| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 2. |
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| 3. |
- Fukuzawa, Hironobu, et al.
(författare)
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Real-time observation of X-ray-induced intramolecular and interatomic electronic decay in CH2I2
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in real-time. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (∼20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (∼100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation. © 2019, The Author(s).
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| 4. |
- Holland, John, et al.
(författare)
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Use of IC information in Japanese financial firms
- 2012
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Ingår i: Journal of Intellectual Capital. - : Emerald Group Publishing Limited. - 1469-1930 .- 1758-7468. ; 13:4, s. 562-581
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to explore how Japanese Financial Institutions (JFI) acquire and use company intellectual capital (IC) information and other associated intangibles information in their common structured and routine equity investment decisions and how this activity contributed to knowledge creation in the JFIs concerning knowledge of companies, markets and emotions.Design/methodogy/approach – The research employed a multi-case design, using four JFI cases. The JFIs and their IC use were discussed in terms of Nonaka and Toyama’s ’theory of the knowledge creating firm’ (2005). The associated concepts of ‘Ba’, ‘SECI’ and ‘Kata’ were conceptually located within the internal and external order emerging in the cases and were used to analyze JFI knowledge creating behavior. Despite the limits to SECI or Kata processes noted in the cases, these concepts were valuable in analyzing the case data.Findings – Company IC information contributed to earnings estimates and company valuation. Impressionistic and emotional information about intangibles contributed to JFI feelings and confidence in their valuation and information use. Both led to investment decisions. JFI knowledge was an important component of the key interacting and informed contexts used by JFIs to make collective sense of these different but complementary types of information in investment decision making. This created opportunities for improved disclosure and accountability between JFIs and their investee companies. Common patterns of behaviour across the JFIs were counterbalanced by variety and differences noted in JFI behaviour. These included differences in JFI investment philosophy and ‘landscape’.Practical implication – The findings provide important insights in how JFI knowledge creating patterns could limit or progress a common language of communication between companies and markets on the subject of intellectual capital. This could impact on the quality of corporate disclosure and accountability processes. The results will be used in the context of a further development of the Disclosure of Intellectual Assets Based Management in Japan.Originality – The paper combines ideas from the ‘knowledge creating firm’ with conventional ideas of finance, and of disclosure and accountability. This combined theoretical analysis demonstrated a novel and robust theoretical context to interpret the unique Japanese case data, and the distinctive empirical patterns emerging from it.
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| 5. |
- Johanson, Ulf, 1944-, et al.
(författare)
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Japanese Financial Institutions and their use of company intangibles informationin company investment decisions – Ba, SECI, Kata and JFIs as knowledge creatingfirms.
- 2010
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Annan publikation (refereegranskat)abstract
- The purpose of this paper is to explore how Japanese Financial Institutions (JFI)acquire and use company intellectual capital (IC) information and other associated intangiblesinformation in their common structured and routine equity investment decisions and how thisactivity contributed to knowledge creation in the JFIs concerning knowledge of companies,markets and emotions. Company IC information contributed to earnings estimates and companyvaluation. Impressionistic and emotional information about intangibles contributed to JFIfeelings and confidence in their valuation and information use. Both led to investmentdecisions. JFI knowledge was an important component of the key interacting and informedcontexts used by JFIs to make collective sense of these different but complementary types ofinformation in investment decision making. This created opportunities for improveddisclosure and accountability between JFIs and their investee companies. Common patterns ofbehaviour across the JFIs were counterbalanced by variety and differences noted in JFIbehaviour. These included differences in JFI investment philosophy and ‘landscape’.
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| 6. |
- Pérez-Alonso, Marta-Marina, et al.
(författare)
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The calcium sensor CBL7 is required for Serendipita indica-induced growth stimulation in Arabidopsis thaliana, controlling defense against the endophyte and K+ homoeostasis in the symbiosis
- 2022
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Ingår i: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 45:11, s. 3367-3382
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Tidskriftsartikel (refereegranskat)abstract
- Calcium is an important second messenger in plants. The activation of Ca2+ signalling cascades is critical in the activation of adaptive processes in response to environmental stimuli. Root colonization by the growth promoting endophyte Serendipita indica involves the increase of cytosolic Ca2+ levels in Arabidopsis thaliana. Here, we investigated transcriptional changes in Arabidopsis roots during symbiosis with S. indica. RNA-seq profiling disclosed the induction of Calcineurin B-like 7 (CBL7) during early and later phases of the interaction. Consistently, reverse genetic evidence highlighted the functional relevance of CBL7 and tested the involvement of a CBL7-CBL-interacting protein kinase 13 signalling pathway. The loss-of-function of CBL7 abolished the growth promoting effect and affected root colonization. The transcriptomics analysis of cbl7 revealed the involvement of this Ca2+ sensor in activating plant defense responses. Furthermore, we report on the contribution of CBL7 to potassium transport in Arabidopsis. We analysed K+ contents in wild-type and cbl7 plants and observed a significant increase of K+ in roots of cbl7 plants, while shoot tissues demonstrated K+ depletion. Taken together, our work associates CBL7 with an important role in the mutual interaction between Arabidopsis and S. indica and links CBL7 to K+ transport.
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| 7. |
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| 8. |
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| 9. |
- Sakakibara, Y, et al.
(författare)
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Bivalent separation into univalents precedes age-related meiosis I errors in oocytes
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 7550-
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of chromosome segregation errors during meiosis I (MI) in oocytes increases with age. The two-hit model suggests that errors are caused by the combination of a first hit that creates susceptible crossover configurations and a second hit comprising an age-related reduction in chromosome cohesion. This model predicts an age-related increase in univalents, but direct evidence of this phenomenon as a major cause of segregation errors has been lacking. Here, we provide the first live analysis of single chromosomes undergoing segregation errors during MI in the oocytes of naturally aged mice. Chromosome tracking reveals that 80% of the errors are preceded by bivalent separation into univalents. The set of the univalents is biased towards balanced and unbalanced predivision of sister chromatids during MI. Moreover, we find univalents predisposed to predivision in human oocytes. This study defines premature bivalent separation into univalents as the primary defect responsible for age-related aneuploidy.
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| 10. |
- Wang, Yingdi, et al.
(författare)
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Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 465:7297
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Tidskriftsartikel (refereegranskat)abstract
- In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.
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