective and safe prevention of type 1 can be introduced. More effort is also needed to identify the environmental factors and potential triggers.Screening for pre-diabetes belong to one of the two type of genetic testing and screening who are generally considered being ethically controversial: predictive, pre-symptomatic testing of children for disorders that do not usually (or where there are uncertainty in progression rate) manifest until adult life, and for which an effective intervention measure is not available. There are risks for creation of distress and anxiety, risks for false-positive results, risks of bypassing informed consent and stigmatisation in case of potential positive results. Discussed are also issues concerning the upholding of individual autonomy, confidentiality and integrity. Simultaneously, it has been argued that the ethical discussion is based on empirical premises that are not sufficiently studied, and that we furthermore lack empirical data.Thematically this thesis belongs to the discipline of descriptive ethics. Our aim was to empirically explore and describe the attitudes and opinions of to, on the basis of the empirical results, point at and discuss issues of bioethical relevance. Our case was ABIS (All Babies In Southeast Sweden) an ongoing prospective longitudinal cohort study for the prediction and prevention of type 1 diabetes (n=17,005). The research design included both qualitative studies: interviews with participating and non-participating mothers, as well as health professionals involved, and a quantitative study: consisting of a designed questionnaire exploring bioethical issues.The interview data indicate a positive attitude both to the ABIS aims and methods and there were less concern over research material, screening results, prevention than often assumed. However, there were concern expressed of issues concerning confidentiality, integrity and restrictions. The reasons for declining participation varied: not wanting their child put through frequent blood testing, fear of "experimentation". The interviews with the staff involved gave important data regarding information procedures and research design, for example the importance of identifying and informing all actors in research involving humans. The questionnaire data support at large earlier empirical findings: a benevolent attitude, less concern over biological samples and written material. Similar concerns were raised of confidentiality and integrity: material used to initial purposes, protection of identity, renewed consent. The majority wanted to know about high-risk status, even though no available intervention. Our interest in information and informed consent was renewed since participants showed a lack of knowledge/understanding regarding basic aims and methods. The problem of informed consent was discussed in the last two papers: the first focusing on the problem of obtaining informed consent, while the second explored potential alternatives of action if we have reason to believe the participants lack a sufficient understanding.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Hansson, Mats G.
(författare)
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Värderingars värde
- 2000
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Ingår i: Det givna och det föränderliga. - : Nya Doxa, Nora. ; , s. 89-
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Lidén, Annika, et al.
(författare)
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Genetic counselling for cancer and risk perception
- 2003
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 42:7, s. 726-734
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Tidskriftsartikel (refereegranskat)abstract
- The main aim was to investigate risk perception and psychological distress in individuals attending genetic counselling. A consecutive series of 86 individuals with a diagnosis and/or family history of breast, ovarian or colorectal cancer was included. Risk assessments were performed before and immediately after genetic counselling and at a one-year follow-up. Psychological distress was assessed 1 week before, and 6 weeks, 6 months and 1 year after genetic counselling. The number of individuals who correctly-estimated the general risk in the population increased significantly from 35%, before to 82% after counselling (p < 0.001). One year later, data on general risk estimates showed a significant reduction of the number of correct estimations to 51%, compared with directly after the counselling (p < 0.005). In total, 54% estimated their own lifetime risk correctly after the counselling, compared with 17% before (p < 0.001) (those with a cancer diagnosis estimated the risk of their children developing cancer). One year later, the number of correct estimations had dropped to 28%. Before the counselling, the majority of the participants overestimated both the general risk and their own/children's risk. The participants experienced moderate levels of psychological distress before the counselling and a decrease of anxiety afterwards (p < 0.02). However, half of the participants reported moderate or high distress. There were no differences in psychological distress between those who estimated their risk/ children's risk as low, moderate or high or between those who over-, under- or correctly estimated their own/children's risk. Further investigations are needed to develop and adjust the risk information provided to the individual in order to avoid misunderstanding, especially as this information is going to be revealed to family members Counselling support should be offered to those individuals who experience psychological distress.
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