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- Borne, Kurtis D., et al.
(författare)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
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Ingår i: NATURE CHEMISTRY. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
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Tidskriftsartikel (refereegranskat)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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- Gao, Yu, et al.
(författare)
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Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
- 2022
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Ingår i: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 55:9, s. 1732-1746.e5
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Tidskriftsartikel (refereegranskat)abstract
- Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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- Venkata Ramanarao, Parasa, et al.
(författare)
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Inhibition of Tissue Matrix Metalloproteinases Interferes with Mycobacterium tuberculosis-Induced Granuloma Formation and Reduces Bacterial Load in a Human Lung Tissue Model
- 2017
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Ingår i: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Granulomas are hallmarks of pulmonary tuberculosis (TB) and traditionally viewed as host-protective structures. However, recent evidence suggest that Mycobacterium tuberculosis (Mtb) uses its virulence factors to stimulate the formation of granuloma. In the present study, we investigated the contribution of matrix metalloproteinases (MMPs), host enzymes that cause degradation of the extracellular matrix, to granuloma formation and bacterial load in Mtb-infected tissue. To this end, we used our lung tissue model for TB, which is based on human lung-derived cells and primary human monocyte-derived macrophages. Global inhibition of MMPs in the Mtb-infected tissue model reduced both granuloma formation and bacterial load. The infection caused upregulation of a set of MMPs (MMP1, 3, 9, and 12), and this finding could be validated in lung biopsies from patients with non-cavitary TB. Data from this study indicate that MMP activation contributes to early TB granuloma formation, suggesting that host-directed, MMP-targeted intervention could be considered as adjunct therapy to TB treatment.
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