| 1. |
- Rosendal, Ebba, et al.
(författare)
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Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
- 2022
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
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| 2. |
- Sabale, Ugne, et al.
(författare)
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Healthcare utilization and costs following newly diagnosed type-2 diabetes in Sweden : A follow-up of 38,956 patients in a clinical practice setting
- 2015
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 9:5, s. 330-337
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To describe healthcare resource use patterns and estimate healthcare costs of newly diagnosed Type 2 diabetes mellitus (T2DM) patients in Sweden. Methods: Patients with a newly diagnosed T2DM between 1999 and 2009 were identified from 84 Swedish primary care centres. Healthcare resource use data, excluding pharmaceuticals, were extracted from electronic patient records and a national patient register, and reported as per patient mean number of primary care contacts, laboratory tests and hospitalizations. Per patient mean healthcare costs are reported as annual and cumulative costs. Results: During a median (maximum) of 4.6 (9.0) years follow-up; 38,956 patients (183,513 patient years) on average made 81 primary care contacts, was hospitalized 2.14 times, and took 31 laboratory tests. Mean per patient annual healthcare costs were (sic)4128 (95% CI, 4054-4199) the first year after diagnosis, (sic)2708 (95% CI, 2641-2776) the second year, and (sic)3030 (95% CI, 2854-3204) in year 9 (2012 values). Mean per patient cumulative healthcare costs were (sic)26,503 (95% CI, 26,025-26,970) at 9 years of follow-up. Hospitalizations accounted for the majority of healthcare costs. Conclusions: Although newly diagnosed T2DM patients require a substantial amount of healthcare services in primary care, hospitalizations account for the majority of healthcare costs.
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| 3. |
- Hench, Jürgen, et al.
(författare)
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The Homeobox Genes of Caenorhabditis elegans and Insights into Their Spatio-Temporal Expression Dynamics during Embryogenesis
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Homeobox genes play crucial roles for the development of multicellular eukaryotes. We have generated a revised list of all homeobox genes for Caenorhabditis elegans and provide a nomenclature for the previously unnamed ones. We show that, out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. 14 are highly divergent, lacking an obvious ortholog even in other Caenorhabditis species. One of these homeobox genes encodes 12 homeodomains, while three other highly divergent homeobox genes encode a novel type of double homeodomain, termed HOCHOB. To understand how transcription factors regulate cell fate during development, precise spatio-temporal expression data need to be obtained. Using a new imaging framework that we developed, Endrov, we have generated spatio-temporal expression profiles during embryogenesis of over 60 homeobox genes, as well as a number of other developmental control genes using GFP reporters. We used dynamic feedback during recording to automatically adjust the camera exposure time in order to increase the dynamic range beyond the limitations of the camera. We have applied the new framework to examine homeobox gene expression patterns and provide an analysis of these patterns. The methods we developed to analyze and quantify expression data are not only suitable for C. elegans, but can be applied to other model systems or even to tissue culture systems.
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| 4. |
- Henriksson, Eva, et al.
(författare)
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Differences in estimates of cisplatin-induced cell kill in vitro between colorimetric and cell count/colony assays
- 2006
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Ingår i: In Vitro Cellular & Developmental Biology - Animal. - 1071-2690. ; 42:10, s. 320-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate some bioassays that are different in principle: cell counting, colony forming assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB), crystal violet, and alamarBlue, with respect to their ability to measure cisplatin-induced cell death of in vitro-cultivated squamous cell carcinoma of the head and neck (SCCHN). Cisplatin was applied in concentrations of 1.0, 5.0, 10.0, 50.0, and 100 mu M. The cells were incubated for 1 h, and the cell survival was measured 5 d after treatment. We found the colorimetric assays and cell counting to be comparable. The colony forming assay indicated a higher degree of cell kill compared with the other techniques. Measurement of cell survival after treatment with cisplatin can be done by use of any of the above tested assays. However, the majority of SCCHN cell lines available do not form colonies easily, or at all. Therefore, comparing the chemosensitivity between such cell lines is limited to alternative assays. In this respect, any of the tested colorimetric assays can be used. However, they seem to underestimate cell kill. Cell counting is also an alternative. This technique, however, is time consuming and operator dependent, as in the ease of manual counting, or relatively expensive when counting is performed electronically, compared with the colorimetric assays.
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| 5. |
- Herraiz Adillo, Ángel, et al.
(författare)
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Life's Essential 8 and carotid artery plaques: the Swedish cardiopulmonary bioimage study
- 2023
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Ingår i: Frontiers in Cardiovascular Medicine. - : FRONTIERS MEDIA SA. - 2297-055X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo quantify cardiovascular health (CVH), the American Heart Association (AHA) recently launched an updated construct of the "Life's Simple 7" (LS7) score, the "Life's Essential 8" (LE8) score. This study aims to analyse the association between both CVH scores and carotid artery plaques and to compare the predictive capacity of such scores for carotid plaques.MethodsRandomly recruited participants aged 50-64 years from the Swedish CArdioPulmonary bioImage Study (SCAPIS) were analysed. According to the AHA definitions, two CVH scores were calculated: i) the LE8 score (0, worst CVH; 100, best CVH) and two different versions of the LS7 score [(0-7) and (0-14), 0 indicating the worst CVH]. Ultrasound-diagnosed carotid plaques were classified as no plaque, unilateral, and bilateral plaques. Associations were studied by adjusted multinomial logistic regression models and adjusted (marginal) prevalences, while comparison between LE8 and LS7 scores was performed through receiver operating characteristic (ROC) curves.ResultsAfter exclusions, 28,870 participants remained for analysis (50.3% women). The odds for bilateral carotid plaques were almost five times higher in the lowest LE8 (<50 points) group [OR: 4.93, (95% CI: 4.19-5.79); adjusted prevalence 40.5%, (95% CI: 37.9-43.2)] compared to the highest LE8 (& GE;80 points) group [adjusted prevalence 17.2%, (95% CI: 16.2-18.1)]. Also, the odds for unilateral carotid plaques were more than two times higher in the lowest LE8 group [OR: 2.14, (95% CI: 1.82-2.51); adjusted prevalence 31.5%, (95% CI: 28.9-34.2)] compared to the highest LE8 group [adjusted prevalence 29.4%, (95% CI: 28.3-30.5)]. The areas under ROC curves were similar between LE8 and LS7 (0-14) scores: for bilateral carotid plaques, 0.622 (95% CI: 0.614-0.630) vs. 0.621 (95% CI: 0.613-0.628), P = 0.578, respectively; and for any carotid plaque, 0.602 (95% CI: 0.596-0.609) vs. 0.600 (95% CI: 0.593-0.607), P = 0.194, respectively.ConclusionThe new LE8 score showed inverse and dose-response associations with carotid plaques, particularly bilateral plaques. The LE8 did not outperform the conventional LS7 score, which showed similar ability to predict carotid plaques, especially when scored as 0-14 points. We conclude that both the LE8 and LS7 may be useful in clinical practice for monitoring CVH status in the adult population.
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| 6. |
- Herraiz-Adillo, Ángel, et al.
(författare)
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Life's Essential 8 and Life's Simple 7 in Relation to Coronary Atherosclerosis: Results From the Population-Based SCAPIS Project.
- 2024
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Ingår i: Mayo Clinic proceedings. - : Elsevier. - 1942-5546 .- 0025-6196. ; 99:1, s. 69-80
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Tidskriftsartikel (refereegranskat)abstract
- To examine the associations between the American Heart Association scores ("Life's Essential 8" [LE8] and "Life's Simple 7" [LS7]) and 2 subclinical coronary atherosclerosis indicators: coronary computed tomographic angiography (CCTA)-stenosis and coronary artery calcium (CAC).We included a population-based sample, aged 50 to 64 years, recruited between 2013 and 2018 from the Swedish Cardiopulmonary Bioimage Study (n=24,819, 50.3% women). CCTA-stenosis was graded as no stenosis, stenosis (1%-49%) or severe stenosis (≥50%), whereas CAC was graded as 0, 1 to 99, 100 to 399, or ≥400 Agatston units. Multinomial logistic regression and receiver operating characteristic (ROC) curves were used to study the associations between cardiovascular health scores and subclinical coronary atherosclerosis.Odds ratios (ORs) for CCTA-stenosis and severe CCTA-stenosis between the lowest (<50 points) vs the highest (≥80 points) LE8 group were 4.18 (95% CI, 3.56 to 4.91) and 11.17 (95% CI, 8.36 to 14.93), respectively. For corresponding CAC results, ORs were 3.36 (95% CI, 2.84 to 3.98), 7.72 (95% CI, 6.03 to 9.89), and 14.94 (95% CI, 10.47 to 21.31) for CAC scores of 1 to 99, 100 to 399, and ≥400, respectively. Area under ROC curves for predicting any stenosis were 0.642 (95% CI, 0.635 to 0.649) and 0.631 (95% CI, 0.624 to 0.638, P<.001) for LE8 and LS7, respectively.Our data indicate that LE8 showed a strong, graded, and inverse association with CCTA-stenosis and CAC score. The capacity to predict CCTA-stenosis was comparable between LE8 and LS7, although LE8 had slightly higher prediction capacity of any stenosis. This study provides novel evidence that the LE8 score may be a useful tool for monitoring cardiovascular health.
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| 7. |
- Higueras-Fresnillo, Sara, et al.
(författare)
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Low prevalence of ideal cardiovascular health in the general Swedish population: Results from the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2023
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 51:4, s. 527-530
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the current study was to examine the prevalence of ideal cardiovascular health (iCVH) in the general Swedish middle-aged population. To address this aim, we utilised data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) which is a large Swedish population-based study (N=30,154) that combined comprehensive state-of-the-art imaging technology with clinical examinations and included all iCVH components. A total iCVH score was calculated as the number of iCVH metrics at an ideal level for the seven components and classified as: ideal (> 5 ideal components), intermediate (3-4 ideal components) and poor (<= 2 ideal components). Our results showed that only 18.2% of the population reached ideal status (i.e. > 5 components at the ideal level), whereas 51.9% were classified as intermediate status and 29.9% as poor status of iCVH. Women had a higher prevalence of iCVH status (23.9% vs. 12.0%) and a lower prevalence of poor iCVH status (23.5% vs. 36.8%). Our data may serve as benchmarks for future national and international comparisons and motivate efforts to promote cardiovascular health in the general population, given the strong link between iCVH with all-cause and cardiovascular disease mortality and morbidity.
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| 8. |
- Hildebrandt, Franziska, 1994-, et al.
(författare)
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scDual-Seq of Toxoplasma gondii-infected mouse BMDCs reveals heterogeneity and differential infection dynamics
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells and macrophages are integral parts of the innate immune system and gatekeepers against infection. The protozoan pathogen, Toxoplasma gondii, is known to hijack host immune cells and modulate their immune response, making it a compelling model to study host-pathogen interactions. Here we utilize single cell Dual RNA-seq to parse out heterogeneous transcription of mouse bone marrow-derived dendritic cells (BMDCs) infected with two distinct genotypes of T. gondii parasites, over multiple time points post infection. We show that the BMDCs elicit differential responses towards T. gondii infection and that the two parasite lineages distinctly manipulate subpopulations of infected BMDCs. Co-expression networks define host and parasite genes, with implications for modulation of host immunity. Integrative analysis validates previously established immune pathways and additionally, suggests novel candidate genes involved in host-pathogen interactions. Altogether, this study provides a comprehensive resource for characterizing host-pathogen interplay at high-resolution.
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| 9. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Mohammed, Mubasher, et al.
(författare)
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Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis
- 2024
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The Plasmodium falciparum life cycle includes obligate transition between a human and mosquito host. Gametocytes are responsible for transmission from the human to the mosquito vector where gamete fusion followed by meiosis occurs. To elucidate how male and female gametocytes differentiate in the absence of sex chromosomes, we perform FACS-based cell enrichment of a P. falciparum gametocyte reporter line followed by single-cell RNA-seq. In our analyses we define the transcriptional programs and predict candidate driver genes underlying male and female development, including genes from the ApiAP2 family of transcription factors. A motif-driven, gene regulatory network analysis indicates that AP2-G5 specifically modulates male development. Additionally, genes linked to the inner membrane complex, involved in morphological changes, are uniquely expressed in the female lineage. The transcriptional programs of male and female development detailed herein allow for further exploration of the evolution of sex in eukaryotes and provide targets for future development of transmission blocking therapies.
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