| 1. |
- Andersson, Linus, 1979-, et al.
(author)
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Chemical Intolerance Is Associated With Altered Response Bias, not Greater Sensory Sensitivity
- 2020
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In: i-Perception. - : Sage Publications. - 2041-6695. ; 11:6
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Journal article (peer-reviewed)abstract
- Chemical intolerance is a surprisingly prevalent condition or affliction characterized by adverse reactions to low levels of chemical, often odorous stimulation. Sufferers often assume that their plight is due to an uncommon sensory acuteness, yet studies repeatedly fail to reveal altered detection thresholds. Here, we investigated whether self-reported chemical intolerance is associated with altered sensory sensitivity or response bias. The sensory acuity (sensitivity; A) and sensory decision rule (criterion; B) to n-butanol was assessed using the method of constant stimuli in 82 participants with different degrees of chemical intolerance (low to high). Higher self-reported chemical intolerance was associated with a lower criterion, but not with sensitivity.
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| 2. |
- Andersson, Linus, 1979-, et al.
(author)
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Effects of Task Demands on Olfactory, Auditory, and Visual Event-Related Potentials Suggest Similar Top-Down Modulation Across Senses
- 2018
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In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 43:2, s. 129-134
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Journal article (peer-reviewed)abstract
- A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.
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| 3. |
- Andersson, Linus, 1979-, et al.
(author)
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Highlighting the large variation in perceived properties of odors over time
- 2017
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In: Chemical Senses. - 0379-864X .- 1464-3553. ; 42:2, s. E26-
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Journal article (peer-reviewed)abstract
- Individuals differ considerably when rating the perceived properties of odors, especially over time. A second glance at previously published data-sets from our laboratory revealed that the same invariant exposure often produced both floor and roof effects. An odor that at the end of the exposure ses-sion was regarded as non-existent by one participant, could border the “absoulte maximum” rating category in another. We provide re-analyses from four exposure studies where we illustrate the perceptual variability over time, and outcomes associated with such ratings. We note that high, compared with low ratings of odor intensity over time is associated with ratings of unpleasantness and symptoms, but also with everyday distress, cognitive performance, autonomous nerv-ous system activity and deviating responses in the so-called pain or saliency matrix of the brain. We bring an open ques-tion to ECRO regarding how this considerable variability should be interpreted, and what the consequenced are for research and for setting exposure limits.
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| 4. |
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| 5. |
- Bonagas, Nadilly, et al.
(author)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 6. |
- Dewrang, Petra, et al.
(author)
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Parental retrospective assessment of development and behavior in Asperger syndrome during the first two years of life
- 2010
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In: Research in Autism Spectrum Disorders. ; 4, s. 461-473
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Journal article (peer-reviewed)abstract
- Development and behavior during the first 2 years of life was assessed retrospectively by the parents to 23 adolescents and young adults with Asperger syndrome and 13 typically developing adolescents and young adults. The groups were matched on chronological age and the participants were within the normal range of intelligence. The questionnaire, symptoms of autism before the age of 2 (SAB-2) comprised seven areas: contact and social activity, responses to sensory perceptions, communication and language/speech, food/ feeding and sleep, play and fixations/rituals, movements and motor skills, and development and behavior. An eighth area of possible early suspicions was also part of the questionnaire. There were significant differences between the groups in all the areas and that the parents in many cases were well aware of anomalies in their children’s behavior at an early age. Food/feeding and sleep and contact and social activity were found to be the areas that caused most concern. The SAB-2 was also judged to be a valid and reliable instrument for retrospective assessment of infants.
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| 7. |
- Dewrang, Petra, et al.
(author)
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Repetitive behaviour and obsessive-compulsive features in Asperger syndrome: Parental and self-reports
- 2011
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In: RESEARCH IN AUTISM SPECTRUM DISORDERS. - 1750-9467. ; 5:3, s. 1176-1186
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Journal article (peer-reviewed)abstract
- Symptoms of repetitive, obsessive and compulsive behaviour were explored in a group of adolescents and young adults with Asperger syndrome and compared to a typically developing group. By means of self-evaluations and an interview regarding such symptoms with the adolescents and young adults and parental evaluations, the parents retrospectively assessed the behaviour of their children from preschool years to middle teens, and the young participants assessed their own behaviour from school years until present time. An anxiety scale was also used. The results revealed no significant differences between the groups on the interview and the anxiety scale. There were, however, significant differences on both the parental and the self-evaluations. Thus, the parents reported that their children had difficulties with repetitive, obsessive–compulsive behaviour, and social interaction from preschool years, and both the parents and the adolescents and young adults reported considerable difficulties in those areas during school years. When comparing the evaluations from the parents and the young participants it was shown that the parents in the Asperger group reported significantly more problems than their children while in the comparison group the parents reported less problems than their children.
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| 8. |
- Green, Alanna C., et al.
(author)
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Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells
- 2023
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In: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5:4, s. 642-659
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Journal article (peer-reviewed)abstract
- Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase–cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a ‘folate trap’. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.
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| 9. |
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| 10. |
- Löfstrand, Sofia, et al.
(author)
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Knyta samman trådarna : resultat från forsknings- och innovationsprogrammet Triple F
- 2024
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In: Sammanställning av referat från Transportforum 2024. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 341-342
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Conference paper (other academic/artistic)abstract
- Triple F är Trafikverkets forskning- och innovationssatsning med syfte att bidra till det svenska godstransportsystemets omställning till fossilfrihet. Programmet pågår 2018-2030 och än så länge har 56 forsknings- och innovationsprojekt initierats för att hantera utmaningarnaEtt mer transporteffektivt samhälle,Överflyttning till energieffektiva och fossilfria fordon, samtSkifte till förnybara drivmedel.I programmet samarbetar näringsliv, akademi och offentlig sektor genom förstudier, forskningsinitiativ och pilotprojekt. 27 projekt har avslutats och resultaten har analyserats och sammanställts för programmet. En metaanalys har genomförts där projekten har kategoriserats, de huvudsakliga slutsatserna från projekten identifierats och sammanställts på en aggregerad nivå med ett antal rubriker. I detta abstract presenteras resultat från Ett mer transporteffektivt samhälle sammanfattat i fyra rubriker. Under Transportforum 2024 ämnas hela programmets resultat att presenteras. Öka medvetenheten om bygglogistikens miljöpåverkan och effektiviseringspotential Cirka 20% av Sveriges totala transporterade vikt transporteras till och från byggprojekt. Utvärderingar visar att antalet lastbilar som anlöper ett byggprojekt kan minskas med mellan 60 och 80%. Det motsvarar en minskning på 6% av antalet godstransporter på väg. Miljökonsekvenserna finns dock inte riktigt med på agendan och dessutom saknas övergripande transportplanering.
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