| 1. |
- Johansson, Ellen, et al.
(författare)
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Revising the embryonic origin of thyroid C cells in mice and humans
- 2015
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 142:20, s. 3519-3528
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Tidskriftsartikel (refereegranskat)abstract
- Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate-mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development implicates a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. In similarity with many gut endoderm derivatives embryonic C cells were found to co-express pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo consistent with a growth-promoting role of Foxa1. Contrasting embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment down-regulated Foxa2 foregoing epithelial-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm, and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.
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| 2. |
- Lyckesvärd, Madeleine Nordén, et al.
(författare)
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Linking loss of sodium-iodide symporter expression to DNA damage
- 2016
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 344:1, s. 120-131
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (< 1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. (C) 2016 Elsevier Inc. All rights reserved.
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| 3. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 4. |
- Almer, Jakob, et al.
(författare)
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Ischemic QRS prolongation as a biomarker of myocardial injury in STEMI patients
- 2019
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Ingår i: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with acute coronary occlusion (ACO) may not only have ischemia-related ST-segment changes but also changes in the QRS complex. It has recently been shown in dogs that a greater ischemic QRS prolongation (IQP) during ACO is related to lower collateral flow. This suggests that greater IQP could indicate more severe ischemia and thereby more rapid infarct development. Therefore, the purpose was to evaluate the relationship between IQP and measures of myocardial injury in patients presenting with acute ST-elevation myocardial infarction (STEMI).METHODS: Seventy-seven patients with first-time STEMI were retrospectively included from the recently published SOCCER trial. All patients underwent a cardiac magnetic resonance (CMR) examination 2-6 days after the acute event. Infarct size (IS), myocardium at risk (MaR), and myocardial salvage index (MSI) were assessed and related to IQP. IQP measures assessed were; computer-generated QRS duration, QRS duration at maximum ST deviation, absolute IQP and relative IQP, all derived from a pre-PCI, 12-lead ECG.RESULTS: Median absolute IQP was 10 ms (range 0-115 ms). There were no statistically significant correlations between measures of IQP and any of the CMR measures of myocardial injury (absolute IQP vs IS, r = 0.03, p = 0.80; MaR, r = -0.01, p = 0.89; MSI, r = -0.05, p = 0.68).CONCLUSIONS: Unlike previous experimental studies, the IQP was limited in patients presenting at the emergency room with first-time STEMI and no correlation was found between IQP and CMR variables of myocardial injury in these patients. Therefore, IQP does not seem to be a suitable biomarker for triaging patients in this clinical context.
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| 5. |
- Aronsson, Mattias, et al.
(författare)
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Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer
- 2017
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Ingår i: British Journal of Surgery. - : WILEY. - 0007-1323 .- 1365-2168. ; 104:8, s. 1078-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer screening can decrease morbidity and mortality. However, there are widespread differences in the implementation of programmes and choice of strategy. The primary objective of this study was to estimate lifelong costs and health outcomes of two of the currently most preferred methods of screening for colorectal cancer: colonoscopy and sensitive faecal immunochemical test (FIT). Methods: A cost-effectiveness analysis of colorectal cancer screening in a Swedish population was performed using a decision analysis model, based on the design of the Screening of Swedish Colons (SCREESCO) study, and data from the published literature and registries. Lifelong cost and effects of colonoscopy once, colonoscopy every 10 years, FIT twice, FIT biennially and no screening were estimated using simulations. Results: For 1000 individuals invited to screening, it was estimated that screening once with colonoscopy yielded 49 more quality-adjusted life-years (QALYs) and a cost saving of (sic)64 800 compared with no screening. Similarly, screening twice with FIT gave 26 more QALYs and a cost saving of (sic)17 600. When the colonoscopic screening was repeated every tenth year, 7 additional QALYs were gained at a cost of (sic)189 400 compared with a single colonoscopy. The additional gain with biennial FIT screening was 25 QALYs at a cost of (sic)154 300 compared with two FITs. Conclusion: All screening strategies were cost-effective compared with no screening. Repeated and single screening strategies with colonoscopy were more cost-effective than FIT when lifelong effects and costs were considered. However, other factors such as patient acceptability of the test and availability of human resources also have to be taken into account.
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| 6. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 9. |
- Carlsson, Emilia, 1983, et al.
(författare)
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Assessing False-Belief Understanding in Children with Autism Using a Computer Application: A Pilot Study.
- 2018
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Ingår i: Journal of psycholinguistic research. - : Springer Science and Business Media LLC. - 1573-6555 .- 0090-6905. ; 47:5, s. 1085-1099
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a False-Belief (FB) understanding task for use on a computer tablet, trying to assess FB understanding in a less social way. It is based on classical FB protocols, and additionally includes a manipulation of language in an attempt to explore the facilitating effect of linguistic support during FB processing. Specifically, the FB task was presented in three auditory conditions: narrative, silent, and interference. The task was assumed to shed new light on the FB difficulties often observed in Autism Spectrum Disorder (ASD). Sixty-eight children with ASD (M=7.5years) and an age matched comparison group with 98 typically developing (TD) children were assessed with the FB task. The children with ASD did not perform above chance level in any condition, and significant differences in success rates were found between the groups in two conditions (silent and narrative), with TD children performing better. We discuss implications, limitations, and further developments.
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| 10. |
- Czolkos, Ilja, et al.
(författare)
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Prediction of wastewater quality using amperometric bioelectronic tongues
- 2016
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 75, s. 375-382
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Tidskriftsartikel (refereegranskat)abstract
- Wastewater samples from a Swedish chemi-thermo-mechanical pulp (CTMP) mill collected at different purification stages in a wastewater treatment plant (WWTP) were analyzed with an amperometric enzyme-based biosensor array in a flow-injection system. In order to resolve the complex composition of the wastewater, the array consists of several sensing elements which yield a multidimensional response. We used principal component analysis (PCA) to decompose the array's responses, and found that wastewater with different degrees of pollution can be differentiated. With the help of partial least squares regression (PLS-R), we could link the sensor responses to the Microtox (R) toxicity parameter, as well as to global organic pollution parameters (COD, BOD, and TOC). From investigating the influences of individual sensors in the array, it was found that the best models were in most cases obtained when all sensors in the array were included in the PLS-R model. We find that fast simultaneous determination of several global environmental parameters characterizing wastewaters is possible with this kind of biosensor array, in particular because of the link between the sensor responses and the biological effect onto the ecosystem into which the wastewater would be released. In conjunction with multivariate data analysis tools, there is strong potential to reduce the total time until a result is yielded from days to a few minutes. (C) 2015 Elsevier B.V. All rights reserved.
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