| 1. |
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| 2. |
- Amlinger, Lina, et al.
(författare)
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Fluorescent CRISPR Adaptation Reporter for rapid quantification of spacer acquisition
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- CRISPR-Cas systems are adaptive prokaryotic immune systems protecting against horizontally transferred DNA or RNA such as viruses and other mobile genetic elements. Memory of past invaders is stored as spacers in CRISPR loci in a process called adaptation. Here we developed a novel assay where spacer integration results in fluorescence, enabling detection of memory formation in single cells and quantification of as few as 0.05% cells with expanded CRISPR arrays in a bacterial population. Using this fluorescent CRISPR Adaptation Reporter (f-CAR), we quantified adaptation of the two CRISPR arrays of the type I-E CRISPR-Cas system in Escherichia coli, and confirmed that more integration events are targeted to CRISPR-II than to CRISPR-I. The f-CAR conveniently analyzes and compares many samples, allowing new insights into adaptation. For instance, we show that in an E. coli culture the majority of acquisition events occur in late exponential phase.
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| 3. |
- Bindal, Gargi, et al.
(författare)
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Type I-E CRISPR-Cas System as a Defense System in Saccharomyces cerevisiae
- 2022
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Ingår i: mSphere. - : American Society for Microbiology. - 2379-5042. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Defense against viruses and other mobile genetic elements (MGEs) is important in many organisms. The CRISPR-Cas systems found in bacteria and archaea constitute adaptive immune systems that can acquire the ability to target previously unrecognized MGEs. No CRISPR-Cas system is found to occur naturally in eukaryotic cells, but here, we demonstrate interference by a type I-E CRISPR-Cas system from Escherichia coli introduced in Saccharomyces cerevisiae. The designed CRISPR arrays are expressed and processed properly in S. cerevisiae. Targeted plasmids display reduced transformation efficiency, indicative of DNA cleavage. IMPORTANCE Genetic inactivation of viruses and other MGEs is an important tool with application in both research and therapy. Gene editing using, e.g., Cas9-based systems, can be used to inactivate MGEs in eukaryotes by introducing specific mutations. However, type I-E systems processively degrade the target which allows for inactivation without detailed knowledge of gene function. A reconstituted CRISPR-Cas system in S. cerevisiae can also function as a basic research platform for testing the role of various factors in the interference process. Genetic inactivation of viruses and other MGEs is an important tool with application in both research and therapy. Gene editing using, e.g., Cas9-based systems, can be used to inactivate MGEs in eukaryotes by introducing specific mutations.
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| 4. |
- Brouns, Stan J, et al.
(författare)
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Small CRISPR RNAs guide antiviral defense in prokaryotes
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 321:5891, s. 960-964
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Tidskriftsartikel (refereegranskat)abstract
- Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
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| 5. |
- Bärring, Maja, 1988, et al.
(författare)
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5G Enabled Manufacturing Evaluation for Data-Driven Decision-Making
- 2018
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 27, s. 266-271
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Konferensbidrag (refereegranskat)abstract
- Manufacturing industries are experiencing a technical paradigm shift that will change how they run their operations. Equipment and personnel generate an ever-increasing amount of data, and connectivity enables to utilize data to a larger extent. Connecting a machine is not a technical obstacle anymore, but with all available data, the challenge is to understand the requirements of data to support efficient decision-making. This paper will address the requirements of data by domain experts, in the context of more real-time data available. A focus group interview was performed, assessing the key factors of big data; volume, velocity, and variety of data.
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| 6. |
- Ettema, Thijs J. G., et al.
(författare)
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Rolf Bernander (1956-2014) : pioneer of the archaeal cell cycle Obituary
- 2014
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Ingår i: Molecular Microbiology. - : John Wiley & Sons. - 0950-382X .- 1365-2958. ; 92:5, s. 903-909
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- On 19 January 2014 Rolf (Roffe') Bernander passed away unexpectedly. Rolf was a dedicated scientist; his research aimed at unravelling the cell biology of the archaeal domain of life, especially cell cycle-related questions, but he also made important contributions in other areas of microbiology. Rolf had a professor position in the Molecular Evolution programme at Uppsala University, Sweden for about 8 years, and in January 2013 he became chair professor at the Department of Molecular Biosciences, The Wenner-Gren Institute at Stockholm University in Sweden. Rolf was an exceptional colleague and will be deeply missed by his family and friends, and the colleagues and co-workers that he leaves behind in the scientific community. He will be remembered for his endless enthusiasm for science, his analytical mind, and his quirky sense of humour.
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| 7. |
- Hammar, Henrik, 1970, et al.
(författare)
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The kilometer tax and Swedish industry-effects on sectors and regions
- 2011
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Ingår i: Applied Economics. - London : Chapman and Hall. - 0003-6846 .- 1466-4283. ; 43, s. 2907-2917
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Tidskriftsartikel (refereegranskat)abstract
- An introduction of a kilometer tax for heavy goods vehicles can be constrained by the risk of that higher production costs than competitors in other countries will negatively affect regions and industries of policy concern. We estimate factor demand elasticities in the Swedish manufacturing industry using firm level data for the 1990 to 2001 period on input prices and quantities. The results show that the introduction of a kilometer tax for heavy goods vehicles decreases transport demand and increases labour demand. The effects are less pronounced in terms of changes in output, though some industries (e.g. wood, pulp and paper) can be expected to be affected more than others due to their dependence on road freight transport. The regional dimension regarding the consequences of a kilometer tax seems to be small or even nonexisting.
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| 8. |
- Hoekzema, Mirthe
(författare)
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Small RNAs, Big Consequences : Post-transcriptional Regulation and Adaptive Immunity in Bacteria
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is nowadays widely accepted that non-coding RNAs play important roles in post-transcriptional regulation of genes in all kingdoms of life. In bacteria, the largest group of RNA regulators are the small RNAs (sRNAs). Almost all sRNAs act through anti-sense base-pairing with target mRNAs, and by doing so regulate their translation and/or stability. As important modulators of gene expression, sRNAs are involved in all aspects of bacterial physiology. My studies aimed to deepen our understanding of the mechanisms behind sRNA-mediated gene regulation. We have shown that translation of the di-guanylate-cyclase YdaM, a major player in the biofilm regulatory cascade, is repressed by the sRNAs OmrA and OmrB. OmrAB require the RNA chaperone protein Hfq for efficient regulation. Interestingly, our results suggest a non-canonical mechanism for Hfq-mediated ydaM-OmrA/B base-pairing. Instead of serving as RNA interaction platform, Hfq restructures the ydaM mRNA to enable sRNA binding. We also addressed the question of how bacteria utilize regulatory RNAs to create phenotypic heterogeneity by studying the role of the tisB/istR-1 type 1 toxin-antitoxin system in SOS-induced persister cell formation in E. coli.In addition, I have investigated the prokaryotic CRISPR-Cas immune system, which has led to the development of two molecular tools. The CRISPR-Cas adaptive immune system consists of a CRISPR array, where palindromic repeats are interspaced by unique spacer sequences derived from foreign genetic elements, and the CRISPR-associated (Cas) proteins. In the adaptation stage, memory is created by insertion of spacer sequences into the CRISPR array. We developed a fluorescent reporter that accurately and sensitively detects spacer integration events (denoted: “acquisition”) in single cells and in real-time. In the effector stage of immunity, crRNAs, consisting of one spacer-repeat unit, associate with the Cas proteins to form a ribonucleoprotein complex that surveys the cell for invader DNA. Target identification occurs by base-pairing between the crRNA and the complementary sequence in the target nucleic acid, which triggers degradation. We repurposed the E. coli type I-E CRISPR-Cas effector complex Cascade for specific reprogrammable transcriptional gene silencing.The studies presented herein thus contributes to our understanding of RNA-based target identification for gene regulation and adaptive immunity.
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| 9. |
- Jore, Matthijs, et al.
(författare)
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Structural basis for CRISPR RNA-guided DNA recognition by Cascade
- 2011
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 18:5, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.
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| 10. |
- Klamberg, Mark, 1975-
(författare)
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Norm development in the UN Security Council : Codebook
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This dataset contains information on language and speech-acts by the UN Security Council (UNSC) and its member states. More specifically, the focus lies on how the UNSC as a whole, in its resolutions, and the individual member states “talk” about the norms and issues that are construed as threats against international peace and security.
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| 11. |
- Krupenko, Darya, et al.
(författare)
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Polymorphic parasitic larvae cooperate to build swimming colonies luring hosts
- 2023
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Ingår i: Current Biology. - : Cell Press. - 0960-9822 .- 1879-0445. ; 33:20, s. 4524-4531
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Tidskriftsartikel (refereegranskat)abstract
- Parasites have evolved a variety of astonishing strategies to survive within their hosts, yet the most chal-lenging event in their personal chronicles is the passage from one host to another. It becomes even more complex when a parasite needs to pass through the external environment. Therefore, the free-living stages of parasites present a wide range of adaptations for transmission. Parasitic flatworms from the group Di-genea (flukes) have free-living larvae, cercariae, which are remarkably diverse in structure and behavior. One of the cercariae transmission strategies is to attain a prey-like appearance for the host. This can be done through the formation of a swimming aggregate of several cercariae adjoined together by their tails. Through the use of live observations and light, electron, and confocal microscopy, we described such a supposedly prey-mimetic colony comprising cercariae of two distinct morphotypes. They are functionally specialized: larger morphotype (sailors) enable motility, and smaller morphotype (passengers) presumably facilitate infection. The analysis of local read alignments between the two samples reveals that both cercaria types have identical 18S, 28S, and 5.8S rRNA genes. Further phylogenetic analysis of these ribo-somal sequences indicates that our specimen belongs to the digenean family Acanthocolpidae, likely genus Pleorchis. This discovery provides a unique example and a novel insight into how morphologically and functionally heterogeneous individuals of the same species cooperate to build colonial organisms for the purpose of infection. This strategy bears resemblance to the cooperating castes of the same species found among insects.
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| 12. |
- Lundgren, Magnus, 1975-
(författare)
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Archaeal Chromosome
- 2008
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Ingår i: Encyclopedia of Life Sciences. - Chichester, England : John Wiley & Sons. - 0470664789 - 9780470015902
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Bokkapitel (refereegranskat)abstract
- The Archaea is one of the three domains of life, and the least known. Sequencing ofmany archaeal chromosomes has shown that archaea display many eukaryotic features,despite sharing their appearance and range of genome size with bacteria. Chromatinorganization, replication and transcription are similar to eukaryotes while operonorganization and transcription regulation are similar to bacteria.
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| 13. |
- Lundgren, Magnus, 1975-
(författare)
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Exploring the Cell Cycle of Archaea
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Archaea is the third domain of life, discovered only thirty years ago. In a microscope archaea appear indistinguishable from bacteria, but they have been shown to be more closely related to eukaryotes than to bacteria. Especially central information processing is homologous to that of eukaryotes. The archaea, previously thought to be limited to extreme environments, constitute a large part of life on Earth to an extent that has only begun to be understood. Despite their abundance little is known about several central cell-cycle features, such as cell division and genome segregation.For this thesis, a comprehensive study of the cell cycle in the model archaeon Sulfolobus acidocaldarius was performed, describing the majority of its cell-cycle regulated genes. Several known DNA replication genes, as well as genes previously not known to have a role in the cell cycle, displayed cyclic transcription. Several transcription factors, kinases and DNA sequence elements were identified as cell-cycle regulatory elements. Among the most important findings were putative cell division and genome segregation machineries.Sulfolobus species were discovered to have three origins of replication, constituting the first known prokaryotes with multiple origins. All origins initiate replication in a synchronous manner. Cdc6 proteins were shown to bind to origin recognition boxes conserved across the Archaea domain. Two Cdc6 proteins function as replication initiators, while a third paralog is implicated as a negative factor. Replication was shown to proceed at a rate similar to that of eukaryotes.A particular type of cell cycle organization was found to be unusually conserved in the Crenachaeota phylum. All the studied species displayed a short prereplicative phase and a long postreplicative phase, and cycle between one and two genome copies. Genome sizes were determined for several species. The euryarchaeon Methanothermobacter thermautotrophicus was also studied, and it was shown to initiate genome segregation during, or just after, replication. In contrast to the crenarchaea it never displayed a single genome copy per cell.
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| 14. |
- Lundgren, Magnus, et al.
(författare)
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Selective Attention : The United Nations Security Council and Armed Conflict
- 2023
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Ingår i: British Journal of Political Science. - 0007-1234 .- 1469-2112. ; 53:3, s. 958-979
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Tidskriftsartikel (refereegranskat)abstract
- What explains why the United Nations Security Council meets and deliberates on some armed conflicts but not others? We advance a theoretical argument centred on the role of conflict externalities, state interests and interest heterogeneity. We investigate data on the Security Council's deliberation on armed conflicts in the 1989–2019 period and make three key findings: (1) conflicts that generate substantive military or civilian deaths are more likely to attract the Security Council's attention; (2) permanent members are varyingly likely to involve the Security Council when their interests are at stake; and (3) in contrast to the conventional wisdom, conflicts over which members have divergent interests are more likely to enter the agenda than other conflicts. The findings have important implications for debates about the Security Council's attention, responsiveness to problems and role in world politics.
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| 15. |
- Sengpiel, Verena, 1977, et al.
(författare)
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Confirmed reinfection with SARS-CoV-2 during a pregnancy: A case report.
- 2022
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Ingår i: Clinical case reports. - : Wiley. - 2050-0904. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy might impact immunity after SARS-CoV-2 infection and/or vaccination. We describe the first case of reinfection with SARS-CoV-2 during a pregnancy. While the mother lacked detectable antibodies 2months after the first infection, both mother and baby had IgG antibodies at delivery. Infection did not cause any adverse pregnancy outcome.
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| 16. |
- Tallberg, Jonas, 1971-, et al.
(författare)
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The Global Governance of Artificial Intelligence : Next Steps for Empirical and Normative Research
- 2023
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Ingår i: International Studies Review. - 1521-9488 .- 1468-2486. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) represents a technological upheaval with the potential to change human society. Because of its transformative potential, AI is increasingly becoming subject to regulatory initiatives at the global level. Yet, so far, scholarship in political science and international relations has focused more on AI applications than on the emerging architecture of global AI regulation. The purpose of this article is to outline an agenda for research into the global governance of AI. The article distinguishes between two broad perspectives: an empirical approach, aimed at mapping and explaining global AI governance; and a normative approach, aimed at developing and applying standards for appropriate global AI governance. The two approaches offer questions, concepts, and theories that are helpful in gaining an understanding of the emerging global governance of AI. Conversely, exploring AI as a regulatory issue offers a critical opportunity to refine existing general approaches to the study of global governance.
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| 17. |
- Weman-Josefsson, Karin Anna, 1975-
(författare)
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EXPLORING MOTIVATIONAL MECHANISMS IN EXERCISE BEHAVIOUR : Applying Self-determination theory in a person-centred approach
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Involvement in physical activity (PA) and exercise behaviour is multifaceted and depends on bidirectional correlations between multiple factors; one avenue to increase the understanding of sustainable exercise behaviours would be to employ a motivational perspective. In this thesis, this was done by placing the primary focus on Self-determination theory (SDT) as a person-centred approach to study the motivational mechanisms believed to impact exercise behaviour based on the SDT process model. Study 1, conducted in a cross-sectional design, included 1,091 members of a web-based exercise service. Based on sophisticated mediation analysis, the results support the hypothesized associations between latent constructs and exercise behaviour in the related steps of the SDT process model. Moreover, moderating effects were discovered, demonstrating that these associations could differ in different subgroups based on gender and age. The results of Study 1 thereby represent a first indication that exercise intervention design might benefit from slightly different approaches when addressing different demographical groups like gender and age. Study 2 was conducted in a two-wave RCT design to test an SDT-informed intervention on 64 voluntary participants. Components of Motivational interviewing (MI), the Relapse prevention model (RPM) and Cognitive behavioural therapy (CBT) were used as practical application guidelines to deliver the intervention content. Results showed intervention effects on exercise level, exercise intensity and motivation quality as well as mediating effects of the RAI (Relative Autonomy Index; an index of the degree of self-determination), and identified regulation in relation to exercise behaviour. The experimental group also demonstrated significantly lower levels of extrinsic motivation than the control group post-intervention. Besides strong support for applying the basic tenets of SDT in the exercise domain, there are some main findings in this thesis. First of all, self-determined motivation was found to act as a mediating variable in the relationship between psychological need satisfaction and exercise, and these patterns of indirect effects differed across age and gender. This indicates that mechanisms in the SDT process model could vary (qualitatively) depending on subgroup, which carries potential implications for practice. Second, the results of Study 2 also provide evidence that the mediating mechanisms of the process model could be manipulated in an intervention, e.g. by creating need-supportive environments facilitating internalization and subsequent exercise behaviour. Furthermore, both studies demonstrated that identified regulation plays a prominent role in the motivational processes, supporting the significance of promoting internalization in activities like exercise. Finally, this thesis represents prospective value for the utility of employing a polytheoretical approach in exercise intervention design, more specifically regarding the prosperous outlooks in combining SDT with other theories and methods.
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