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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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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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- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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- James, Ella L., et al.
(författare)
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Playing the computer game Tetris prior to viewing traumatic film material and subsequent intrusive memories : Examining proactive interference
- 2016
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Ingår i: Journal of Behavior Therapy and Experimental Psychiatry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-7916 .- 1873-7943. ; 53, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Visuospatial working memory (WM) tasks performed concurrently or after an experimental trauma (traumatic film viewing) have been shown to reduce subsequent intrusive memories (concurrent or retroactive interference, respectively). This effect is thought to arise because, during the time window of memory consolidation, the film memory is labile and vulnerable to interference by the WM task. However, it is not known whether tasks before an experimental trauma (i.e. proactive interference) would also be effective. Therefore, we tested if a visuospatial WM task given before a traumatic film reduced intrusions. Findings are relevant to the development of preventative strategies to reduce intrusive memories of trauma for groups who are routinely exposed to trauma (e.g. emergency services personnel) and for whom tasks prior to trauma exposure might be beneficial. Methods: Participants were randomly assigned to 1 of 2 conditions. In the Tetris condition (n = 28), participants engaged in the computer game for 11 min immediately before viewing a 12-min traumatic film, whereas those in the Control condition (n = 28) had no task during this period. Intrusive memory frequency was assessed using an intrusion diary over 1-week and an Intrusion Provocation Task at 1 week follow-up. Recognition memory for the film was also assessed at 1-week. Results: Compared to the Control condition, participants in the Tetris condition did not report statistically significant difference in intrusive memories of the trauma film on either measure. There was also no statistically significant difference in recognition memory scores between conditions. Limitations: The study used an experimental trauma paradigm and findings may not be generalizable to a clinical population. Conclusions: Compared to control, playing Tetris before viewing a trauma film did not lead to a statistically significant reduction in the frequency of later intrusive memories of the film. It is unlikely that proactive interference, at least with this task, effectively influences intrusive memory development. WM tasks administered during or after trauma stimuli, rather than proactively, may be a better focus for intrusive memory amelioration. (C) 2015 The Authors. Published by Elsevier Ltd.
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- Joshy, G, et al.
(författare)
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Predicting 7-year mortality for use with evidence-based guidelines for Prostate-Specific Antigen (PSA) testing: findings from a large prospective study of 123 697 Australian men
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:12, s. e022613-
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Tidskriftsartikel (refereegranskat)abstract
- To develop and validate a prediction model for short-term mortality in Australian men aged ≥45years, using age and self-reported health variables, for use when implementing the Australian Clinical Practice Guidelines for Prostate-Specific Antigen (PSA) Testing and Early Management of Test-Detected Prostate Cancer. Implementation of one of the Guideline recommendations requires an estimate of 7-year mortality.DesignProspective cohort study using questionnaire data linked to mortality data.SettingMen aged ≥45years randomly sampled from the general population of New South Wales, Australia, participating in the 45 and Up Study.Participants123 697 men who completed the baseline postal questionnaire (distributed from 1 January 2006 to 31 December 2008) and gave informed consent for follow-up through linkage of their data to population health databases.Primary outcome measuresThe primary outcome was all-cause mortality.Results12 160 died during follow-up (median=5.9 years). Following age-adjustment, self-reported health was the strongest predictor of all-cause mortality (C-index: 0.827; 95% CI 0.824 to 0.831). Three prediction models for all-cause mortality were validated, with predictors: Model-1: age group and self-rated health; Model-2: variables common to the 45 and Up Study and the Australian Health Survey and subselected using stepwise regression and Model-3: all variables selected using stepwise regression. Final predictions calibrated well with observed all-cause mortality rates. The 90th percentile for the 7-year mortality risks ranged from 1.92% to 83.94% for ages 45–85 years.ConclusionsWe developed prediction scores for short-term mortality using age and self-reported health measures and validated the scores against national mortality rates. Along with age, simple measures such as self-rated health, which can be easily obtained without physical examination, were strong predictors of all-cause mortality in the 45 and Up Study. Seven-year mortality risk estimates from Model-3 suggest that the impact of the mortality risk prediction tool on men’s decision making would be small in the recommended age (50–69 years) for PSA testing, but it may discourage testing at older ages.
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