| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 7. |
- Regev, A, et al.
(författare)
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The Human Cell Atlas
- 2017
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Ingår i: eLife. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 9. |
- Aguilera-Lizarraga, J., et al.
(författare)
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Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune-related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods: A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results: A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3-fold change), prostaglandin synthase PTGS2 (2.1-fold change), and the G-protein-coupled receptor MRGPRX2 (10.7-fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno-active” IBS patients in the other patient cohort. Conclusion: A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti-inflammatory therapy remains to be investigated. © 2019 John Wiley & Sons Ltd
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| 12. |
- Besnard, Simon, et al.
(författare)
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Quantifying the effect of forest age in annual net forest carbon balance
- 2018
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Forests dominate carbon (C) exchanges between the terrestrial biosphere and the atmosphere on land. In the long term, the net carbon flux between forests and the atmosphere has been significantly impacted by changes in forest cover area and structure due to ecological disturbances and management activities. Current empirical approaches for estimating net ecosystem productivity (NEP) rarely consider forest age as a predictor, which represents variation in physiological processes that can respond differently to environmental drivers, and regrowth following disturbance. Here, we conduct an observational synthesis to empirically determine to what extent climate, soil properties, nitrogen deposition, forest age and management influence the spatial and interannual variability of forest NEP across 126 forest eddy-covariance flux sites worldwide. The empirical models explained up to 62% and 71% of spatio-temporal and across-site variability of annual NEP, respectively. An investigation of model structures revealed that forest age was a dominant factor of NEP spatio-temporal variability in both space and time at the global scale as compared to abiotic factors, such as nutrient availability, soil characteristics and climate. These findings emphasize the importance of forest age in quantifying spatio-temporal variation in NEP using empirical approaches.
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| 13. |
- Bianco, Paolo, et al.
(författare)
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Regulation of stem cell therapies under attack in Europe: for whom the bell tolls
- 2013
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Ingår i: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 32:11, s. 1489-1495
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non-medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context-social, financial, medical, legal-in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of 'translational medicine'. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients.
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| 14. |
- Boj, Sylvia F, et al.
(författare)
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Organoid models of human and mouse ductal pancreatic cancer
- 2015
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Ingår i: Cell. - : Cell press. - 0092-8674 .- 1097-4172. ; 160:1-2, s. 324-338
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
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| 15. |
- Clevers, Egbert, et al.
(författare)
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Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
- 2018
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.
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| 16. |
- Clevers, Egbert, et al.
(författare)
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Gastrointestinal symptoms in office workers are predicted by psychological distress and short sleep duration
- 2020
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Gastrointestinal (GI) symptoms can be triggered by several lifestyle factors, including psychological distress, short sleep duration, and diet. It is poorly known which physiological mechanisms are involved, but the autonomic nervous system (as a key mediator of the stress response) is a likely candidate. We aimed to investigate the associations between selected lifestyle factors, measures of stress physiology, and GI symptoms. Methods: This is a longitudinal study of 1002 office employees (52% male, mean age 39 +/- 10 years), who were asked to report their GI symptoms, psychological distress, sleep times, and intake of caffeine, alcohol, and soft drinks for 5 days. Skin conductance, heart rate / variability, and acceleration were automatically recorded using wearable sensors. 850 participants from this study were eligible for analysis. We computed within-person correlations between the variables and used mediation analysis to test causal models. Results: Sleep duration(rho = -0.12, p < 0.001) and psychological distress (rho = 0.19, p < 0.001) were significantly though weakly associated with GI symptoms. The physiological variables were not or weakly associated with GI symptoms in this study. The association between sleep duration and GI symptoms was largely mediated by psychological distress (61%). Conclusions: Short sleep and psychological distress predict GI symptoms in office workers. Further research is needed to unravel the physiological mechanisms mediate this association.
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