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- Borg, Jörgen, et al.
(author)
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Amino-terminal anchored surface display in insect cells and budded baculovirus using the amino-terminal end of neuraminidase.
- 2004
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In: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 114:1-2, s. 21-30
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Journal article (peer-reviewed)abstract
- Methods currently used for surface display on insect cells and budded baculovirus, all utilize the sequences from class I transmembrane proteins. This gives rise to some problems when handling unknown genes or cDNAs encoding full-length proteins. First, the stop codon from the cloned gene will be located upstream of the sequence for the transmembrane region. Second, the chance of getting the sequences encoding the signal peptide and the transmembrane region in frame with the cloned gene is small. To minimize these problems, we here present a method by which cDNAs or genes of interest can be cloned and fused to the codons for the signal peptide and transmembrane region of neuraminidase (NA), a class II transmembrane protein of the influenza virus. By placing both the signal peptide and transmembrane region at the amino-terminal, potential problems regarding stop codons are eliminated and errors in frame-shift minimized. To obtain proof of principle, the gene encoding enhanced green fluorescent protein, EGFP, was subcloned into a shuttle vector downstream of the neuraminidase sequence and the fusion product was then transferred to a baculovirus vector and transfected into insect cells (Sf9). Using this method, EGFP was found to be expressed on the surface of both infected cells and budded virus in an accessible manner.
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- Emami, S. Noushin, et al.
(author)
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A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection
- 2017
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6329
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Journal article (peer-reviewed)abstract
- Malaria infection renders humans more attractive to Anopheles gambiae sensu lato mosquitoes than uninfected people. The mechanisms remain unknown. We found that an isoprenoid precursor produced by Plasmodium falciparum, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), affects A. gambiae s. l. blood meal seeking and feeding behaviors as well as susceptibility to infection. HMBPP acts indirectly by triggering human red blood cells to increase the release of CO2, aldehydes, and monoterpenes, which together enhance vector attraction and stimulate vector feeding. When offered in a blood meal, HMBPP modulates neural, antimalarial, and oogenic gene transcription without affecting mosquito survival or fecundity; in a P. falciparum-infected blood meal, sporogony is increased.
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- Hedberg, Yolanda
(author)
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Environmental and health aspects of corrosion– importance of chemical speciation
- 2010
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Licentiate thesis (other academic/artistic)abstract
- During the last decades, the interest in corrosion of metals and alloys from an environmental and health perspective has increased rapidly as a consequence of stricter environmental and human exposure legislations, their extensive use as implant materials and an increasing understanding related to occupational and/or daily exposure to airborne particles. Corrosion-induced metal release, however, needs to be understood in detail and to include knowledge related to chemical speciation, i.e. the oxidation state, complexation and chemical form of released metals, parameters of high importance when considering toxicity. In this licentiate work, corrosion-induced metal runoff from roofing materials (copper, zinc, and chromium(III)-, and chromium(VI) surface treated galvanized steel) has been investigated from an environmental perspective with focus on chemical speciation of released metals (Papers I-II). From these papers it was evident that the total concentration measured in the runoff water is not sufficient for any environmental risk assessment. The environmental fate including changes in chemical speciation and hence metal precipitation has to be considered. For example, it was shown that the copper concentration decreased by three orders of magnitude already in the internal drainage system of a shopping centre with a copper roof, to a concentration lower than storm water collected from a nearby parking space (Paper I). Also, speciation measurements can explain corrosion, metal release and surface processes of chromium surface treated galvanized steel at different sites (urban and marine). Any environmental risk assessment has to be done by considering all metal species released, and compared with ecotoxic values. For example, when most chromium(VI) (the most toxic species) was released, significantly less zinc was released at the same time which decreased the overall ecotoxicity of the runoff water significantly (Paper II). When assessing environmental risks by standard laboratory tests, it is important to understand all mechanisms which are possibly influenced by individual experimental parameters and which often are different for different test substances. Some metals released, as seen in the case of iron, may precipitate with time and be pH-, solution- and buffering dependent. This behavior can lead to strongly underestimated measured metal concentrations (Paper III). When particles of metals or alloys are to be investigated (Papers III-VI), it is essential to conduct a thorough particle characterization, since the surface properties cannot be defined. In addition, the surface properties (oxide layer properties) change with varying particle size (Paper VI) and with other experimental parameters such as dispersion (Paper VI). All iron-, and chromium-based particles investigated (Papers III-VI) revealed large differences between alloy particles and pure metals. Particles of pure iron and nickel released significantly more metals compared with particles of the investigated alloys, whereas particles of pure chromium released less metals compared with the alloys. Particles of stainless steel (AISI 316L), ferro-chromium and ferro-silicon-chromium released very low amounts of metals (Papers III-VI). The released quantity increased with increased acidity (Papers III-VI) and also in the presence of complexing agents (ongoing research). The manufacturing process is of high importance, as observed for stainless steel particles when compared with a side product from stainless steel production with similar composition that released significantly more metals (Paper III). Particles of metal oxides, i.e. chromium(III)oxide and iron(II,III)oxide, released very low amounts of metals due to their thermodynamic stability. Ongoing research activities focus on the specific influence of complexing agents and proteins on the metal release process from massive sheet and particles of metals and alloys. The applicability and the possibility to use different analytical tools are investigated and elaborated for small-sized particles. A detailed understanding of the correlation between material and particle characteristics, the metal release process, the chemical speciation in interaction with proteins and/or cells, and the particle/cell interaction is essential to enable any correlation between material/particle characteristics and toxicity. The aim of this licentiate summary is – in contrast to the six included scientific papers – to explain the importance of chemical speciation for corrosion processes from a health and environmental perspective in a popular way to reach a broad non-academic audience. The summary is hence written as a guidance document for stakeholders and the regulatory community working with environmental and health risk assessment.
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| 7. |
- Li, Constance H., et al.
(author)
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Sex differences in oncogenic mutational processes
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Journal article (peer-reviewed)abstract
- Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
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| 8. |
- Nik-Zainal, Serena, et al.
(author)
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Mutational Processes Molding the Genomes of 21 Breast Cancers
- 2012
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5, s. 979-993
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Journal article (peer-reviewed)abstract
- All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
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| 9. |
- Nik-Zainal, Serena, et al.
(author)
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The Life History of 21 Breast Cancers
- 2012
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5
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Journal article (peer-reviewed)abstract
- Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
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| 10. |
- Nordin, Susanna, et al.
(author)
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Digital homecare twin expectations among Swedish social service professionals – a qualitative study
- 2024
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Conference paper (peer-reviewed)abstract
- Digital homecare twin expectations among Swedish social service professionals – a qualitative studyBackground and purposeDesigning care and support interventions that are tailored to the persons’ needs is essential to high-quality care and is increasingly recognised as associated with positive effects on the health and well-being of older adults and caregivers. In line with demographic trends observed in many countries, Sweden is confronted with a double demographic challenge where the proportion of older adults is increasing while the proportion of people of working age is decreasing. This will lead to a significant shortage of personnel within the sector of health and social care services by the year 2030 with the risk of deteriorations in the quality of care. This pressing situation underscores an urgent need for novel and innovative solutions in municipal homecare. Therefore, the purpose of this study was to identify expectations of social service professionals in Sweden concerning a digital homecare twin intended to support person-centeredness and enhance the working environment in homecare. A digital twin serves as a digital representation of assets, processes, and systems, which in the context of homecare includes older adults and their homes, as well as homecare services and personnel. This study constitutes an integral part of a broader research project aimed at the co-development and evaluation of a digital twin for homecare, which is based on Industry 4.0 technology. MethodsThe present study adopted a qualitative design with four focus groups involving thirty participants working in municipal homecare in urban and rural locations. They represented a diverse spectrum of social service roles: homecare workers, planners, IT specialists, and managers across various levels of responsibility. During the two-hour focus group sessions, the participants discussed three topics: valuable aspects of homecare; knowledge needs for effective homecare delivery; and anticipations related to a digital twin. The focus group sessions were recorded, transcribed verbatim and analysed thematically. FindingsThe analysis will be completed by the end of 2023 and the preliminary results will be presented at ECSWR 2024.Conclusions and implicationsThe present study can contribute to valuable knowledge on how a digital twin can be used in homecare, and the results are expected to support person-centered homecare and increase job satisfaction for homecare workers. The main outcomes and their implications for practice and further research will be presented at ECSWR 2024.
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