| 1. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 2. |
- Cansby, Emmelie, 1984, et al.
(författare)
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Targeted Delivery of Stk25 Antisense Oligonucleotides to Hepatocytes Protects Mice Against Nonalcoholic Fatty Liver Disease
- 2019
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Ingår i: CMGH Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 7:3, s. 597-618
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide. Currently, no specific pharmacologic therapy is available for NAFLD/NASH, which has been recognized as one of the major unmet medical needs of the 21st century. Our recent studies in genetic mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine protein kinase (STK)25 as a critical regulator of hepatic lipid partitioning and NAFLD/NASH. Here, we studied the metabolic benefit of liver-specific STK25 inhibitors on NAFLD development and progression in a mouse model of diet-induced obesity. Methods: We developed a hepatocyte-specific triantennary N-acetylgalactosamine (GalNAc)-conjugated antisense oligonucleotide (ASO) targeting Stk25 and evaluated its effect on NAFLD features in mice after chronic exposure to dietary lipids. Results: We found that systemic administration of hepatocyte-targeting GalNAc-Stk25 ASO in obese mice effectively ameliorated steatosis, inflammatory infiltration, hepatic stellate cell activation, nutritional fibrosis, and hepatocellular damage in the liver compared with mice treated with GalNAc-conjugated nontargeting ASO, without any systemic toxicity or local tolerability concerns. We also observed protection against high-fat-diet–induced hepatic oxidative stress and improved mitochondrial function with Stk25 ASO treatment in mice. Moreover, GalNAc-Stk25 ASO suppressed lipogenic gene expression and acetyl-CoA carboxylase protein abundance in the liver, providing insight into the molecular mechanisms underlying repression of hepatic steatosis. Conclusions: This study provides in vivo nonclinical proof-of-principle for the metabolic benefit of liver-specific inhibition of STK25 in the context of obesity and warrants future investigations to address the therapeutic potential of GalNAc-Stk25 ASO in the prevention and treatment of NAFLD.
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| 3. |
- Malm, Magdalena, 1983-, et al.
(författare)
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Evolution from adherent to suspension: systems biology of HEK293 cell line development
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.
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| 4. |
- Saghaleyni, Rasool, 1987, et al.
(författare)
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Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 39:11
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate cellular and metabolic characteristics associated with these limitations, we compare HEK293 clones producing either erythropoietin (EPO) (secretory) or GFP (non-secretory) protein at different rates. Transcriptomic and functional analyses indicate significantly higher metabolism and oxidative phosphorylation in EPO producers compared with parental and GFP cells. In addition, ribosomal genes exhibit specific expression patterns depending on the recombinant protein and the production rate. In a clone displaying a dramatically increased EPO secretion, we detect higher gene expression related to negative regulation of endoplasmic reticulum (ER) stress, including upregulation of ATF6B, which aids EPO production in a subset of clones by overexpression or small interfering RNA (siRNA) knockdown. Our results offer potential target pathways and genes for further development of the secretory power in mammalian cell factories.
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| 5. |
- Boström, Elisabeth Almer, 1983, et al.
(författare)
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Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis.
- 2011
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Ingår i: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:10, s. 2894-904
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Tidskriftsartikel (refereegranskat)abstract
- Human resistin has proinflammatory properties that activate NF-κB-dependent pathways, whereas its murine counterpart is associated with insulin resistance. The aim of this study was to examine potential cross-talk between resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid arthritis (RA).
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| 6. |
- Cansby, Emmelie, 1984, et al.
(författare)
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Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders the shift from a contractile to a synthetic phenotype. Together, we provide several lines of evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.
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| 7. |
- Fuentes Martinez, Ana
(författare)
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Teachers’ tactics when programming and mathematics converge
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Teachers’ everyday practices are embedded in school contexts in which their teaching autonomy is constrained by rules, moral obligations, physical settings,and official directives. When a curricular revision mandated that programming was to be a part of mathematics in upper secondary education, teachers’ conditions changed. How teachers adapted to the new curriculum and how they navigated the tensions and contradictions that they encountered is in this thesis analyzed in terms of teachers’ tactics and policy strategies. The overall goal of the investigation is to contribute to a critical understanding of how mathematics teachers integrate programming in their professional practice and how this integration aligns and diverges from the intentions behind the reform. The empirical material is drawn from nine individual interviews with mathematics teachers that were already proficient in programming. The teachers’ unit plans and other lesson materials featuring programming activities served as a trigger point to delve into further reflections upon their own professional practices. To complete the scene, the policy documents were also examined. These included the mathematics curriculum, as well as related official documents and a collection of institutionally sanctioned programming exercises and demonstrations.Two tactical approaches were made apparent when mathematics teachers began to integrate computer programming in their subject: Dual teaching and Interspersed programming. The teacher’s use of dual teaching practices or interspersed programming are tactics shaped by and in response to the conditions of the new curriculum and their own preferences and views on student learning. These two tactics disclose different ontological commitments in relation to the strategies dictated by the curriculum and reflect a cardinal distinction between planning mathematics activities with elements of programming and planning programming activities with elements of mathematics. Of relevance for teachers and curriculum designers is the understanding of (a) how the notion of programming and mathematics as separate subjects oversimplifies teachers’ actual integration practices, and (b) how the curricular choices made by policy can shape the teaching tactics adopted by educators.
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| 8. |
- Haj-Bolouri, Amir, et al.
(författare)
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Designing a Web-Based Education Platform for Swedish Civic Orientation
- 2014
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Ingår i: Proceedings of the 37th Information Systems Research Seminar in Scandinavia (IRIS 37), Ringsted, Denmark, 10-13 August.. - Ringsted. - 9788773498767 ; , s. 1-13
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Konferensbidrag (refereegranskat)abstract
- Newcomers in Sweden face a problem of learning the Swedish society with respect to laws, culture, democratic values, education system, labor market and aspects of taking the role as a parent. The municipality of Gothenburg and the county administrative board in Västra Götaland are appointed by the Swedish government to educate newcomers in civic orientation. This paper describes some problems in providing distance education for Swedish civic orientation in forms of advanced learning modules (ALM). Requirements for implications for design were gathered through several conducted workshops together with relevant stakeholders through a participatory design approach. We concluded that our design for implications can be processed for future research and used together with a system solution.
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| 9. |
- Haj-Bolouri, Amir, 1985-
(författare)
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Designing for Adaptable Learning
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research in this thesis emphasizes the endeavor of designing for adaptable learning. Designing for adaptable learning is understood as an overall response to designing for integration work. Designing for integration work is thus classified as a special case of designing for adaptable learning. Integration work in this research is understood as a professional practice that aims to improve and support the integration process of newly arrived immigrants (referred to as newcomers) in society. As professional practitioners of integration work, integration workers face daily challenges that are wicked by nature. In order to understand and problematize these challenges, the empirical work of this research was organized and performed within a case of digitalizing the civic orientation program in Sweden. The civic orientation program is a special case of integration work in Sweden, where integration workers organize and provide civic orientation to newcomers in Sweden. Different groups of newcomers are subsequently participating in a required 60 hours of civic orientation and are provided sessions through their native language. The integration workers are responsible for organizing and performing civic orientation through a dynamic process of dialogues, exercises, and more. Integration work as a practice, however, does not incorporate a standardized knowledge base, which provides integration workers a unified way of organizing and performing civic orientation. Instead, different counties and municipalities in Sweden organize and perform civic orientation in various ways. Furthermore, due to the extreme heterogeneity among newcomers as participants in civic orientation, the integration workers are forced to adapt. In turn, the integration workers themselves are heterogeneous due to their different roles, areas of responsibilities, and more essentially, worldviews. In order to understand and problematize the aspects of designing for integration work, an explorative approach was adopted through three consecutive cycles of Action Design Research. The cycles were performed from 2013 until completion of this thesis. The thesis was subsequently governed through three research questions: (1) How to design for integration work? (2)What makes designing for integration work significant? (3) Why do design for integration work? There search questions were addressed and answered through a body of produced knowledge that captures and provides the essential contributions of the thesis. The contributions of the thesis highlight different aspects of designing for integration work, as a special case of designing for adaptable learning. Thus, the contributions are presented and discussed with an explicit bearing toward designing for adaptable learning,as the general class of problems and solutions of this research. The contributions are consequently provided through: (1) an ensemble artifact that is termed a digital platform for civic orientation; (2) an Information Systems Design Theory for adaptable e-learning; (3) a design research methodology that incorporates work-integrated learning; (4) the meta-design of an open learning platform that supports the social integration of newcomers in society; and (5) a philosophical concept that problematizes and conceptualizes the essence of presence in e-learning. Ultimately, the research contributes to the research domains of information systems and work-integrated learning, by providing findings that problematize core aspects of designing for adaptable learning. Furthermore, the thesis extensively discusses the findings of this research by emphasizing a philosophical perspective toward core aspects of the research contributions. Finally, the thesis concludes with a set of limitations of the current research and a brief discussion about potential endeavours of future research.
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| 10. |
- Haj-Bolouri, Amir, 1985-, et al.
(författare)
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Meta-requirements for Immersive Collaborative Spaces in Industrial Workplace Learning : Towards a Design Theory
- 2020
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Ingår i: Lecture Notes in Computer Science. - Cham : Springer Science and Business Media Deutschland GmbH. - 0302-9743 .- 1611-3349. ; 12388 LNCS, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- As the digital transformation of society accelerates, sophisticated Information Technologies (IT) emerge and are introduced into organizations and institutions of society. An example of such technologies is the Virtual Reality (VR) technology that has re-emerged and become a frequently used solution for supporting collaboration and workplace learning in immersive spaces. The deep sense of immersion in VR enables users to learn and develop working skills in an authentic virtual space, which facilitates an increased feeling of user presence and mapping with real world working scenarios. However, due to the emerging nature of using VR for collaboration and workplace learning, there are wide possibilities for Information Systems (IS) scholars to explore the prescriptive knowledge space of how to design and theorize VR technologies through Design Science Research (DSR). In this research in progress paper, we scrutinize the question of how to design immersive collaborative spaces for industrial workplace learning, and subsequently perform a preliminary round of literature review to address the question. Consequently, the findings of the review are reported as three meta-requirements, which we target as the contribution and input for further development of an information systems design theory. © 2020, Springer Nature Switzerland AG.
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