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| 2. |
- 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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| 3. |
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| 4. |
- Bakken, TE, et al.
(författare)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Tidskriftsartikel (refereegranskat)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 7. |
- Ruseckas, Arvydas, et al.
(författare)
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Conformations and Photophysics of a Stilbene Dimer.
- 2003
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Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 107:40, s. 8029-8034
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Tidskriftsartikel (refereegranskat)abstract
- Photophysical studies of pseudo-p-distyryl[2.2]paracyclophane, a model molecule of a stilbene dimer arranged in a brick-wall geometry, in tetrahydrofurane solution indicate the existence of at least two conformers in the ground state. The conformer A with the smallest optical gap of 3 eV has a short radiative lifetime of 3.3 ns, while the conformer B with an optical gap about 0.3 eV larger is much more abundant in solution and its radiative lifetime is about 10 times longer. Ab initio calculations show that the ground-state energy has a shallow minimum with respect to the torsional angle between the styryl side group and the paracyclophane core around the zero position, with the lowest energy conformation at a torsional angle of -21. On this basis, A and B are assigned to flat and twisted conformations, respectively. Conformer B shows a partial decay of excited-state absorption and fluorescence with a time constant ranging from 5 to 30 ps, depending on excitation photon energy. We attribute this to isomerization of the stilbene moiety, which initially keeps conjugation in the ground state. The isomerization product is long-lived and tends to accumulate in solution.
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| 8. |
- Hua, Weijie, et al.
(författare)
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Transient X-ray Absorption Spectral Fingerprints of the S1 Dark State in Uracil
- 2019
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 10:22, s. 7172-7178
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Tidskriftsartikel (refereegranskat)abstract
- Low-lying dark nÏ€∗ states play an important role in many photophysical and photochemical processes of organic chromophores. Transient X-ray absorption spectroscopy (TXAS) provides a powerful technique for probing the dynamics of valence states by exciting the electrons into high-lying core excited states. We employ multiconfigurational self-consistent field calculations to investigate the TXAS of uracil along its nonradiative photodecay pathways. An open issue is whether dark nÏ€∗ state S1 (n is the lone pair localized on an oxygen atom) is accessible when bright ππ∗ state S2 is selectively excited. Vertical core excitations were calculated along the potential energy surfaces of the three lowest states, S0-S2, interpolated between two minima and two minimum-energy conical intersections. Computed TXAS data from the C, N, and O K edges show distinct spectral fingerprints of the dark state in all spectral regimes. At the O 1s edge, the nÏ€∗ state has a very strong absorption at 526-527 eV, while at the C (N) 1s edge, by contrast, there is almost zero (very weak) absorption at 279-282 eV (397-398 eV). All K-edge spectra can be used to sensitively detect the dark states. Our proposed O 1s feature has already been observed in a recent TXAS experiment with thymine. Natural transition orbital analysis is used to interpret all dominant features of the three lowest-valence states along the reaction coordinate and reveal some important valence fine-structure information from the core excitation.
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| 9. |
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