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| 2. |
- Dwibedi, Chinmay Kumar, et al.
(författare)
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Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis
- 2020
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample. We used parallel serial passage experiments and high-throughput sequencing of F. tularensis to explore the genetic variation. We found that during early laboratory culture passages of F. tularensis, gene duplications emerged in the pathogen genome followed by single-nucleotide polymorphisms in genes for bacterial capsule synthesis. Based on a biological enrichment scheme and the use of high-throughput sequencing, we identified genetic variation that likely pre-existed in a source sample. The results support that capsule synthesis gene mutations are common during laboratory culture, and that a biological amplification strategy is useful for linking a F. tularensis sample to a specific laboratory variant among many highly similar variants.
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| 3. |
- Elbir, Haitham, et al.
(författare)
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Genome Sequence of the Asiatic Species Borrelia persica
- 2014
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Ingår i: Genome Announcements. - 2169-8287. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the complete genome sequence of Borrelia persica, the causative agent of tick-borne relapsing fever borreliosis on the Asian continent. Its genome of 1,784,979 bp contains 1,850 open reading frames, three ribosomal RNAs, and 32 tRNAs. One clustered regularly interspaced short palindromic repeat (CRISPR) was detected.
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| 4. |
- Larsson, Pär, et al.
(författare)
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The complete genome sequence of Francisella tularensis, the causative agent of tularemia
- 2005
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 37:2, s. 153-159
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.
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| 5. |
- Larsson, Stefan, et al.
(författare)
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Characteristics of anadromous whitefish (Coregonus lavaretus (L.)) rivers in the Gulf of Bothnia
- 2013
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Ingår i: BIOLOGY AND MANAGEMENT OF COREGONID FISHES - 2011. - 9783510470662 ; 64, s. 189-201
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Konferensbidrag (refereegranskat)abstract
- In order to study anadromous whitefish spawning river requirements, we sampled 41 rivers in the Gulf of Bothnia for newly hatched whitefish larvae for one to three consecutive years. Chemical and morphological data (e.g. flow rate, topography, pH, estuary fetch and distance to coastal sandy areas) were collected for each river. Newly-hatched whitefish were caught in 19 rivers whereas whitefish were not confirmed present in 22 rivers. By applying partial least squares discriminant analysis (PLS-DA), data for rivers confirmed to support whitefish were contrasted with data for rivers in which whitefish were not found. The single most important factor was annual average water flow rate. Whitefish larvae were observed in 93% of the rivers with annual mean flow rate > 5 m(3) s(-1) (N = 14). In contrast, newly-hatched whitefish were only found in 22% of the smaller rivers (N = 27).
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| 6. |
- Larsson, Tobias, et al.
(författare)
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Project: PIEp - Product Innovation Engineering Programme
- 2011
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Annan publikation (populärvet., debatt m.m.)abstract
- PROJEKTSAMMANFATTNINGPIEp, Product Innovation Engineering Program är ett nationellt program som syftar till att stärka förmågan till innovativ produkt- och affärsutveckling. PIEp spänner över fältet från teori till praktik, från forskning om innovationssystem till proaktivt arbete för att stärka innovationskraft och därigenom uppnå en systemförändring inom forskning, utbildning och utveckling. PIEp skall pågå under tio år, 2007-2016 och engagera flera av Sveriges lärosäten och forskningsinstitut involverade i innovation och produktutveckling. PIEp leds och administreras vid KTH i partnerskap med Lunds Tekniska Högskola, Högskolan i Jönköping, Designhögskolan vid Umeå Universitet, Centrum för Teknik, Medicin och Hälsa, Luleå Tekniska Universitet, samt en rad företag och organisationer.
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| 7. |
- Larsson, Tobias, et al.
(författare)
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Project: ProViking THINK - Team för Heterogen Innovationskunskap
- 2008
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Annan publikation (populärvet., debatt m.m.)abstract
- Begreppet product-service systems (PSS), eller funktionella produkter, förutspås ha betydande påverkan för ett framtida hållbart samhälle. Ett PSS-synsätt kommer att förändra hur produkter och tjänster används, men också förändra tillvägagångssättet i utvecklingen, eftersom ansvaret för den fysiska produkten genom hela dess livscykel kvarstår hos företaget eller konsortiet som utvecklar PSS-lösningen. I och med detta kan aktiviteterna med omkonstruktion, återanvändning och återvinning, utföras på ett totalt annorlunda sätt än i dag. I den här situationen blir kapaciteten att ständigt förbättra kundupplevt värde genom nya lösningar en viktig förmåga. Således står utvecklingsteam idag inför två stora utmaningar; dels ska de kunna hantera mer abstrakta kundbehov, dels ska de på ett effektivt sätt ständigt bidra till nya lösningar. Det här projektets mål är att stödja PSS-utvecklingsteamets innovationsprocess genom att föreslå faciliterande metoder och verktyg. Specifikt fokus ligger på följande aspekter för att bidra till utvecklingen av en sammanhängande metodologi för team-baserad innovation:- Identifiering, analys och kommunikation av kundbehov samt modellering av värde- Tvärfunktionella team- Effektiv kunskapsdelning- Modellering och visualisering av lösningar baserat på ett kunskapslivscykel perspektiv Projektet kommer att vara en gemensam prestation av industri- och akademirepresentanter. Det praktiska arbetet kommer att utföras i ett nära samarbete. I stort vägleds projektet av antagandet att – visualisering av affärs- och utvecklingsrelaterad kunskap samt snabba modellerings- och simuleringsmöjligheter i tidiga faser stödjer PSS-teamets förmåga att finna nya lösningar och genomföra hållbar utveckling. Förutom ökad kunskap om strategier och tillvägagångssätt för team-baserad innovation kommer demonstratorer av verktyg och metoder vara ett resultat av projektarbetet.
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| 9. |
- Aaltonen, Kristina E., et al.
(författare)
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Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:28, s. 45544-45565
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to systemic therapy is a major problem in metastatic breast cancer (MBC) that can be explained by initial tumor heterogeneity as well as by evolutionary changes during therapy and tumor progression. Circulating tumor cells (CTCs) detected in a liquid biopsy can be sampled and characterized repeatedly during therapy in order to monitor treatment response and disease progression. Our aim was to investigate how CTC derived gene expression of treatment predictive markers (ESR1/HER2) and other cancer associated markers changed in patient blood samples during six months of first-line systemic treatment for MBC. CTCs from 36 patients were enriched using CellSearch (Janssen Diagnostics) and AdnaTest (QIAGEN) before gene expression analysis was performed with a customized gene panel (TATAA Biocenter). Our results show that antibodies against HER2 and EGFR were valuable to isolate CTCs unidentified by CellSearch and possibly lacking EpCAM expression. Evaluation of patients with clinically different breast cancer subgroups demonstrated that gene expression of treatment predictive markers changed over time. This change was especially prominent for HER2 expression. In conclusion, we found that changed gene expression during first-line systemic therapy for MBC could be a possible explanation for treatment resistance. Characterization of CTCs at several time-points during therapy could be informative for treatment selection.
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