| 1. |
- de Winter, J M, et al.
(författare)
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KBTBD13 is an actin-binding protein that modulates muscle kinetics
- 2020
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Ingår i: Journal of Clinical Investigation. - : Stanford University Press. - 0021-9738 .- 1558-8238. ; 130:2, s. 754-767
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow muscle relaxation, compromising contractility and daily life activities. The role of KBTBD13 in muscle is unknown, and the pathomechanism underlying NEM6 is undetermined. A combination of transcranial magnetic stimulation-induced muscle relaxation, muscle fiber- and sarcomere-contractility assays, low-angle x-ray diffraction, and superresolution microscopy revealed that the impaired muscle-relaxation kinetics in NEM6 patients are caused by structural changes in the thin filament, a sarcomeric microstructure. Using homology modeling and binding and contractility assays with recombinant KBTBD13, Kbtbd13-knockout and Kbtbd13(R408c)-knockin mouse models, and a GFP-labeled Kbtbd13-transgenic zebrafish model, we discovered that KBTBD13 binds to actin - a major constituent of the thin filament - and that mutations in KBTBD13 cause structural changes impairing muscle-relaxation kinetics. We propose that this actin-based impaired relaxation is central to NEM6 pathology.
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| 2. |
- Aarts, B., et al.
(författare)
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DNActivity: International cooperation in activity level interpretation of forensic DNA evidence.
- 2015
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Ingår i: Abstract book, 7<sup>th</sup> European Academy of Forensic Science, EAFS, Prag, Tjeckien, 2015.. ; , s. 555-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activitity level (i.e. ‘how did the DNA get there?’). The answers to these questions are usually formulated as the probability of the evidence under alternative scenarios. As activity level questions are part of investigative and legal considerations it is of paramount importance that expert witnesses are provided with knowledge and tools to address these questions.To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects. There is a paucity of empirical data on these topics, but the number of studies is increasing both through in-house experiments and experimental data published in international scientific journals.Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.Moreover, if existing data and data generated from future experiments are made available to the (forensic) community, knowledge is needed on the key factors that underlie potential interlaboratory variation.The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientificdata. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation.
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| 3. |
- Kokshoorn, B., et al.
(författare)
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DNActivity: International cooperation in activity level interpretation of forensic DNA evidence : .
- 2015
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Ingår i: Abstracts ISFG. ; , s. 148-
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Konferensbidrag (refereegranskat)abstract
- Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activity level (i.e. ‘how did the DNA get there?’).To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects.Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientific data. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation. This project is funded by the European Union TVEFS-2020 program.
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| 4. |
- Seufferlein, T, et al.
(författare)
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[S3-guideline exocrine pancreatic cancer]
- 2013
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Ingår i: Zeitschrift fur Gastroenterologie. - : Georg Thieme Verlag KG. - 1439-7803 .- 0044-2771. ; 51:12, s. 1395-1440
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Tidskriftsartikel (refereegranskat)
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