| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Berndt, Carsten, et al.
(författare)
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Ascorbate and endocytosed Motexafin gadolinium induce lysosomal rupture.
- 2011
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 307:2, s. 119-23
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Tidskriftsartikel (refereegranskat)abstract
- Motexafin gadolinium (MGd) sensitizes malignant cells to ionizing radiation, although the underlying mechanisms for uptake and sensitization are both unclear. Here we show that MGd is endocytosed by the clathrin-dependent pathway with ensuing lysosomal membrane permeabilization, most likely via formation of reactive oxygen species involving redox-active metabolites, such as ascorbate. We propose that subsequent apoptosis is a synergistic effect of irradiation and high MGd concentrations in malignant cells due to their pronounced endocytic activity. The results provide novel insights into the mode of action of this promising anti-cancer drug, which is currently under clinical trials.
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| 3. |
- Daníelsdóttir, Hilda Björk, et al.
(författare)
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Adverse Childhood Experiences and Adult Mental Health Outcomes
- 2024
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 81:6, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders.OBJECTIVE: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding.DESIGN, SETTING, AND PARTICIPANTS: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023.EXPOSURES: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey.MAIN OUTCOMES AND MEASURES: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register.RESULTS: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11).CONCLUSIONS AND RELEVANCE: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.
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| 4. |
- Delacour, Delphine, et al.
(författare)
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Apical sorting by galectin-3-dependent glycoprotein clustering
- 2007
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Ingår i: Traffic: the International Journal of Intracellular Transport. - : Wiley. - 1398-9219. ; 8:4, s. 379-388
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells are characterized by their polarized organization based on an apical membrane that is separated from the basolateral membrane domain by tight junctions. Maintenance of this morphology is guaranteed by highly specific sorting machinery that separates lipids and proteins into different carrier populations for the apical or basolateral cell surface. Lipid-raft-independent apical carrier vesicles harbour the beta-galactoside-binding lectin galectin-3, which interacts directly with apical cargo in a glycan-dependent manner. These glycoproteins are mistargeted to the basolateral membrane in galectin-3-depleted cells, dedicating a central role to this lectin in raft-independent sorting as apical receptor. Here, we demonstrate that high-molecular-weight clusters are exclusively formed in the presence of galectin-3. Their stability is sensitive to increased carbohydrate concentrations, and cluster formation as well as apical sorting are perturbed in glycosylation-deficient Madin-Darby canine kidney (MDCK) II cells. Together, our data suggest that glycoprotein cross-linking by galectin-3 is required for apical sorting of non-raft-associated cargo.
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| 5. |
- Johannes, Ludger, et al.
(författare)
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Galectins at a glance
- 2018
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 131:9
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are carbohydrate-binding proteins that are involved in many physiological functions, such as inflammation, immune responses, cell migration, autophagy and signalling. They are also linked to diseases such as fibrosis, cancer and heart disease. How such a small family of only 15 members can have such widespread effects remains a conundrum. In this Cell Science at a Glance article, we summarise recent literature on the many cellular activities that have been ascribed to galectins. As shown on the accompanying poster, these include carbohydrate-independent interactions with cytosolic or nuclear targets and carbohydrate-dependent interactions with extracellular glycoconjugates. We discuss how these intra- and extracellular activities might be linked and point out the importance of unravelling molecular mechanisms of galectin function to gain a true understanding of their contributions to the physiology of the cell. We close with a short outlook on the organismal functions of galectins and a perspective on the major challenges in the field.
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| 6. |
- Klink, Jacob, et al.
(författare)
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Thermal fault detection by changes in electrical behaviour in lithium-ion cells
- 2021
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Ingår i: Journal of Power Sources. - : Elsevier. - 0378-7753 .- 1873-2755. ; 490
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Tidskriftsartikel (refereegranskat)abstract
- With this paper a method to detect faults of lithium-ion cells during operation is first presented and later validated by experiment. Since every cell fault will increase the cell temperature towards its process until thermal runaway the method uses the temperature-dependent change of the cell impedance as fault feature. Using a 46 Ah pouch cell the model was parameterised by electrochemical impedance spectroscopy and then validated during dynamic load. For this purpose the Worldwide harmonised Light vehicles Test Procedure (WLTP) was chosen. The presence of a fault was simulated by heating the cell once uniformly and once locally and the progression of the chosen fault feature analysed. For both test cases the method proposed was able to detect the present heat source before the thermal runaway was triggered and venting or voltage drop were observed.
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| 7. |
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| 8. |
- Lauber, Chris, et al.
(författare)
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Deciphering the Origin and Evolution of Hepatitis B Viruses by Means of a Family of Non-enveloped Fish Viruses
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 22:3, s. 387-399,e1-e6
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B viruses (HBVs), which are enveloped viruses with reverse-transcribed DNA genomes, constitute the family Hepadnaviridae. An outstanding feature of HBVs is their streamlined genome organization with extensive gene overlap. Remarkably, the similar to 1,100 bp open reading frame (ORF) encoding the envelope proteins is fully nested within the ORF of the viral replicase P. Here, we report the discovery of a diversified family of fish viruses, designated nackednaviruses, which lack the envelope protein gene, but otherwise exhibit key characteristics of HBVs including genome replication via proteinprimed reverse-transcription and utilization of structurally related capsids. Phylogenetic reconstruction indicates that these two virus families separated more than 400 million years ago before the rise of tetrapods. We show that HBVs are of ancient origin, descending from non-enveloped progenitors in fishes. Their envelope protein gene emerged de novo, leading to a major transition in viral lifestyle, followed by co-evolution with their hosts over geologic eras.
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| 9. |
- Leissner, Johanna, et al.
(författare)
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Climate for Culture : assessing the impact of climate change on the future indoor climate in historic buildings using simulations
- 2015
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Ingår i: Heritage Science. - : Springer Science and Business Media LLC. - 2050-7445. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background The present study reports results from the large-scale integrated EU project "Climate for Culture". The full name, or title, of the project is Climate for Culture: damage risk assessment, economic impact and mitigation strategies for sustainable preservation of cultural heritage in times of climate change. This paper focusses on implementing high resolution regional climate models together with new building simulation tools in order to predict future outdoor and indoor climate conditions. The potential impact of gradual climate change on historic buildings and on the vast collections they contain has been assessed. Two moderate IPCC emission scenarios A1B and RCP 4.5 were used to predict indoor climates in historic buildings from the recent past until the year 2100. Risks to the building and to the interiors with valuable artifacts were assessed using damage functions. A set of generic building types based on data from existing buildings were used to transfer outdoor climate conditions to indoor conditions using high resolution climate projections for Europe and the Mediterranean. Results The high resolution climate change simulations have been performed with the regional climate model REMO over the whole of Europe including the Mediterranean region. Whole building simulation tools and a simplified building model were developed for historic buildings; they were forced with high resolution climate simulations. This has allowed maps of future climate-induced risks for historic buildings and their interiors to be produced. With this procedure future energy demands for building control can also be calculated. Conclusion With the newly developed method described here not only can outdoor risks for cultural heritage assets resulting from climate change be assessed, but also risks for indoor collections. This can be done for individual buildings as well as on a larger scale in the form of European risk maps. By using different standardized and exemplary artificial buildings in modelling climate change impact, a comparison between different regions in Europe has become possible for the first time. The methodology will serve heritage owners and managers as a decision tool, helping them to plan more effectively mitigation and adaption measures at various levels.
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| 10. |
- Ludewig, Kristin, et al.
(författare)
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Phenology and morphology of the invasive legume Lupinus polyphyllus along a latitudinal gradient in Europe
- 2022
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Ingår i: NeoBiota. - : Pensoft Publishers. - 1619-0033 .- 1314-2488. ; 78
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Tidskriftsartikel (refereegranskat)abstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distributionranges. Temperature is one of the most important drivers of plant phenology together with day length.The adaptation of their phenology may be important for the success of invasive plant species. The presentstudy aims at understanding how the performance and the phenology of the invasive legume Lupinuspolyphyllus vary with latitude. We sampled data across a >2000 km latitudinal gradient from Centralto Northern Europe. We quantified variation in phenology of flowering and fruiting of L. polyphyllususing >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 sites. Theday of the year at which different phenological phases were reached, increased 1.3–1.8 days per degreelatitude, whereas the growing degree days (gdd) required for these phenological phases decreased 5–16 gddper degree latitude. However, this difference disappeared, when the day length of each day included inthe calculation of gdd was considered. The day of the year of the earliest and the latest climatic zone toreach any of the three studied phenological phases differed by 23–30 days and temperature requirementsto reach these stages differed between 62 and 236 gdd. Probably, the invasion of this species will furtherincrease in the northern part of Europe over the next decades due to climate warming. For invasive speciescontrol, our results suggest that in countries with a large latitudinal extent, the mowing date should shiftby ca. one week per 500 km at sites with similar elevations.
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