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| 19. |
- Flisberg, Per, et al.
(författare)
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Skapa "tatueringsfri" stickkanal
- 2007
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Ingår i: Läkartidningen. - 0023-7205. ; 104:17, s. 1344-1344
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
- Johannesen, Kasper, 1982-
(författare)
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The value of evaluating and implementing pharmaceuticals
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pharmaceuticals are a central part of high-quality health care and a resource for improving population health. However, high prices set by private companies who develop and own the rights to new pharmaceuticals question the value that they contribute to the health care system. Publicly funded health care systems need to get the most from limited health care resources, which has become even more apparent in recent years with ageing populations, rapid technological development, and more recently the impact of COVID-19. Reducing pharmaceutical prices increase the current value that they offer to health care systems, but price reduction also decreases incentives to develop future treatments. Hence, the health care systems must balance the objective of improving the value from the treatments available today and incentivising the development of future treatments. Governments and health care decision makers use a variety of policies to control prices and use of pharmaceuticals. However, these policies are rarely the focus of formal analysis and their effect on short- and long-term population health is often unclear. The aim of this thesis was to investigate how policies that control pharmaceutical prices and implementation impact population health and incentives for pharmaceutical research and development (R&D). The first study in this thesis outlines a framework for assessing the effect of pharmaceutical policies on population health and pharmaceutical earnings and shows that price reducing policies can increase the current value of pharmaceuticals to health care systems while lowering R&D incentives. The design of specific policies determines the impact as well as the distribution of the gains of lower prices across patients, health care providers, pharmacies, and other affected parties. The second study analyses the trade-off between accuracy and cost of the cost-effectiveness appraisals for pharmaceuticals by viewing it as a diagnostic test that aims to identify costeffective treatments. The study identifies some policy relevant conclusions, including that the process should be flexible over time and depend on characteristics of the treatment undergoing assessment. Study three, investigating the impact of regional implementation variation of the antiplatelet ticagrelor, found that an additional 1,100 Quality Adjusted Life Years (QALYs) could have been gained from achieving equal implementation across health care regions. This represents a value of SEK 285 million from avoiding regional implementation variation of ticagrelor (given a value of SEK 250,000 per QALY). The study also shows that avoiding delays due to sequential decisions on reimbursement, treatment guidelines, and funding could have significant value. Finally, the fourth study investigates the comparative effectiveness of ticagrelor using observational data collected as part of routine clinical care in the SWEDEHEART registry. The study finds similar reduction in mortality as observed in the pivotal randomised clinical trial of ticagrelor, the PLATO trial. Furthermore, the importance of appropriate methods for observational research on comparative effectiveness are demonstrated, highlighting the importance of using appropriate methods when investigating the effectiveness of treatments used in clinical practice. In conclusion, this thesis shows the importance of analysing and understanding the effect of policies that control price and implementation of pharmaceuticals, whether the goal is to maximise the value from currently available pharmaceuticals or to also incentivise the development of new pharmaceuticals. Although the value of improving implementation may not be as obvious or tangible as savings from lowering pharmaceutical prices, improving implementation may contribute more to population health than reinvesting potential savings from price reductions.
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| 22. |
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| 23. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 24. |
- Lilja, Gisela, et al.
(författare)
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Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.
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| 25. |
- Norlin, Jenny, 1982-
(författare)
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Effectiveness and costs of new medical technologies : register-based research in psoriasis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis is a chronic, immunological and systemic disease with an estimated prevalence of about 2-3 percent. Psoriasis is associated with the joint disease psoriasis arthropathy. There are several treatments options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden.The overall objective of this thesis was to assess the relationship between Health Related Quality of Life (HRQOL) and clinical outcome measures in psoriasis patients, to analyse the effectiveness of biologics in psoriasis in everyday clinical practice and to explore how costs of the psoriasis population changed after the introduction of biologics in Sweden.Methods: Research was based on national administrative registers and PsoReg, the Swedish registry for systemic treatment of psoriasis. In a cross-sectional study (paper I) the three outcome measures: the generic HRQOL measure EQ-5D, the dermatology specific HRQOL measure the Dermatology Life Quality Index (DLQI) and the clinical measure of skin involvement, Psoriasis Area and Severity Index (PASI), were analysed by demographic characteristics. The generic EQ-5D among psoriasis patients was compared to previously published values for the general population in Sweden. Relationships between measures were examined with correlation tests and regression analysis. A longitudinal study included patients registered in PsoReg who switched to a biologic agent for the first time during registration (paper II). The three outcomes EQ-5D, DLQI, and PASI were analysed before and after switch in the overall patient group and in subgroups. The relative effectiveness of continuing with the standard care of conventional treatment compared to switching from standard care to biologics was analysed in patients with moderate to severe psoriasis (paper III). Patients in PsoReg were matched with propensity scores and average treatment effects were estimated. The estimated outcomes were the change of EQ-5D, DLQI, and PASI. Patients were identified in national registers at the National Board of Health and Welfare when analysing costs; either by a registration of a psoriasis diagnosis in the national patients register and/or by a registration in the prescribed drugs register of a topical treatment with calcipotriol, a substance which has the indication psoriasis only (paper IV). Direct costs included patients’ visits in specialist health care and prescribed drugs used for psoriasis treatment, retrieved from the national patients register and the prescribed drugs register, respectively. Indirect costs included productivity loss in terms of sick leave and disability pension, which estimated as excess costs compared to controls. Controls were selected from the normal population and matched on sex, age and municipality. Productivity loss was estimated based on data from the Longitudinal integration database for health insurance and labour market studies at Statistics Sweden.Results: Patients with moderate to severe psoriasis had significantly lower HRQOL in EQ-5D than the general population (paper I). Women rated their HRQOL lower than men, even though men had more severe clinical skin involvement than women. (paper I). The generic measure EQ-5D and the dermatology-specific DLQI had moderate correlations whereas EQ-5D had low correlation with the clinical measure PASI (paper I). Patients who switched to a biologic agent during registration in PsoReg had significant improvements in all outcomes (paper II). Patients who fulfilled the criteria for moderate to severe psoriasis had the highest benefits of the biologic agents (paper II). The matched conventionally and biologically treated patients with moderate to severe psoriasis were essentially equal in important observable variables (paper III). The subgroup of patients not responding to conventional treatment had high potential benefits of biologic agents (paper III). Individuals with psoriasis had sick leave and disability pension to a larger extent than their matched controls (paper IV). Direct costs increased, whereas the indirect costs of productivity loss decreased between 2006 and 2009 (paper IV).Conclusion: Psoriasis is associated both with direct costs and indirect costs, and it has a negative impact on patients’ HRQOL. When evaluating psoriasis treatments and making decisions about treatment guidelines, both generic, dermatology-specific HRQOL measures, and clinical measures are necessary; as they answer to different needs. Although dependent on data quality, generalisability, and current pricing, results suggest that conventional treatments are suitable as first line and biologic agents as second line treatment. Results indicate that the different types of systemic treatments are not allocated optimally among patients with psoriasis in Swedish clinical practice.
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| 26. |
- Nyberg, Jonna, 1967-, et al.
(författare)
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Distrust of Authorities : Experiences of Outcome and Processes of People Who Had Their Driving License Withdrawn Due to Visual Field Loss
- 2021
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Ingår i: Social Sciences. - : MDPI. - 2076-0760. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Citizens’ trust of authorities is of general importance, as it can affect trust in society as awhole. The Swedish Transport Agency is a state administrative authority responsible for drivinglicense withdrawal. If withdrawals are experienced as unfair by those affected, this might leadto decreased trust in the agency and in other actors involved. This study accordingly examineshow the experiences of people who have had their driving license for a private car withdrawndue to visual field loss might affect their distrust of the authorities, as related to outcomes andprocesses. Follow-up interviews were conducted with nine people from a previous study. Contentanalysis revealed one overarching theme, struggling for justice within a system perceived as unfair, whichcomprised four identified categories: preparedness for and understanding of the withdrawn driving license(WDL); perceptions of assessment methods, reactions and actions regarding the decision, and perceptions ofthe authorities’ performance. In sum, the vision tests on which withdrawals are based were perceivedas unfair, as they did not measure individual driving ability. Furthermore, rejections of appeals led tofeelings of hopelessness. Distrust regarding outcomes and processes related to the withdrawals wasalso fueled by experiences of deficiencies regarding, for example, performance and information.
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| 27. |
- Persson, Josefine, 1981, et al.
(författare)
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Long- term cost of spouses’ informal support for dependent midlife stroke survivors
- 2017
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Stroke is a major global disease that requires extensive care and support from society and relatives. The aim of this study was to identify and quantify the long- term informal support and to estimate the annual cost of informal support provided by spouses to their stroke surviving partner. Method: Data were based on the 7- year follow- up of the Sahlgrenska Academy Study on Ischemic Stroke. One- third of the spouses stated that they provided support to their stroke surviving partner. The magnitude of the support was assessed with a study- specific time- diary and was estimated for independent and dependent stroke survivors based on the scores of the modified Rankin Scale. To deal with skewed data, a two- part econometric model was used to estimate the annual cost of informal support. Result: Cohabitant dyads of 221 stroke survivors aged <70 at stroke onset were in- cluded in the study. Spouses of independent stroke survivors ( n = 188) provided on average 0.15 hr/day of practical support and 0.48 hr/day of being available. Corresponding figures for spouses of dependent stroke survivors ( n = 33) were 5.00 regarding practical support and 9.51 regarding being available. The mean annual cost of informal support provided for independent stroke survivors was estimated at €991 and €25,127 for dependent stroke survivor. Conclusion: The opportunity cost of informal support provided to dependent midlife stroke survivors is of a major magnitude many years after stroke onset and should be considered in economic evaluations of health care.
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| 28. |
- Persson, Josefine, 1981, et al.
(författare)
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Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors.
- 2017
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 26:11, s. 3059-3068
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses' QALY-weights. METHOD: Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses' QALY-weights. RESULT: Cohabitant dyads of 247 stroke survivors aged <70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses' QALY-weights. CONCLUSION: The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses' QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients' dependency would capture more of the total effect in dyads of stroke survivors.
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| 29. |
- Persson, Josefine, 1981, et al.
(författare)
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Stroke survivors’ long-term QALY-weights in relation to their spouses’ QALY-weights and informal support: a cross-sectional study
- 2017
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Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Healthcare interventions that have positive effects on the stroke survivors’ health-related quality of Life (HRQoL) and quality-adjusted life-years (QALYs) might also have positive effects for their spouses in terms of improved HRQoL and/or reduced spousal informal support. However, knowle dge about stroke survivors ’ HRQoL and QALY and the consequences for their spouses’ HRQoL and QALY is limited. Therefore, the aim of this study was to describe the HRQoL and QALY-weights in dyads of stroke survivors in comparison with dyads of healthy controls, and to study the relationship between the stroke survivors’ QALY-weights and consequences for spouses in terms of QALY-weight and annual cost of informal support, using a long-term perspective. Methods: Data on stroke survivors, controls, and spouses were collected from the seven-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). HRQoL was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. The magnitude of the support was assessed with a study specific time-diary. An ordinary least squares (OLS) regression was used to estimate the association between stroke survivors’ and spouses’ QALY-weights. A two-part econometri c model was used to estimate the association between stroke survivors’ QALY-weights and the time spent and cost of spouses’ informal support. Results: Cohabitant dyads of 248 stroke survivors’ aged <70 at stroke onset and 245 controls were included in the study. Stroke survivors had lower HRQoL in the SF-36 domains physical functioning, physical role, general health, vitality (P <0.001), and social functioning (P = 0.005) in comparison with their cohabitant spouses. There was no significant difference in HRQoL for the dyads of controls. The results from the regression analyses showed that lo wer QALY-weights of the stroke survivors were associated with lower QALY-weights of their spouses and increased annual cost of spousal informal support. Conclusion: Our results show that the QALY-weight s for stroke surv ivors had consequences for their spouses in terms of annual cost of spousal informal support and QALY-weights. Hence, economic evalu ation of interventions that improve the HRQoL of the stroke survivors but ignore the consequences for their spouses may underestimate the value of the intervention.
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| 30. |
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| 31. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 32. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 33. |
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| 34. |
- TIGERSTRÖM, ANNA KATARINA, 1976, et al.
(författare)
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Functional split and crosslinking of the membrane domain of the beta subunit of proton-translocating transhydrogenase from Escherichia coli
- 2003
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 42, s. 10998-11003
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Tidskriftsartikel (refereegranskat)abstract
- Proton pumping nicotinamide nucleotide transhydrogenase from Escherichia coli contains an alpha subunit with the NAD(H)-binding domain I and a beta subunit with the NADP(H)-binding domain III. The membrane domain (domain II) harbors the proton channel and is made up of the hydrophobic parts of the alpha and beta subunits. The interface in domain II between the alpha and the beta subunits has previously been investigated by cross-linking loops connecting the four transmembrane helices in the alpha subunit and loops connecting the nine transmembrane helices in the beta subunit. However, to investigate the organization of the nine transmembrane helices in the beta subunit, a split was introduced by creating a stop codon in the loop connecting transmembrane helices 9 and 10 by a single mutagenesis step, utilizing an existing downstream start codon. The resulting enzyme was composed of the wild-type alpha subunit and the two new peptides beta1 and beta2. As compared to other split membrane proteins, the new transhydrogenase was remarkably active and catalyzed activities for the reduction of 3-acetylpyridine-NAD(+) by NADPH, the cyclic reduction of 3-acetylpyridine-NAD(+) by NADH (mediated by bound NADP(H)), and proton pumping, amounting to about 50-107% of the corresponding wild-type activities. These high activities suggest that the alpha subunit was normally folded, followed by a concerted folding of beta1 + beta2. Cross-linking of a betaS105C-betaS237C double cysteine mutant in the functional split cysteine-free background, followed by SDS-PAGE analysis, showed that helices 9, 13, and 14 were in close proximity. This is the first time that cross-linking between helices in the same beta subunit has been demonstrated.
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| 35. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 92:3
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Tidskriftsartikel (refereegranskat)
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| 36. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Aad, G., et al.
(författare)
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- 2012
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Ingår i: Nuclear Physics, Section B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 864:3, s. 341-381
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 92:3
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Aad, G., et al.
(författare)
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- 2013
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Tidskriftsartikel (refereegranskat)
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| 40. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 41. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 91:11, s. 112011-
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| 42. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 92:1
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Tidskriftsartikel (refereegranskat)
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| 43. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 44. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Aad, G, et al.
(författare)
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- 2014
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 113:17
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Tidskriftsartikel (refereegranskat)
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