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- Ambroise, Gorbatchev, et al.
(författare)
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Systematic analysis reveals a functional role for STAMBPL1 in the epithelial-mesenchymal transition process across multiple carcinomas
- 2020
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Ingår i: British Journal of Cancer. - : SPRINGERNATURE. - 0007-0920 .- 1532-1827. ; 123:7, s. 1164-1177
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Tidskriftsartikel (refereegranskat)abstract
- Background Deubiquitinating enzymes (DUBs) are linked to cancer progression and dissemination, yet less is known about their regulation and impact on epithelial-mesenchymal transition (EMT). Methods An integrative translational approach combining systematic computational analyses of The Cancer Genome Atlas cancer cohorts with CRISPR genetics, biochemistry and immunohistochemistry methodologies to identify and assess the role of human DUBs in EMT. Results We identify a previously undiscovered biological function of STAM-binding protein like 1 (STAMBPL1) deubiquitinase in the EMT process in lung and breast carcinomas. We show that STAMBPL1 expression can be regulated by mutant p53 and that its catalytic activity is required to affect the transcription factor SNAI1. Accordingly, genetic depletion and CRISPR-mediated gene knockout of STAMBPL1 leads to marked recovery of epithelial markers, SNAI1 destabilisation and impaired migratory capacity of cancer cells. Reversely, STAMBPL1 expression reprogrammes cells towards a mesenchymal phenotype. A significant STAMBPL1-SNAI1 co-signature was observed across multiple tumour types. Importantly, STAMBPL1 is highly expressed in metastatic tissues compared to matched primary tumour of the same lung cancer patient and its expression predicts poor prognosis. Conclusions Our study provides a novel concept of oncogenic regulation of a DUB and presents a new role and predictive value of STAMBPL1 in the EMT process across multiple carcinomas.
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- Andersson, Malte, 1941, et al.
(författare)
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”Minskande befolkning är inte problemet”
- 2020
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Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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- Cavefors, Oscar, et al.
(författare)
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Regional left ventricular systolic dysfunction associated with critical illness: incidence and effect on outcome
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5415-5423
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Tidskriftsartikel (refereegranskat)abstract
- Aims Left ventricular (LV) dysfunction can be triggered by non-cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. Methods and results In this single-centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF) < 50% and/or regional wall motion abnormalities (RWMA). A cardiologist assessed patients with LV dysfunction for the presence of an acute or chronic cardiac disease, and coronary angiography was performed in high-risk patients. Of the 411 patients included, 100 patients (24%) had LV dysfunction and in 52 (13%) of these patients, LV dysfunction was not attributed to a cardiac disease. Patients with LV dysfunction and non-cardiac disease had higher mortality risk score (Simplified Acute Physiologic Score 3 score), heart rate, noradrenaline doses, and lactate levels as well as decreased EF, stroke volume, and cardiac output compared with patients with normal LV function. Diagnoses most commonly associated with LV dysfunction and non-cardiac disease were sepsis, respiratory insufficiency, major haemorrhage, and neurological disorders. RWMA (n = 40) with or without low EF was more common than global hypokinesia (n = 12) and was reversible in the majority of cases. Twelve patients had a circumferential pattern of RWMA in concordance with Takotsubo syndrome. Crude 30 day mortality was higher in patients with LV dysfunction and non-cardiac disease compared with patients with normal LV function (33% vs. 18%, P = 0.023), but not after risk adjustment (primary outcome) {odds ratio [OR] 1.56 [confidence interval (CI) 0.75-3.39], P = 0.225}. At 90 days, crude mortality was 44% and 22% (P = 0.002), respectively, in these groups. This difference was also significant after risk adjustment [OR 2.40 (CI 1.18-4.88), P = 0.016]. Conclusions Left ventricular systolic dysfunction is commonly triggered by critical illness, is frequently seen as regional hypokinesia, and is linked to an increased risk of death. The prognostic importance of LV dysfunction in critical illness might be underestimated.
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- Eriksson, Anders I., et al.
(författare)
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Cold and warm electrons at comet 67P/Churyumov-Gerasimenko
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Context. Strong electron cooling on the neutral gas in cometary comae has been predicted for a long time, but actual measurements of low electron temperature are scarce. Aims. Our aim is to demonstrate the existence of cold electrons in the inner coma of comet 67P/Churyumov-Gerasimenko and show filamentation of this plasma. Methods. In situ measurements of plasma density, electron temperature and spacecraft potential were carried out by the Rosetta Langmuir probe instrument, LAP. We also performed analytical modelling of the expanding two-temperature electron gas. Results. LAP data acquired within a few hundred km from the nucleus are dominated by a warm component with electron temperature typically 5-10 eV at all heliocentric distances covered (1.25 to 3.83 AU). A cold component, with temperature no higher than about 0.1 eV, appears in the data as short (few to few tens of seconds) pulses of high probe current, indicating local enhancement of plasma density as well as a decrease in electron temperature. These pulses first appeared around 3 AU and were seen for longer periods close to perihelion. The general pattern of pulse appearance follows that of neutral gas and plasma density. We have not identified any periods with only cold electrons present. The electron flux to Rosetta was always dominated by higher energies, driving the spacecraft potential to order -10 V. Conclusions. The warm (5-10 eV) electron population observed throughout the mission is interpreted as electrons retaining the energy they obtained when released in the ionisation process. The sometimes observed cold populations with electron temperatures below 0.1 eV verify collisional cooling in the coma. The cold electrons were only observed together with the warm population. The general appearance of the cold population appears to be consistent with a Haser-like model, implicitly supporting also the coupling of ions to the neutral gas. The expanding cold plasma is unstable, forming filaments that we observe as pulses.
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