| 1. |
- Ågerstrand, Marlene, et al.
(author)
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A call for action : Improve reporting of research studies to increase the scientific basis for regulatory decision-making
- 2018
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In: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 38:5, s. 783-785
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Journal article (peer-reviewed)abstract
- This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer-reviewed research studies in regulatory decision-making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.
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| 2. |
- Appelgren, Henrik, et al.
(author)
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Distinct centromere domain structures with separate functions demonstrated in live fission yeast cells
- 2003
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In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 116:19, s. 4035-4042
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Journal article (peer-reviewed)abstract
- Fission yeast (Saccharomyces pombe) centromere DNA is organized in a central core region flanked on either side by a region of outer repeat (otr) sequences. The otr region is known to be heterochromatic and bound by the Swi6 protein whereas the central core region contains an unusual chromatin structure involving the histone H3 variant Cnp1 (S. pombe CENP-A). The central core is the base for formation of the kinetochore structure whereas the flanking region is important for sister centromere cohesion. We have previously shown that the ultrastructural domain structure of S. pombe centromeres in interphase is similar to that of human centromeres. Here we demonstrate that S. pombe centromeres are organized in cytologically distinct domains even in mitosis. Fluorescence in situ hybridization of fixed metaphase cells revealed that the otr regions of the centromere were still held together by cohesion even after the sister kinetochores had separated. In live cells, the central cores and kinetochores of sister chromosomes could be distinguished from one Another when they were subjected to mitotic tension. The function of the different centromeric domains was addressed. Transacting mutations affecting the kinetochore (nuf2) central core domain (mis6) and the heterochromatin domain (rik1) were analyzed in live cells. In interphase, both nuf2 and mis6 caused declustering of centromeres from the spindle pole body whereas centromere clustering was normal in rik1 despite an apparent decondensation defect. The declustering of centromeres in mis6 cells correlated with loss the Ndc80 kinetochore marker protein from the centromeres. Interestingly the declustered centromeres were still restricted to the nuclear periphery thus revealing a kinetochore-independent peripheral localization mechanism for heterochromatin. Time-lapse microscopy of live mis6 and nuf2-1 mutant cells in mitosis showed similar severe misaggregation phenotypes whereas the rik1 mutants showed a mild cohesion defect. Thus, S. pombe centromeres have two distinguishable domains even during mitosis, and our functional analyses support the previous observations that the kinetochore/central core and the heterochromatin domains have distinct functions both in interphase and mitosis.
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| 3. |
- Appelgren, Henrik, 1965-
(author)
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Spontaneous and induced mutations at the human minisatellite MS32 in yeast
- 1999
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Doctoral thesis (other academic/artistic)abstract
- Tandem repetitive DNA including minisatellites make up a large part of eukaryotic genomes, and some tandem repetitive loci are associated with human disease. Little is known about the functions and dynamics of these sequences. Hypervariable minisatellites are used as naturally occurring genetic markers and form the basis of DNA fingerprinting. Studies in human have shown that minisatellite alleles frequently mutate to new lengths by recombination-based mechanisms that operate in the germline, possibly in meiosis. In addition to the variability in length, all hypervariable minisatellites characterised to date also show variation in the DNA sequence of repeat units. The order of variant repeat units can be revealed by MVR-PCR (Minisatellite Variant Repeat mapping by PCR), and this has greatly contributed to mutation analysis by comparing structures of alleles before and after mutation. Certain aspects of minisatellite mutation and general eukaryotic meiotic recombination, cannot be studies in human or any other mammalian system. It was therefore necessary to develop a manipulable eukaryotic model system in the yeast Saccharomyces cerevisiae. The best characterised human minisatellite MS32 was integrated in the vicinity of a hotspot for meiotic recombination in chromosome III. This thesis presents the construction of the model system and analyses of MS32 mutation in yeast.The results proved that MS32 mutation is induced in meiosis. Mutant structures were strikingly similar to mutant structures seen in man. Tetrad analysis demonstrated that gene conversion is the major pathway leading to interallelic exchanges. The data also suggested that a hyper-recombinogenic state is formed, and it was shown that entire alleles can be transferred from a chromatid to another. An allele that displays reduced mutation rate in man showed a reduced mutation rate also in yeast. The results have implications for general eukaryotic meiotic recombination. Mutations at MS32 were induced in meiosis by PCB, suggesting that the model system can be used as an in vitro bioassay for the screening of environmental contaminants capable of inducing genomic damage in meiosis. It is concluded that the yeast model constitute a suitable system for the molecular dissection of pathways in spontaneous and induced minisatellite mutations and for elucidating general eukaryotic meiotic recombination mechanisms.
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| 4. |
- Appelgren Heyman, Frej, et al.
(author)
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Can we rely on text originality check systems? : Evaluation of three systems used in higher education and suggestion of a new methodological test approach
- 2012
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In: 5th International Plagiarism Conference Proceedings & Abstracts 2012. - Newcastle GB : Iparadigms Europe Ltd. - 9780957311503
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Conference paper (peer-reviewed)abstract
- This study investigates the reliability of three originality check systems from the university teacher's perspective. It also describes a method for evaluating this type of systems. The three systems are examined with respect to the time used for the search, the ability to find plagiarism and the layout of the similarity report. The study was conducted in conjunction with the national procurement of a new national agreement for originality check systems and a Swedish higher education institution choice of a new system. The background is the teachers' use of the originality check system as part of the pedagogical efforts to prevent plagiarism and detect suspected fraud. The study does not discuss the whole plagiarism issue in higher education. Instead it focuses on the method used for the evaluation of and comparison between systems. Over 68,000 words from 167 plagiarized references, from different sources and subject areas were used to test the systems. The results show that systems can find only a portion of the plagiarized texts that were sent in to the systems for control and that there are major differences between the capabilities of the systems. 20, 63 and respectively 84 of the 167 references were indicated as plagiarism. Turnitin conducted searches of up to five minutes while the other two systems sometimes took considerably more time for the analysis. The investigation of the originality reports´ interface revealed that factors the evaluators considered differed between these systems. This disclosed that the reports can be more or less difficult to interpret. We can therefore not solely rely on the originality check system´s reliability. Consequently this leads to the conclusion that other educational activities should be emphasized as a much needed complement in the work of preventing and detecting fraud in the form of plagiarism
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| 5. |
- Facanha, A L O, et al.
(author)
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The endoplasmic reticulum cation P-type ATPase Cta4p is required for control of cell shape and microtubule dynamics
- 2002
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In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 157:6, s. 1029-1039
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Journal article (peer-reviewed)abstract
- Here we describe the phenotypic characterization of the cta(4+) gene, encoding a novel member of the P4 family of P-type ATPases of fission yeast. The cta4Delta mutant is temperature sensitive and cold sensitive lethal and displays several morphological defects in cell polarity and cytokinesis. Microtubules are generally destabilized in cells lacking Cta4p. The microtubule length is decreased, and the number of microtubules per cell is increased. This is concomitant with an increase in the number of microtubule catastrophe events in the midzone of the cell. These defects are likely due to a general imbalance in cation homeostasis. Immunofluorescence microscopy and membrane fractionation experiments revealed that green fluorescent protein-tagged Cta4 localizes to the ER. Fluorescence resonance energy transfer experiments in living cells using the yellow cameleon indicator for Ca2+ indicated that Cta4p regulates the cellular Ca2+ concentration. Thus, our results reveal a link between cation homeostasis and the control of cell shape, microtubule dynamics, and cytokinesis, and appoint Ca2+ as a key ion in controlling these processes.
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| 6. |
- Robinson, Yohan, 1977, et al.
(author)
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AI och framtidens försvarsmedicin
- 2020
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Reports (other academic/artistic)abstract
- Medicinskt legitimerad personal är, och kommer med stor sannolikhet fortsattatt vara, en knapp resurs inom Försvarsmaktens sjukvårdsorganisation. I denna rapport ges en översikt över pågående och planerade ansatser baserade påartificiell intelligens (AI) inom akutsjukvård med särskild tonvikt på omhändertagandet av traumapatienter, där lösningarna skulle kunna bidra till att Försvarsmakten kan bibehålla sin sjukvårdskapacitet i kritiska lägen. Rapporten är ett resultat av samarbetet mellan FM, FOI, FMV, FHS och KI, och vänder sig i första hand till Försvarsmaktens strategiska ledning.Användningen av AI-teknik i framtida beslutsstöd kan skapa nya möjligheter till avlastning av personal och resurseffektivisering. Tekniken ger möjligheter att i realtid samla in, bearbeta och analysera stora mängder blandadinformation om förbands hälsoläge och fysiska stridsvärde. Bedömning av skadade kan t.ex. göras av triagedrönare och den efterföljande evakueringen kanunderlättas av intelligenta autonoma plattformar. Införandet av AI-system ställer dock vårdgivaren inför svåra etiska och medikolegala överväganden.Försvarsmedicin har en central roll i Försvarsmaktens krigföringsförmåga och för samhällets uthållighet. För att nyttja hela AI-teknikens framfart till Försvarsmaktens nytta måste dess innebörd och konsekvens för försvarsmedicinen förstås. Därför rekommenderar denna studie att Försvarsmaktens framtida satsningar inom AI och autonomi inkluderar den försvarsmedicinska teknikutveckling som är beskriven i denna rapport.
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