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| 2. |
- von Beek, Christopher, et al.
(author)
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A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.
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| 3. |
- Akopyan, Karen, et al.
(author)
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Translocation of surface-localized effectors in type III secretion
- 2011
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:4, s. 1639-1644
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Journal article (peer-reviewed)abstract
- Pathogenic Yersinia species suppress the host immune response by using a plasmid-encoded type III secretion system (T3SS) to translocate virulence proteins into the cytosol of the target cells. T3SS-dependent protein translocation is believed to occur in one step from the bacterial cytosol to the target-cell cytoplasm through a conduit created by the T3SS upon target cell contact. Here, we report that T3SS substrates on the surface of Yersinia pseudotuberculosis are translocated into target cells. Upon host cell contact, purified YopH coated on Y. pseudotuberculosis was specifically and rapidly translocated across the target-cell membrane, which led to a physiological response in the infected cell. In addition, translocation of externally added YopH required a functional T3SS and a specific translocation domain in the effector protein. Efficient, T3SS-dependent translocation of purified YopH added in vitro was also observed when using coated Salmonella typhimurium strains, which implies that T3SS-mediated translocation of extracellular effector proteins is conserved among T3SS-dependent pathogens. Our results demonstrate that polarized T3SS-dependent translocation of proteins can be achieved through an intermediate extracellular step that can be reconstituted in vitro. These results indicate that translocation can occur by a different mechanism from the assumed single-step conduit model.
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| 4. |
- Antti, Henrik, et al.
(author)
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Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Journal article (peer-reviewed)abstract
- Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.
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| 5. |
- Avican, Kemal, et al.
(author)
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Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis
- 2015
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:1
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Journal article (peer-reviewed)abstract
- We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.
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| 6. |
- Borg, Andreas, et al.
(author)
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Analysing mathematical programming schemes using different lenses
- 2023
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In: Nordisk matematikkdidaktikk, NOMAD. - : University of Gothenburg, Sweden. - 1104-2176. ; 28:3–4, s. 199-219
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Journal article (peer-reviewed)abstract
- The use of programming in mathematics education is undergoing a renaissanceand, in this paper, we analyse students’ handling of programming in mathematicsusing the Instrumental approach as a theoretical lens. We are especially interestedin analysing the development of mental schemes using two analytical frameworkswhich are compared and contrasted according the idea of networking theories. Thestudy illustrates that the frameworks’ detail of richness can have both advantagesand disadvantages and that one of the frameworks are more customed to be appliedwhen analysing students’ instrumental genesis concerning the use of a programmingenvironment as a mathematical artefact.
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| 7. |
- Borg, Andreas
(author)
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Designing for the incorporation of programming in mathematical education : Programming as an instrument for mathematical problem solving
- 2021
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Licentiate thesis (other academic/artistic)abstract
- This study explored Swedish upper secondary school students’ use of programming for mathematical purposes. The aim of the study was to investigate the process through which students learn how to use a programming environment as a technical artefact during mathematical problem solving and how the orchestration of such learning situations could facilitate this process. In order to study the students’ use of the programming environment, design-based research was used as the main methodological approach. The design involved the development of specific mathematical tasks to be tried out with students, as well as the orchestration of the learning situation within the classroom e.g., by preparing scaffolding to be offered to the students. The subsequent implementation of the design was analysed so that, in accordance with the cyclic approach of design-based research, it could be revised ahead of the following design cycle. The study involved two complete design cycles. In the study, the Instrumental Approach was used as the theoretical framework and the instrumental genesis of the students in using a programming environment for mathematical purposes was thus of special interest. In order to analyse this process and the associated mental schemes developed by the students, Vergnaud’s concept of scheme served as an analytical framework. The findings revealed how the students, despite having basic knowledge in programming, experienced several difficulties when trying to use the programming environment as a technical mathematical artefact. These difficulties were related both to the fact that the mathematical affordances offered by the programming environment were unclear to many of the students, as well as to the handling of more specific computational concepts such as nested loops. The findings also revealed that the transformation of mathematical notations and ideas into programming code caused students difficulties.
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| 8. |
- Borg, Andreas, et al.
(author)
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Programming as a mathematical instrument : the implementation of an analytic framework
- 2020
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In: Mathematics Education in the Digital Age (MEDA) PROCEEDINGS. - 9783950463057 ; , s. 435-442
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Conference paper (peer-reviewed)abstract
- This paper relates to an ongoing project using design-based research as a methodol- ogical approach in which students with no prior experiences of using programming as a mathematical tool are observed trying to solve mathematical problems with the help of programming. The Instrumental Approach is used as conceptual framework in which the concept of instrumental genesis describes the process where the programming environment as an artefact together with student-developed mental schemes forms an instrument in order to solve mathematical problems. The development of schemes is of special interest in this paper where Vergnaud’s components of a scheme provide a framework for analysing transcripts of talk between student pairs and the programming code that they generate.
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| 9. |
- Brunström, Mats, 1960-, et al.
(author)
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Computer-aided assessment based on dynamic mathematics investigations
- 2020
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In: Proceedings of the Tenth ERME Topic Conference (ETC 10) on Mathematics Education in the Digital Age (MEDA), 16-18 September 2020 in Linz, Austria. - Linz, Austria.
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Conference paper (peer-reviewed)abstract
- In the poster, we will present a planned study focusing on the design of DMS tasks and elaborated feedback within a CAA system. The study will be conducted in a first year engineering mathematics course during autumn 2020.
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| 10. |
- Brunström, Mats, 1960-, et al.
(author)
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Designing for a combined use of a dynamic mathematics software environment and a computer-aided assessment system
- 2022
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In: Proceedings of the Twelfth Congress of the European Research Society in Mathematics Education (CERME12). - : ERME.
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Conference paper (peer-reviewed)abstract
- This paper reports on a pilot study with the focus on (re)design of a digitized task environment utilizing two types of technology – a dynamic mathematics software and a computer-aided assessment system. The data consist of responses from 256 first year engineering students, taking their first Calculus course, on two different types of task. The results are discussed in relation to (re)design of tasks as well as possible feedback design options to enable a formative assessment approach.
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