| 1. |
- Sungnak, W., et al.
(author)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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In: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Journal article (peer-reviewed)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 2. |
- Kurzawa-Akanbi, M., et al.
(author)
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Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina
- 2022
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 11:12
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Journal article (peer-reviewed)abstract
- Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient-specific RPE cells with the Complement Factor H Y402H high-risk polymorphism to perform a comprehensive analysis of extracellular vesicles (EVs), their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced polarised EV secretion. Multi-omics analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids, which mediate key AMD features including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. Moreover, AMD RPE EVs induce amyloid fibril formation, revealing their role in drusen formation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the acquisition of AMD features such as stress vacuoles, cytoskeletal destabilization and abnormalities in the morphology of the nucleus. Retinal organoid treatment with apical AMD RPE EVs leads to disrupted neuroepithelium and the appearance of cytoprotective alpha B crystallin immunopositive cells, with some co-expressing retinal progenitor cell markers Pax6/Vsx2, suggesting injury-induced regenerative pathways activation. These findings indicate that AMD RPE EVs are potent inducers of AMD phenotype in the neighbouring RPE and retinal cells.
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| 3. |
- Boström, Hanna L. B., et al.
(author)
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How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study
- 2024
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In: Advanced Materials. - 0935-9648 .- 1521-4095. ; 36:15
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Journal article (peer-reviewed)abstract
- Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues. This is crucial, as it hampers the research and commercialization of affected MOFs. Here, it presents the first-ever interlaboratory study of the synthetic reproducibility of two Zr-porphyrin MOFs, PCN-222 and PCN-224, to investigate the scope of this problem. For PCN-222, only one sample out of ten was phase pure and of the correct symmetry, while for PCN-224, three are phase pure, although none of these show the spatial linker order characteristic of PCN-224. Instead, these samples resemble dPCN-224 (disordered PCN-224), which has recently been reported. The variability in thermal behavior, defect content, and surface area of the synthesised samples are also studied. The results have important ramifications for field of metal-organic frameworks and their crystallization, by highlighting the synthetic challenges associated with a multi-variable synthesis space and flat energy landscapes characteristic of MOFs. It performed an interlaboratory study of the synthesis of the metal-organic frameworks (MOFs) PCN-222 and PCN-224. Ten participants independently synthesized the two MOFs and the products are analyzed, primarily by X-ray diffraction. The success rates are low (one-three samples corresponding to a pure sample of the correct phase), thus highlighting the problems with irreproducibility in MOF synthesis. image
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| 4. |
- Muus, Christoph, et al.
(author)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Journal article (peer-reviewed)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 5. |
- Queen, C, et al.
(author)
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Multi-method analysis of gender differences in psychological distress among the elderly during COVID
- 2022
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In: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 32:Supplement_3
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Journal article (peer-reviewed)abstract
- As COVID swept through Europe, and the world, with high rates of illness and death, so did symptoms of anxiety, depression, post-traumatic stress disorder, stress, and psychological distress. This study examines the relationship between gender and psychological distress among Latvians over 50 years old within the first 6 months of the COVID-19 pandemic. Data from Wave 8 COVID-19 data of the Survey of Health, Aging, and Retirement in Europe (SHARE) as an early data version of the SHARE Corona survey conducted between June and August 2020. It features the data collected by telephone (CATI) on topics related to COVID-19 for a large sub-sample of SHARE panel respondents. This study examined a sample of 980 adults over 50 years old in Latvia. Bivariate analysis were performed utilizing the Pearson chi-square test for association to examine differences in symptoms of psychological distress by gender during the first six months of the COVID-19 pandemic. Level of significance was determined by the p-value test statistic. Alpha level was established at .05. A chi-square test for association shows that there were statistically relationships between gender and feeling nervous (X2 (2, N = 976) = 22.11, p < .001), feeling depressed (X2 (3, N = 976) = 10.95, p < .01), and trouble sleeping (X2 (2, N = 976) = 20.40, p < .001). This study rejects the null hypothesis that no differences exist between the genders, as women reported greater psychological distress during the first 6 months of the COVID-19 pandemic. Additional multi-method analysis is consistent with these findings and concludes that this is due to the greater concern women report for family, and the burden which placed limitations on meeting their children and grandchildren.
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