| 1. |
- Båth, Petra, 1988, et al.
(författare)
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Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
- 2022
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Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 78, s. 698-708
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Tidskriftsartikel (refereegranskat)abstract
- Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 angstrom resolution when exposed to XFEL radiation, which is an improvement of 0.15 angstrom over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile Q(B) pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
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| 2. |
- Edlund, Petra, et al.
(författare)
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The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
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| 3. |
- Bukartė, Eglė, et al.
(författare)
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Dynamic band-shift signal in two-dimensional electronic spectroscopy: A case of bacterial reaction center
- 2021
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 154:11
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Tidskriftsartikel (refereegranskat)abstract
- Optical nonlinear spectroscopies carry a high amount of information about the systems under investigation; however, as they report polarization signals, the resulting spectra are often congested and difficult to interpret. To recover the landscape of energy states and physical processes such as energy and electron transfer, a clear interpretation of the nonlinear signals is prerequisite. Here, we focus on the interpretation of the electrochromic band-shift signal, which is generated when an internal electric field is established in the system following optical excitation. Whereas the derivative shape of the band-shift signal is well understood in transient absorption spectroscopy, its emergence in two-dimensional electronic spectroscopy (2DES) has not been discussed. In this work, we employed 2DES to follow the dynamic band-shift signal in reaction centers of purple bacteria Rhodobacter sphaeroides at 77 K. The prominent two-dimensional derivative-shape signal appears with the characteristic formation time of the charge separated state. To explain and characterize the band-shift signal, we use expanded double-sided Feynman diagram formalism. We propose to distinguish two types of Feynman diagrams that lead to signals with negative amplitude: excited state absorption and re-excitation. The presented signal decomposition and modeling analysis allows us to recover precise electrochromic shifts of accessory bacteriochlorophylls, identify additional signals in the B band range, and gain a further insight into the electron transfer mechanism. In a broader perspective, expanded Feynman diagram formalism will allow for interpretation of all 2D signals in a clearer and more intuitive way and therefore facilitate studying the underlying photophysics.
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| 4. |
- Edlund, Charlotta, et al.
(författare)
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The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota : a randomised multicentre clinical trial in Sweden
- 2022
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Ingår i: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 22:3, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI).METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15).FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug.INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens.
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| 5. |
- Ghosh, Swagatha, 1987, et al.
(författare)
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A simple goniometer-compatible flow cell for serial synchrotron X-ray crystallography
- 2023
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Ingår i: Journal of Applied Crystallography. - : International Union of Crystallography (IUCr). - 1600-5767. ; 56, s. 449-460
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography was initially developed for roomtemperature X-ray diffraction studies of macromolecules at X-ray free electron lasers. When combined with tools that initiate biological reactions within microcrystals, time-resolved serial crystallography allows the study of structural changes that occur during an enzyme catalytic reaction. Serial synchrotron X-ray crystallography (SSX), which extends serial crystallography methods to synchrotron radiation sources, is expanding the scientific community using serial diffraction methods. This report presents a simple flow cell that can be used to deliver microcrystals across an X-ray beam during SSX studies. This device consists of an X-ray transparent glass capillary mounted on a goniometercompatible 3D-printed support and is connected to a syringe pump via lightweight tubing. This flow cell is easily mounted and aligned, and it is disposable so can be rapidly replaced when blocked. This system was demonstrated by collecting SSX data at MAX IV Laboratory from microcrystals of the integral membrane protein cytochrome c oxidase from Thermus thermophilus, from which an X-ray structure was determined to 2.12 angstrom resolution. This simple SSX platform may help to lower entry barriers for non-expert users of SSX.
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| 6. |
- Ghosh, Swagatha, et al.
(författare)
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A simple goniometer-compatible flow cell for serial synchrotron X-ray crystallography
- 2023
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Ingår i: Journal of Applied Crystallography. - 0021-8898. ; 56:Pt 2, s. 449-460
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography was initially developed for room-temperature X-ray diffraction studies of macromolecules at X-ray free electron lasers. When combined with tools that initiate biological reactions within microcrystals, time-resolved serial crystallography allows the study of structural changes that occur during an enzyme catalytic reaction. Serial synchrotron X-ray crystallography (SSX), which extends serial crystallography methods to synchrotron radiation sources, is expanding the scientific community using serial diffraction methods. This report presents a simple flow cell that can be used to deliver microcrystals across an X-ray beam during SSX studies. This device consists of an X-ray transparent glass capillary mounted on a goniometer-compatible 3D-printed support and is connected to a syringe pump via lightweight tubing. This flow cell is easily mounted and aligned, and it is disposable so can be rapidly replaced when blocked. This system was demonstrated by collecting SSX data at MAX IV Laboratory from microcrystals of the integral membrane protein cytochrome c oxidase from Thermus thermophilus, from which an X-ray structure was determined to 2.12 Å resolution. This simple SSX platform may help to lower entry barriers for non-expert users of SSX.
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| 7. |
- Hassan, Jasmin, et al.
(författare)
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Reference standards for follicular density in ovarian cortex from birth to sexual maturity
- 2023
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:4
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Tidskriftsartikel (refereegranskat)abstract
- Research question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean +/- SD 11 +/- 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.Results: No difference was observed between Z-scores in samples from untreated patients (0.3 +/- 3.5, n = 30) and patients treated with (0.5 +/- 2.9, n = 48) and without (0.1 +/- 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 +/- 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 +/- 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 +/- 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 +/- 4.2 versus 10.7 +/- 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009).Conclusion: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
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| 8. |
- Lundström, Petra, et al.
(författare)
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A Three Year Case Study with a Multidisciplinary Treatment of Relative Energy Deficiency and Anorexia in a Female Tennis Player
- 2020
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Ingår i: Annals of Sports Medicine and Research. - 2379-0571. ; 7:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Tennis is an all-year racket sport requiring qualities such as speed, agility, flexibility, and endurance, as competitions may last up to five hours.Elite players have an estimated daily need of carbohydrate (CHO) between 6-10 g/kg to sustain high amounts of training and frequent competitions. Low energy availability (LEA), over time, may impair both health and performance. LEA may cause metabolic suppression and altered hormone levels via hypothalamic–pituitary– gonadal axis (HPG). Female athletes with LEA have an increased risk of developing menstrual dysfunction, low bone mineral density (BMD), disordered eating behavior (DE) and an eating disorder (ED). This article provides a case-study of an internationally ranked female tennis player, with a recent performance-driven weight loss of 11 kg. She was diagnosed with functional hypothalamic primary amenorrhea (FHA) and anorexia nervosa (AN). The predetermined goal was to return to play and the treatment was based on the guidelines for relative Energy Deficiency in Sport (REDS-CAT). After three years of multidisciplinary interventions, the athlete safely returned to play. Her weight and body composition improved, her menstrual cycle was normalized and the diagnostically scores of AN indicated non-clinical significance. The multidisciplinary treatment enabled the athlete to return to play despite several years of LEA and AN.
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| 9. |
- Nordin-Bates, Sanna M., et al.
(författare)
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Evaluation of DancExcellent, a Combined CBT and Nutrition Education Intervention
- 2023
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Ingår i: Medical problems of performing artists. - : SCIENCE & MEDICINE INC. - 0885-1158 .- 1938-2766. ; 38:2, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disordered eating (DE) behaviors are relatively common among high-level dancers, especially in classical ballet. At the same time, interventions aimed at reducing DE behaviors in this population are scarce. METHODS: An 8-week exploratory preventive interven-tion for DE behaviors was carried out in a high-level ballet school for 40 teenagers aged 12-15 years (77.5% female). Both risk factors (perfectionism) and potentially protective factors (self-esteem, self-compassion) for the development of DE behaviors were considered. The intervention was created specifically for this study and consisted of five cognitive behavior therapy (CBT) work-shops and four nutrition workshops. Additional compo-nents included newsletters for pupils and educational sessions and social media interactions with staff and parents. The intervention comprised two phases (control and intervention periods), with students acting as their own controls. Standardized questionnaires were com-pleted before and after both phases. RESULTS: Ques-tionnaire results did not indicate any changes in reported perfectionism, self-esteem, or self-compassion, nor were symptoms of DE affected during either the control or intervention periods. CONCLUSIONS: The intervention did not yield any discernible impact. How - ever, it was affected by the onset of the COVID-19 pan-demic, which limits our ability to draw conclusions about intervention effectiveness. Evaluations with pupils offer several considerations for future improvements.
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| 10. |
- Nordin-Bates, Sanna, et al.
(författare)
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Preventing Disordered Eating in Teenage Ballet Students : Evaluation of DancExcellent, a Combined CBT and Nutrition Education Intervention
- 2023
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Ingår i: Medical problems of performing artists. - : Science & Medicine Inc. - 0885-1158 .- 1938-2766. ; 38:2, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disordered eating (DE) behaviors are relatively common among high-level dancers, especially in classical ballet. At the same time, interventions aimed at reducing DE behaviors in this population are scarce. METHODS: An 8-week exploratory preventive interven-tion for DE behaviors was carried out in a high-level ballet school for 40 teenagers aged 12-15 years (77.5% female). Both risk factors (perfectionism) and potentially protective factors (self-esteem, self-compassion) for the development of DE behaviors were considered. The intervention was created specifically for this study and consisted of five cognitive behavior therapy (CBT) work-shops and four nutrition workshops. Additional compo-nents included newsletters for pupils and educational sessions and social media interactions with staff and parents. The intervention comprised two phases (control and intervention periods), with students acting as their own controls. Standardized questionnaires were com-pleted before and after both phases. RESULTS: Ques-tionnaire results did not indicate any changes in reported perfectionism, self-esteem, or self-compassion, nor were symptoms of DE affected during either the control or intervention periods. CONCLUSIONS: The intervention did not yield any discernible impact. How - ever, it was affected by the onset of the COVID-19 pan-demic, which limits our ability to draw conclusions about intervention effectiveness. Evaluations with pupils offer several considerations for future improvements. Med Probl Perform Art 2023;38(2):71-79.
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