| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Sorensen, Charlotte, et al.
(författare)
-
Daytime Sleepiness, Apnea, Neuroimaging Correlates and Cortisol Dysregulation in a Memory Clinic Cohort
- 2024
-
Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Springer. - 2274-5807 .- 2426-0266.
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSleep disturbances as well as cortisol hypersecretion are increasingly acknowledged as risk factors for Alzheimer's disease (AD). However, the mechanisms underlying the association, and the interplay with cortisol abnormalities, remain unclear.ObjectivesThis study aims to identify how self-reported sleep disturbances are associated with structural brain measures and diurnal cortisol dysregulation among memory clinic patients.DesignA cross-sectional study performed at Karolinska University Hospital Memory Clinic, Sweden.ParticipantsThe study was based on 146 memory clinic patients diagnosed with either subjective cognitive impairment or mild cognitive impairment.MeasurementsSelf-reported sleep was measured using the Karolinska Sleep Questionnaire. MRI or CT was used to quantify structural brain measures using four visual rating scales (Scheltens, Pasquier, Koedam, and Fazekas scales), and salivary cortisol was sampled to measure diurnal cortisol patterns through measures of cortisol immediately after awakening, cortisol awakening response, bedtime cortisol, total cortisol from awakening to bedtime, and the AM/PM cortisol ratio.ResultsIncreased sleep apnea index (OR=1.20, 95% CI=1.04:1.39, p=0.015) was associated with greater odds of posterior brain atrophy, measured by the Koedam visual rating scale, and reduced awakening Cortisol (beta=-0.03, 95% CI=- 0.07:0.00, p=0.045). Increased daytime sleepiness was associated with both reduced awakening cortisol (beta=-0.03, 95% CI=-0.06:0.00, p=0.025) and a reduced AM/PM cortisol ratio (beta=-0.04, CI=-0.08:-0.01, p= 0.021).ConclusionIn a memory clinic cohort self-reported sleep disturbances are associated with both worse structural brain tissue integrity and altered diurnal cortisol profiles. These findings may add insights into possible mechanisms behind sleep disturbances in aging with subjective and cognitive impairment.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Sindi, S., et al.
(författare)
-
Multimodal Preventive Trial for Alzheimer’s Disease : MIND-ADmini Pilot Trial Study Design and Progress
- 2022
-
Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Serdi-Editions. - 2274-5807 .- 2426-0266. ; 9:1, s. 30-39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/ care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Anderson, M. E., et al.
(författare)
-
Evaluation of generic chiral liquid chromatography screens for pharmaceutical analysis
- 2003
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1005:02-jan, s. 83-101
-
Tidskriftsartikel (refereegranskat)abstract
- Two different automated generic liquid chromatography screens for the separation of chiral compounds of pharmaceutical interest have been evaluated. The test set comprised 53 chemically diverse chiral compounds involving 55 enantiomeric pairs from the pharmaceutical industry (i.e. starting materials, synthetic intermediates and drug substances). The first screen utilised four polysaccharide-based columns with five mobile phases and showed enantioselectivity for 87% of the test compounds. The second screen employed three macrocyclic glycopeptide columns with two mobile phases and showed enantioselectivity for 65% of the test compounds. Merging of the two screening procedures resulted in an enantioselectivity for 96% of the chiral compounds. It is anticipated that the systematic use of the automated chiral HPLC screens described in this report will substantially reduce the necessary time for method development of pharmaceutically related chiral analytical methods.
|
|
| 12. |
|
|
| 13. |
- Becher, Paul G., et al.
(författare)
-
Chemical signaling and insect attraction is a conserved trait in yeasts
- 2018
-
Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; , s. 2962-2974
-
Tidskriftsartikel (refereegranskat)abstract
- Yeast volatiles attract insects, which apparently is of mutual benefit, for both yeasts and insects. However, it is unknown whether biosynthesis of metabolites that attract insects is a basic and general trait, or if it is specific for yeasts that live in close association with insects. Our goal was to study chemical insect attractants produced by yeasts that span more than 250 million years of evolutionary history and vastly differ in their metabolism and lifestyle. We bioassayed attraction of the vinegar fly Drosophila melanogaster to odors of phylogenetically and ecologically distinct yeasts grown under controlled conditions. Baker's yeast Saccharomyces cerevisiae, the insect-associated species Candida californica, Pichia kluyveri and Metschnikowia andauensis, wine yeast Dekkera bruxellensis, milk yeast Kluyveromyces lactis, the vertebrate pathogens Candida albicans and Candida glabrata, and oleophilic Yarrowia lipolytica were screened for fly attraction in a wind tunnel. Yeast headspace was chemically analyzed, and co-occurrence of insect attractants in yeasts and flowering plants was investigated through a database search. In yeasts with known genomes, we investigated the occurrence of genes involved in the synthesis of key aroma compounds. Flies were attracted to all nine yeasts studied. The behavioral response to baker's yeast was independent of its growth stage. In addition to Drosophila, we tested the basal hexapod Folsomia candida (Collembola) in a Y-tube assay to the most ancient yeast, Y. lipolytica, which proved that early yeast signals also function on clades older than neopteran insects. Behavioral and chemical data and a search for selected genes of volatile metabolites underline that biosynthesis of chemical signals is found throughout the yeast clade and has been conserved during the evolution of yeast lifestyles. Literature and database reviews corroborate that yeast signals mediate mutualistic interactions between insects and yeasts. Moreover, volatiles emitted by yeasts are commonly found also in flowers and attract many insect species. The collective evidence suggests that the release of volatile signals by yeasts is a widespread and phylogenetically ancient trait, and that insect-yeast communication evolved prior to the emergence of flowering plants. Co-occurrence of the same attractant signals in yeast and flowers suggests that yeast-insect communication may have contributed to the evolution of insect-mediated pollination in flowers.
|
|
| 14. |
- Bloniecki, V, et al.
(författare)
-
Digital Screening for Cognitive Impairment - A Proof of Concept Study
- 2021
-
Ingår i: The journal of prevention of Alzheimer's disease. - : SERDI. - 2426-0266 .- 2274-5807. ; 8:2, s. 127-134
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Due to an ageing demographic and rapid increase of cognitive impairment and dementia, combined with potential disease-modifying drugs and other interventions in the pipeline, there is a need for the development of accurate, accessible and efficient cognitive screening instruments, focused on early-stage detection of neurodegenerative disorders. Objective: In this proof of concept report, we examine the validity of a newly developed digital cognitive test, the Geras Solutions Cognitive Test (GCST) and compare its accuracy against the Montreal Cognitive Assessment (MoCA). Methods: 106 patients, referred to the memory clinic, Karolinska University Hospital, due to memory complaints were included. All patients were assessed for presence of neurodegenerative disorder in accordance with standard investigative procedures. 66% were diagnosed with subjective cognitive impairment (SCI), 25% with mild cognitive impairment (MCI) and 9% fulfilled criteria for dementia. All patients were administered both MoCA and GSCT. Descriptive statistics and specificity, sensitivity and ROC curves were established for both test. Results: Mean score differed significantly between all diagnostic subgroups for both GSCT and MoCA (p<0.05). GSCT total test time differed significantly between all diagnostic subgroups (p<0.05). Overall, MoCA showed a sensitivity of 0.88 and specificity of 0.54 at a cut-off of <=26 while GSCT displayed 0.91 and 0.55 in sensitivity and specificity respectively at a cut-off of <=45. Conclusion: This report suggests that GSCT is a viable cognitive screening instrument for both MCI and dementia.
|
|
| 15. |
- Bloniecki, Victor, et al.
(författare)
-
The Geras Solutions Cognitive Test for Assessing Cognitive Impairment : Normative Data from a Population-Based Cohort
- 2023
-
Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Springer. - 2274-5807 .- 2426-0266. ; 2:10, s. 207-211
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is a need for the development of accurate, accessible and efficient screening instruments, focused on early-stage detection of neurocognitive disorders. The Geras Solutions cognitive test (GSCT) has showed potential as a digital screening tool for cognitive impairment but normative data are needed.Objective: The aim of this study was to obtain normative data for the GSCT in cognitively healthy patients, investigate the effects of gender and education on test scores as well as examine test-retest reliability.Methods: The population in this study consisted of 144 cognitively healthy subjects (MMSE>26) all at the age of 70 who were earlier included in the Healthy Aging Initiative Study conducted in Umea, Sweden. All patients conducted the GSCT and a subset of patients (n=32) completed the test twice in order to establish test-retest reliability.Results: The mean GSCT score was 46.0 (+/- 4.5) points. High level of education (>12 years) was associated with a high GSCT score (p = 0.02) while gender was not associated with GSCT outcomes (p = 0.5). GSCT displayed a high correlation between test and retest (r(30) = 0.8, p <0.01).Conclusion: This study provides valuable information regarding normative test-scores on the GSCT for cognitively healthy individuals and indicates education level as the most important predictor of test outcome. Additionally, the GSCT appears to display a good test-retest reliability further strengthening the validity of the test.
|
|
| 16. |
- Chakraborty, Amrita, et al.
(författare)
-
Yeast and fruit fly mutual niche construction and antagonism against mould
- 2022
-
Ingår i: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 36:7, s. 1639-1654
-
Tidskriftsartikel (refereegranskat)abstract
- A goal in insect–microbe ecology is to understand the mechanisms regulating species associations and mutualistic interactions. The spotted wing drosophila Drosophila suzukii develops in ripening fruit, unlike other drosophilids that typically feed on overripe fruit, and is associated with the yeast Hanseniaspora uvarum. We hypothesized that D. suzukii and H. uvarum engage in niche construction leading to a mutualistic relation, facilitating the exploitation of fruit and berries as larval substrate. We show that H. uvarum proliferates on both ripe and on unripe raspberries, mediates attraction of D. suzukii larvae and adult flies, enhances egg-laying in mated females and is a sufficient food substrate to support larval development. Moreover, H. uvarum suppresses the antagonistic grey mould, Botrytis cinerea in collaboration with D. suzukii larvae, and produces less ethanol than baker's yeast. H. uvarum thus creates favourable conditions for D. suzukii larval development, which is susceptible to ethanol and grey mould. D. suzukii, on the other hand, vectors H. uvarum to suitable substrates such as raspberries, where larval feeding activity enhances growth of H. uvarum. Larval feeding also helps to suppress B. cinerea, which otherwise outcompetes H. uvarum on raspberry, in the absence of fly larvae. In conclusion, H. uvarum enhances D. suzukii larval development on unripe berries, and D. suzukii promotes H. uvarum dispersal and growth on berries. Yeast and fly modify their shared habitat in reciprocal niche construction and mutual interaction. Read the free Plain Language Summary for this article on the Journal blog.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Hagman, Jennifer Ricci, et al.
(författare)
-
Use of a recombinant deacetylase to convert A1 red blood cells to the acquired B phenotype for quality control purposes
-
Ingår i: Blood Transfusion. - 1723-2007.
-
Tidskriftsartikel (refereegranskat)abstract
- Background - Correct blood group typing is the cornerstone of transfusion medicine. In patients whose gastrointestinal wall is compromised, bacterial enzymes can cause deacetylation of blood group A, converting N-acetylgalactosamine to galactosamine, which resembles the B-defining galactose. This acquired B (acqB) phenomenon, first described 1959, can lead to blood grouping errors. Herein, we explore the possibility of producing acqB red blood cells (RBCs) by enzymatic conversion, for quality control purposes.Materials and methods - A1 RBCs along with group B and O control RBCs were subjected to enzymatic digestion by bacterially derived deacetylase, FpGalNAcDeAc. RBCs were tested with monoclonal anti-A, anti-B, acquired-B-reactive anti-B (ES4 clone), and a panel of donor plasmas. Standard serological techniques were used. RBCs were subsequently frozen by a glycerolisation method, stored at −80 oC, and thawed for testing to evaluate stability.Results - Specific deacetylation of A antigen was achieved at both enzyme concentrations. Enzymatically modified A1 RBCs reacted 1-3+ with clone ES4 but not with other anti-B reagents. Group B and O RBC controls reacted as expected. Crossmatch testing revealed 1-3+ reactions in 17/26 group A plasma with modified RBCs but not with untreated controls. Furthermore, 2/3 group AB plasmas reacted strongly with the modified RBCs. The acqB phenotype was maintained upon freezing/thawing.Discussion - Using a recombinant deacetylase, we demonstrated the feasibility of creating acqB RBCs from donor A1 RBCs, thus providing a reagent for quality assurance of monoclonal anti-B. These RBCs can be frozen once treated, providing a reliable source of this unusual but clinically important phenotype.
|
|
| 22. |
- Hagman, Karl, et al.
(författare)
-
On the potential roles of ticks and migrating birds in the ecology of West Nile virus
- 2014
-
Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mosquitoes are the primary vectors of West Nile virus (WNV). Ticks have, however, been suggested to be potential reservoirs of WNV. In order to investigate their role in the spread of the virus, ticks, which had been collected from birds migrating northwards from Africa to Europe, were analyzed for the potential presence of WNV-RNA.METHODS: On the Mediterranean islands Capri and Antikythira a total of 14,824 birds were captured and investigated from which 747 ticks were collected.RESULTS AND CONCLUSION: Most of the identified ticks (93%) were nymphs and larvae of Hyalomma marginatum sensu lato, most of which were or appear to be Hyalomma rufipes. Of these ticks 729 were individually screened for WNV-RNA. None of the ticks was found to be WNV positive. Thus, there was no evidence that Hyalomma marginatum s.l. ticks play a role in the spread of WNV from Africa to Europe.
|
|
| 23. |
- Hagman, P. Olle G.
(författare)
-
Automatic quality sorting of Picea abies logs with a gamma ray log scanner
- 1993
-
Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 8:1-4, s. 583-590
-
Tidskriftsartikel (refereegranskat)abstract
- A quality index for quality sorting of Norway spruce (Picea abies) has been developed. The quality index expresses the expected mean quality of the centerboards from the log. This quality index is based on property variables obtained when using a gamma ray scanner. A multivariate calibration method, PLS (partial least squares models in latent variables), was used. A training set of 2 000 graded centerboards coming from 1 000 selected spruce logs was used to create the model between measured property variables and the expected quality output. The model is tested with crossvalidation within the training set, and expected precision of aim is 65% overall correct classification and a 70% correct classification for dimensions 150 to 225 mm. It can be utilized when sorting logs automatically with respect to the quality of the center boards.
|
|
| 24. |
- Hallgren, Line, et al.
(författare)
-
A First Attempt to Implement a Swirl Blade in Production of Ingots
- 2010
-
Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 50:12, s. 1763-1769
-
Tidskriftsartikel (refereegranskat)abstract
- Plant trials were carried out to test if it would be possible to place a ceramic swirl blade in the runner channel during filling of ingots The initial experiments showed that no production disturbances were found More specifically no problems with unusual refractory wear or cracks in the refractory were found Thus it was concluded that the use of swirl blade has a potential in the future to be used to influence the initial filling conditions Also mathematical modeling was done in order to illustrate how it was possible to improve the layout of the runner system in order to increase the potential for use of swirl for the current plant conditions The results showed that the meniscus was not dampened as much when the swirl blade is positioned in a horizontal direction in the runner channel compared to the results of a previous physical modeling study where the swirl blade was placed in a vertical direction just before the steel entered the mold However if a horizontally positioned swirl blade is used in combination with an inlet with an angle of 15 degrees the hump height at the initial filling stage can be lowered from 100 to 58 mm compared to a case without a swirl blade This illustrates the potential to apply mold powder closer to the bottom without risking reoxidation due to reactions with steel and mold powder
|
|
| 25. |
- Iregren, A, et al.
(författare)
-
Effects on the nervous system in different groups of workers exposed to aluminium
- 2001
-
Ingår i: Occupational and Environmental Medicine. ; 58, s. 453-60
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.METHODS - Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.RESULTS - The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.CONCLUSIONS - For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.
|
|
| 26. |
|
|
| 27. |
- Larsson, L. E., et al.
(författare)
-
Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population
- 2023
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press BV. - 1387-2877 .- 1875-8908. ; 96:2, s. 777-788
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sarcopenia and cognitive impairment are two leading causes of disabilities. Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. Methods: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.
|
|
| 28. |
|
|
| 29. |
- Leckner, Bo G, 1936, et al.
(författare)
-
Emissions from a 165 MWth FBC steam boiler
- 1992
-
Ingår i: Wirbelschichtsysteme 1992, VGB-TB214. ; :V28, s. 1-13
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Measurements of NO, N2O, SO2 and limestone utilization were measures on a 165 MW boiler as a function of bed temperature, excess air, and molar Ca/S ratio.
|
|
| 30. |
|
|
| 31. |
- Loren, N., et al.
(författare)
-
Fluorescence recovery after photobleaching in material and life sciences: putting theory into practice
- 2015
-
Ingår i: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 0033-5835 .- 1469-8994. ; 48:3, s. 323-387
-
Tidskriftsartikel (refereegranskat)abstract
- Fluorescence recovery after photobleaching (FRAP) is a versatile tool for determining diffusion and interaction/binding properties in biological and material sciences. An understanding of the mechanisms controlling the diffusion requires a deep understanding of structure-interaction-diffusion relationships. In cell biology, for instance, this applies to the movement of proteins and lipids in the plasma membrane, cytoplasm and nucleus. In industrial applications related to pharmaceutics, foods, textiles, hygiene products and cosmetics, the diffusion of solutes and solvent molecules contributes strongly to the properties and functionality of the final product. All these systems are heterogeneous, and accurate quantification of the mass transport processes at the local level is therefore essential to the understanding of the properties of soft (bio)materials. FRAP is a commonly used fluorescence microscopy-based technique to determine local molecular transport at the micrometer scale. A brief high-intensity laser pulse is locally applied to the sample, causing substantial photobleaching of the fluorescent molecules within the illuminated area. This causes a local concentration gradient of fluorescent molecules, leading to diffusional influx of intact fluorophores from the local surroundings into the bleached area. Quantitative information on the molecular transport can be extracted from the time evolution of the fluorescence recovery in the bleached area using a suitable model. A multitude of FRAP models has been developed over the years, each based on specific assumptions. This makes it challenging for the non-specialist to decide which model is best suited for a particular application. Furthermore, there are many subtleties in performing accurate FRAP experiments. For these reasons, this review aims to provide an extensive tutorial covering the essential theoretical and practical aspects so as to enable accurate quantitative FRAP experiments for molecular transport measurements in soft (bio)materials.
|
|
| 32. |
- Lorén, Niklas, 1970, et al.
(författare)
-
Fluorescence recovery after photobleaching in material and life sciences: Putting theory into practice
- 2015
-
Ingår i: Quarterly Reviews of Biophysics. - 1469-8994 .- 0033-5835. ; 48:3, s. 323-387
-
Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2015 Cambridge University Press.Fluorescence recovery after photobleaching (FRAP) is a versatile tool for determining diffusion and interaction/binding properties in biological and material sciences. An understanding of the mechanisms controlling the diffusion requires a deep understanding of structure-interaction-diffusion relationships. In cell biology, for instance, this applies to the movement of proteins and lipids in the plasma membrane, cytoplasm and nucleus. In industrial applications related to pharmaceutics, foods, textiles, hygiene products and cosmetics, the diffusion of solutes and solvent molecules contributes strongly to the properties and functionality of the final product. All these systems are heterogeneous, and accurate quantification of the mass transport processes at the local level is therefore essential to the understanding of the properties of soft (bio)materials. FRAP is a commonly used fluorescence microscopy-based technique to determine local molecular transport at the micrometer scale. A brief high-intensity laser pulse is locally applied to the sample, causing substantial photobleaching of the fluorescent molecules within the illuminated area. This causes a local concentration gradient of fluorescent molecules, leading to diffusional influx of intact fluorophores from the local surroundings into the bleached area. Quantitative information on the molecular transport can be extracted from the time evolution of the fluorescence recovery in the bleached area using a suitable model. A multitude of FRAP models has been developed over the years, each based on specific assumptions. This makes it challenging for the non-specialist to decide which model is best suited for a particular application. Furthermore, there are many subtleties in performing accurate FRAP experiments. For these reasons, this review aims to provide an extensive tutorial covering the essential theoretical and practical aspects so as to enable accurate quantitative FRAP experiments for molecular transport measurements in soft (bio)materials.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Nelson, D. W., et al.
(författare)
-
The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors
- 2022
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:6, s. 759-766
-
Tidskriftsartikel (refereegranskat)abstract
- Background: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health- systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. Methods: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. Results: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (similar to 4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. Conclusion: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.
|
|
| 36. |
- Nunn, A. D. G., et al.
(författare)
-
The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.
|
|
| 37. |
- Osterlund, P., et al.
(författare)
-
Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
-
Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Tengvall, Katarina, 1980-, et al.
(författare)
-
Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs
- 2016
-
Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundCanine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2.ResultsAdditional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10−7) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10−5), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region.ConclusionsOur experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Witzgall, Peter, et al.
(författare)
-
"This is not an Apple"-Yeast Mutualism in Codling Moth
- 2012
-
Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 1573-1561 .- 0098-0331. ; 38:8, s. 949-957
-
Tidskriftsartikel (refereegranskat)abstract
- The larva of codling moth Cydia pomonella (Tortricidae, Lepidoptera) is known as the worm in the apple, mining the fruit for food. We here show that codling moth larvae are closely associated with yeasts of the genus Metschnikowia. Yeast is an essential part of the larval diet and further promotes larval survival by reducing the incidence of fungal infestations in the apple. Larval feeding, on the other hand, enables yeast proliferation on unripe fruit. Chemical, physiological and behavioral analyses demonstrate that codling moth senses and responds to yeast aroma. Female moths are attracted to fermenting yeast and lay more eggs on yeast-inoculated than on yeast-free apples. An olfactory response to yeast volatiles strongly suggests a contributing role of yeast in host finding, in addition to plant volatiles. Codling moth is a widely studied insect of worldwide economic importance, and it is noteworthy that its association with yeasts has gone unnoticed. Tripartite relationships between moths, plants, and microorganisms may, accordingly, be more widespread than previously thought. It, therefore, is important to study the impact of microorganisms on host plant ecology and their contribution to the signals that mediate host plant finding and recognition. A better comprehension of host volatile signatures also will facilitate further development of semiochemicals for sustainable insect control.
|
|
| 47. |
- Zelan, Martin, 1981-, et al.
(författare)
-
Experimental measurement of efficiency and transport coherence of a cold-atom Brownian motor in optical lattices
- 2011
-
Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - : American Physical Society. - 1539-3755 .- 1550-2376. ; 83:2
-
Tidskriftsartikel (refereegranskat)abstract
- The rectification of noise into directed movement or useful energy is utilized by many different systems. The peculiar nature of the energy source and conceptual differences between such Brownian motor systems makes a characterization of the performance far from straightforward. In this work, where the Brownian motor consists of atoms interacting with dissipative optical lattices, we adopt existing theory and present experimental measurements for both the efficiency and the transport coherence. We achieve up to 0.3% for the efficiency and 0.01 for the Peclet number.
|
|
