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Sökning: WFRF:(Larsen JK)

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  • Thomas, HS, et al. (författare)
  • 2019
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Callaway, EM, et al. (författare)
  • A multimodal cell census and atlas of the mammalian primary motor cortex
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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  • Christiansen, M, et al. (författare)
  • Mutations in the HERG K+-Ion channel: A novel link between long QT syndrome and sudden infant death syndrome
  • 2005
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 95:3, s. 433-434
  • Tidskriftsartikel (refereegranskat)abstract
    • In a 7-week-old infant who experienced sudden infant death syndrome (SIDS), a novel missense mutation was identified in KCNH2, causing a lysine-to-glutamic acid amino acid substitution at position 101 (K101E). KCNH2 codes for the HERG ion channel and mutations in the gene are associated with congenital long-QT syndrome (LQTS), and in the family of this case of SIDS, the mutation was associated with Torsades de pointes tachycardia, making SIDS the most likely outcome of congenital LQTS.
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  • Hunter, KE, et al. (författare)
  • Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity
  • 2022
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:1, s. e048166-
  • Tidskriftsartikel (refereegranskat)abstract
    • Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups.Methods and analysisSystematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events.Ethics and disseminationApproved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases.PROSPERO registration numberCRD42020177408.
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  • Johnson, BJ, et al. (författare)
  • Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol
  • 2022
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:1, s. e048165-
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity.Methods and analysisAnnual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components.Ethics and disseminationThe study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders.PROSPERO registration numberCRD42020177408.
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  • Kjaer, Kurt, et al. (författare)
  • Mezen Bay - a key area for understanding Weichselian glaciations in northern Russia
  • 2003
  • Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 18:1, s. 73-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Sediment successions in coastal cliffs around Mezen Bay, southeastern White Sea, record an unusually detailed history of former glaciations, interstadial marine and fluvial events from the Weichselian. A regional glaciation model for the Weichselian is based on new data from the Mezen Bay area and previously published data from adjacent areas. Following the Mikulinian (Eemian) interglacial a shelf-centred glaciation in the Kara Sea is reflected in proglacial conditions at 100-90 ka. A local ice-cap over the Timan ridge existed between 75 and 65 ka. Renewed glaciation in the Kara Sea spread southwestwards around 60 ka only, interrupted by a marine inundation, before it advanced to its maximum position at about 55-50 ka. After a prolonged ice-free period, the Scandinavian ice-sheet invaded the area from the west and terminated east of Mezen Bay about 17 ka. The previously published evidence of a large ice-dammed lake in the central Arkhangelsk region, Lake Komi, finds no support in this study. Copyright (C) 2003 John Wiley Sons, Ltd.
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  • Larsen, BD, et al. (författare)
  • Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress
  • 2022
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 376:6592, s. 476-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genotoxic therapy such as radiation serves as a frontline cancer treatment, yet acquired resistance that leads to tumor reoccurrence is frequent. We found that cancer cells maintain viability during irradiation by reversibly increasing genome-wide DNA breaks, thereby limiting premature mitotic progression. We identify caspase-activated DNase (CAD) as the nuclease inflicting these de novo DNA lesions at defined loci, which are in proximity to chromatin-modifying CCCTC-binding factor (CTCF) sites. CAD nuclease activity is governed through phosphorylation by DNA damage response kinases, independent of caspase activity. In turn, loss of CAD activity impairs cell fate decisions, rendering cancer cells vulnerable to radiation-induced DNA double-strand breaks. Our observations highlight a cancer-selective survival adaptation, whereby tumor cells deploy regulated DNA breaks to delimit the detrimental effects of therapy-evoked DNA damage.
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  • Norgaard, AW, et al. (författare)
  • Secondary limonene endo-ozonide: A major product from gas-phase ozonolysis of R-(+)-limonene at ambient temperature
  • 2006
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 40:19, s. 3460-3466
  • Tidskriftsartikel (refereegranskat)abstract
    • A 16 s old gas-phase ambient temperature and 1% relative humidity reaction mixture of ozone and R-limonene (ca. 1:10) was sampled on XAD-2 resin followed by pressurized liquid extraction with dichloromethane at ambient temperature. Low temperature on-column injection and gas chromatography (GC) revealed equal amounts of diastereomeric secondary endo-limonene ozonides, in addition to 4-acetyl-l-methyl-cyclohexene (AMCH), 3-isopropyl-6-oxo-heptanal (IPOH), and endo-limonene mono-epoxides. The secondary endo-limonene ozonides began to decrease at extraction temperature above 150 degrees C and were absent at 200 degrees C. Their formation was unaffected by an increase of the relative humidity to 15%. The identification of the secondary limonene ozonides was confirmed by (1) unique consecutive losses of OH and H2O2, respectively, from the protonated quasi-molecular ion in GC-chemical ionization mass spectrometry mode (isobutane), in addition to high resolution mass determination of [M-OH] and [M-H2O2] ions in EI mode; (2) comparison of mass spectral data to that of synthesized secondary endo-limonene ozonides; and (3) oxidation of dimethyl sulfide to dimethyl sulfoxide and subsequent increase of IPOH.
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