| 1. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 2. |
- Andersson, Niklas, et al.
(författare)
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Methodology for fast development of digital solutions in integrated continuous downstream processing
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Ingår i: Biotechnology and Bioengineering. - 0006-3592.
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Tidskriftsartikel (refereegranskat)abstract
- The methodology for production of biologics is going through a paradigm shift from batch-wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot-print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on-line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real-time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real-time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model-based and plant-wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model-based batch-to-batch control.
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| 3. |
- Backman, Max, et al.
(författare)
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Extending the immune phenotypes of lung cancer: Oasis in the desert
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Tumor infiltrating immune cells are key elements of the tumor microenvironment and mediate the anti-tumor effects of immunotherapy. The aim of the study was to characterize patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to tumor mutations and clinicopathological parameters. Methods: Lymphocytes (CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+) and PD-L1+ were annotated on a tissue microarray including 357 operated NSCLC cases. Somatic mutations and tumor mutational burden were analyzed by targeted sequencing for 82 genes, and transcriptomic immune patterns were established in 197 patients based on RNAseq data. Results: We identified somatic mutations (TP53, NF1, KEAP1, CSMD3, LRP1B) that correlated with specific immune cell infiltrates. Hierarchical clustering revealed four immune classes: with (1) high immune cell infiltration (“inflamed”), (2) low immune cell infiltration (“desert”), (3) a mixed phenotype, and (4) a new phenotype with an overall muted inflammatory cell pattern but with an imprint of NK and plasma cells. This latter class exhibited low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, TGFB1), but was linked to better survival and therefore designated “oasis”. Otherwise, the four immune classes were not related to the presence of specific mutations (EGFR, KRAS, TP53) or histologic subtypes. Conclusion: We present a compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC and identified the novel immune class “oasis”. The immune classification helps to better define the immunogenic potency of NSCLC in the era of immunotherapy.
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| 4. |
- Backman, Max, et al.
(författare)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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| 5. |
- Balfors, Berit, Professor, 1958-, et al.
(författare)
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Strategisk miljöbedömning för nationell transportplanering med fokus på inriktningsunderlaget
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport utgör ett inspel till Trafikverket i en analys om hur strategisk miljöbedömning kan användas i den statliga transportplaneringens tidiga skeden med fokus på inriktningsunderlaget. Rapporten är framtaget inom projektet ”TRAMP- Är långsiktig transportplanering och miljöbedömning kompatibla processer?” som är ett forsknings- och innovationsprojekt (FoI), finansierat av Trafikverket under perioden 2017 - 2019. Deltagande forskare i projektet är Berit Balfors och Ulrika Gunnarsson-Östling, KTH, Kristina Lundberg och Tobias Robinson, Ecoloop, Karolina Isaksson och Linnea Eriksson, VTI.FoI-projektet har planerats för att successivt leverera användbart underlag till Trafikverket. Föreliggande rapport är ett underlag inför Trafikverkets arbete med att ta fram ett inriktningsunderlag.
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| 6. |
- Claesson, Elin, 1989, et al.
(författare)
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The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
- 2020
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Ingår i: eLife. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
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| 7. |
- da Silva, Marisa, et al.
(författare)
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Cohort profile : The Obesity and Disease Development Sweden (ODDS) study, a pooled cohort
- 2024
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Ingår i: BMJ Open. - 2044-6055. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The Obesity and Disease Development Sweden (ODDS) study was designed to create a large cohort to study body mass index (BMI), waist circumference (WC) and changes in weight and WC, in relation to morbidity and mortality.PARTICIPANTS: ODDS includes 4 295 859 individuals, 2 165 048 men and 2 130 811 women, in Swedish cohorts and national registers with information on weight assessed once (2 555 098 individuals) or more (1 740 761 individuals), in total constituting 7 733 901 weight assessments at the age of 17-103 years in 1963-2020 (recalled weight as of 1911). Information on WC is available in 152 089 men and 212 658 women, out of whom 108 795 have repeated information on WC (in total 512 273 assessments). Information on morbidity and mortality was retrieved from national registers, with follow-up until the end of 2019-2021, varying between the registers.FINDINGS TO DATE: Among all weight assessments (of which 85% are objectively measured), the median year, age and BMI (IQR) is 1985 (1977-1994) in men and 2001 (1991-2010) in women, age 19 (18-40) years in men and 30 (26-36) years in women and BMI 22.9 (20.9-25.4) kg/m 2 in men and 23.2 (21.2-26.1) kg/m 2 in women. Normal weight (BMI 18.5-24.9 kg/m 2) is present in 67% of assessments in men and 64% in women and obesity (BMI≥30 kg/m 2) in 5% of assessments in men and 10% in women. The median (IQR) follow-up time from the first objectively measured or self-reported current weight assessment until emigration, death or end of follow-up is 31.4 (21.8-40.8) years in men and 19.6 (9.3-29.0) years in women. During follow-up, 283 244 men and 123 457 women died. FUTURE PLANS: The large sample size and long follow-up of the ODDS Study will provide robust results on anthropometric measures in relation to risk of common diseases and causes of deaths, and novel findings in subgroups and rarer outcomes.
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| 8. |
- Eriksson, Linnea, 1984-, et al.
(författare)
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A climate report gone missing : power mechanisms in Swedish national transport planning
- 2024
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Ingår i: European Planning Studies. - : Routledge. - 0965-4313 .- 1469-5944. ; 32:6, s. 1423-1441
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Tidskriftsartikel (refereegranskat)abstract
- While the technological development of vehicles and fuels is not adequate to meet current climate mitigation targets, infrastructure development also plays an important role in transforming the transport system. Previous studies have argued that conventional infrastructure planning is incapable of implementing climate mitigation. The aim of the paper is to provide insights into power means and mechanisms that counteract integration of climate mitigation targets in infrastructure planning. This is done by an in-depth case study of current Swedish national transport planning. This case provides a rich illustration of a situation with high political ambitions regarding climate mitigation on the one hand, and power mechanisms and resistance with regard to climate goals during the planning process on the other. The case is analysed using the perspective of power circuits and shows how forecasting works as an obligatory passage point, sorting in and out which analyses will be part of the decision-making material. Analyses which do not fit the forecasting model are dismissed from planning. The conclusion is that as long as the transport infrastructure planning practice is dependent on forecasting as the only central analysis there will be difficulties in changing the scope of infrastructure planning and making climate goals central for transport planning.
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| 9. |
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| 10. |
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| 11. |
- Gustavsson, Emil, 1987, et al.
(författare)
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Modulation of Structural Heterogeneity Controls Phytochrome Photoswitching
- 2020
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 118:2, s. 415-421
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes sense red/far-red light and control many biological processes in plants, fungi, and bacteria. Although the crystal structures of dark- and light-adapted states have been determined, the molecular mechanisms underlying photoactivation remain elusive. Here, we demonstrate that the conserved tongue region of the PHY domain of a 57-kDa photosensory module of Deinococcus radiodurans phytochrome changes from a structurally heterogeneous dark state to an ordered, light-activated state. The results were obtained in solution by utilizing a laser-triggered activation approach detected on the atomic level with high-resolution protein NMR spectroscopy. The data suggest that photosignaling of phytochromes relies on careful modulation of structural heterogeneity of the PHY tongue.
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| 12. |
- Henry, Léocadie, et al.
(författare)
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Real-time tracking of protein unfolding with time-resolved x-ray solution scattering
- 2020
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Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 7:5
-
Tidskriftsartikel (refereegranskat)abstract
- The correct folding of proteins is of paramount importance for their function, and protein misfolding is believed to be the primary cause of a wide range of diseases. Protein folding has been investigated with time-averaged methods and time-resolved spectroscopy, but observing the structural dynamics of the unfolding process in real-time is challenging. Here, we demonstrate an approach to directly reveal the structural changes in the unfolding reaction. We use nano- to millisecond time-resolved x-ray solution scattering to probe the unfolding of apomyoglobin. The unfolding reaction was triggered using a temperature jump, which was induced by a nanosecond laser pulse. We demonstrate a new strategy to interpret time-resolved x-ray solution scattering data, which evaluates ensembles of structures obtained from molecular dynamics simulations. We find that apomyoglobin passes three states when unfolding, which we characterize as native, molten globule, and unfolded. The molten globule dominates the population under the conditions investigated herein, whereas native and unfolded structures primarily contribute before the laser jump and 30 mu s after it, respectively. The molten globule retains much of the native structure but shows a dynamic pattern of inter-residue contacts. Our study demonstrates a new strategy to directly observe structural changes over the cause of the unfolding reaction, providing time- and spatially resolved atomic details of the folding mechanism of globular proteins. (C) 2020 Author(s).
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| 13. |
- Huss, Linnea, et al.
(författare)
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The Vitamin D Receptor as a Prognostic Marker in Breast Cancer-A Cohort Study
- 2024
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Ingår i: Nutrients. - 2072-6643. ; 16:7, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has indicated an association between the presence of the vitamin D receptor (VDR) in breast cancer tissue and a favorable prognosis. This study aimed to further evaluate the prognostic potential of VDR located in the nuclear membrane or nucleus (liganded). The VDR protein levels were analyzed using immunohistochemistry in tumor samples from 878 breast cancer patients from Lund, Sweden, included in the Breast Cancer and Blood Study (BCBlood) from October 2002 to June 2012. The follow-up for breast cancer events and overall survival was recorded until 30 June 2019. Univariable and multivariable survival analyses were conducted, both with complete case data and with missing data imputed using multiple imputation by chained equations (MICE). Tumor-specific positive nuclear membrane VDR(num) staining was associated with favorable tumor characteristics and a longer breast cancer free interval (BCFI; HR: 0.64; 95% CI: 0.44-0.95) and overall survival (OS; HR: 0.52; 95% CI: 0.34-0.78). Further analyses indicated that VDRnum status also was predictive of overall survival when investigated in relation to ER status. There were significant interactions between VDR and invasive tumor size (Pinteraction = 0.047), as well as mode of detection (Pinteraction = 0.049). VDRnum was associated with a longer BCFI in patients with larger tumors (HR: 0.36; 95% CI: 0.14-0.93) or clinically detected tumors (HR: 0.28; 95% CI: 0.09-0.83), while no association was found for smaller tumors and screening-detected tumors. Further studies are suggested to confirm our results and to evaluate whether VDR should and could be used as a prognostic and targetable marker in breast cancer diagnostics.
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| 14. |
- Ihalainen, J. A., et al.
(författare)
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Chromophore-Protein Interplay during the Phytochrome Photocycle Revealed by Step-Scan FTIR Spectroscopy
- 2018
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:39, s. 12396-12404
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Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins regulate many photo-responses of plants and microorganisms. Light absorption causes isomerization of the biliverdin chromophore, which triggers a series of structural changes to activate the signaling domains of the protein. However, the structural changes are elusive, and therefore the molecular mechanism of signal transduction remains poorly understood. Here, we apply twocolor step-scan infrared spectroscopy to the bacteriophytochrome from Deinococcus radiodurans. We show by recordings in H2O and D2O that the hydrogen bonds to the biliverdin D-ring carbonyl become disordered in the first intermediate (Lumi-R) forming a dynamic microenvironment, then completely detach in the second intermediate (Meta-R), and finally reform in the signaling state (Pfr). The spectra reveal via isotope labeling that the refolding of the conserved "PHY-tongue" region occurs with the last transition between Meta-R and Pfr. Additional changes in the protein backbone are detected already within microseconds in Lumi-R Aided by molecular dynamics simulations, we find that a strictly conserved salt bridge between an arginine of the PHY tongue and an aspartate of the chromophore binding domains is broken in Lumi-R and the arginine is recruited to the D-ring C=O. This rationalizes how isomerization of the chromophore is linked to the global structural rearrangement in the sensory receptor. Our findings advance the structural understanding of phytochrome photoactivation.
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| 15. |
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| 16. |
- Isaksson, Karolina, 1973-, et al.
(författare)
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Att integrera klimatmål i nationell transportplanering : maktdynamik som formar planeringens taktik : slutrapport från projektet Klimatfrågans integrering i nationell transportplanering – en maktanalys
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med detta projekt har varit att fördjupa kunskapen om nationell transportplanering, med fokus på vilka förutsättningar som finns att integrera klimatmål i strategisk planering på transportområdet. Vi har fokuserat på processen för planering av nationell transportinfrastruktur (även kallad nationell planering). Denna process ligger till grund för långsiktiga beslut, handlingsinriktningar och investeringar när det gäller utvecklingen av nationell transportinfrastruktur, och är ett sammanhang av stor vikt för hela transportsystemets utveckling. Det handlar inte minst om att nå ett mer transporteffektivt samhälle, som ingår som ett av tre ben i regeringens aktuella strategi för transportsystemets klimatomställning. Studien har genomförts med fokus på: (i) Aktörer och processer som formar inriktningen för den långsiktiga nationella planeringen. (ii) Idéer, perspektiv och förgivettaganden som villkorar hur klimatmål integreras och ges mening i nationell planering. (iii) Spänningar och konflikter kopplat till klimatmål och klimatomställning. De analyser som har gjorts i projektet grundas i empiriskt material från två nationella transportinfrastrukturplaneringprocesser; dels den som bedrevs mellan 2015-2017 och som avsåg nationell plan 2018-2029, dels den nu pågående omgången som inleddes 2020 och som omfattar perioden 2022-2033. Dessa två planomgångar har studerats genom kvalitativa intervjuer och analyser av policy- och planeringsdokument. Analysen inspireras av ett maktteoretiskt ramverk med fokus på främst diskursiv makt, men inkluderar också maktanalys utifrån ett aktörsperspektiv.
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| 17. |
- Isaksson, Karolina, 1973-, et al.
(författare)
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Discursive power dynamics affecting how climate targets are framed and integrated in national transport planning : The case of Sweden
- 2023
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Ingår i: Discourse Analysis in Transport and Urban Development. - : Edward Elgar Publishing Ltd.. - 9781802207194 - 9781802207200 ; , s. 39-51
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Discursive power dynamics are explored that shape dominant meanings and understandings related to climate mitigation in national transport policy and planning. The research is carried out as a Foucauldian-inspired discourse analysis of policy and planning documents from national transport planning in Sweden, focusing on the recent and ongoing rounds of national transport planning. The meanings, problem definitions and suggestions about possible and reasonable ways forward for climate mitigation are examined within the documentation, with specific attention given to the framing of strategic choices and priorities for the future. Five dominant themes are identified on climate mitigation that permeate the documents from national transport policy and planning. Altogether, the discursive framings and meaning making has led to a situation where deep political issues and strategic choices are being avoided and not dealt with explicitly. The chapter concludes with a brief discussion on the need for a changed practice of transport politics and planning.
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| 18. |
- Isaksson, Karolina, et al.
(författare)
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Layering and parallel policy making : Complementary concepts for understanding implementation challenges related to sustainable mobility
- 2017
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Ingår i: Transport Policy. - : Elsevier BV. - 0967-070X .- 1879-310X. ; 53, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- This paper is focused on implementation challenges related to the integration of sustainable mobility in strategic local/regional land use and transport planning. The work was based on a case study of Stockholm, Sweden, focusing on four current plans and strategies of key importance for sustainable mobility. We identify and discuss implementation challenges related to sustainable mobility using a theoretical framework from the policy integration literature, with a focus on the dimensions of “layering”, “drift” and “exhaustion” (Rayner & Howlett 2009).The empirical analysis led us to identify a complementary dimension which we call ‘Parallel policy making’. The parallel policy making reflects a fundamental lack of integration of sustainable mobility in policies and plans of strategic importance, which hinders effective policy integration. Altogether, we conclude that a better insight into the practice of parallel policy making is crucial for development of more effective implementation strategies for sustainable mobility in Stockholm and elsewhere.
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| 19. |
- Isaksson, Linnéa, et al.
(författare)
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Cell-Free Protein Synthesis of Small Intrinsically Disordered Proteins for NMR Spectroscopy
- 2020
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Ingår i: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer US. - 1940-6029. ; 2141, s. 233-245
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free protein synthesis (CFPS) is an established method to produce recombinant proteins and has been used in a wide variety of applications. The use of CFPS has almost from the onset been favorably linked to the production of isotopically labelled proteins for NMR spectroscopy as the resulting labelling of the produced protein is defined by the chosen amino acids during reaction setup. Here we describe how to set up production and isotopic labelling of small intrinsically disordered proteins (IDPs) for NMR spectroscopy applications using an E. coli-based CFPS system in batch mode.
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| 20. |
- Isaksson, Linnéa, et al.
(författare)
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Expression screening of membrane proteins with cell-free protein synthesis.
- 2012
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Ingår i: Protein expression and purification. - : Elsevier BV. - 1096-0279 .- 1046-5928. ; 82:1, s. 218-25
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Tidskriftsartikel (refereegranskat)abstract
- Detailed biophysical studies of integral membrane proteins are often hampered by sample preparation difficulties. Membrane proteins are typically difficult to express in sufficient amounts to enable the use of demanding techniques such as nuclear magnetic resonance and X-ray crystallography for structural biology. Here, we show that an inexpensive batch-based cell-free expression system can be a viable alternative for production of a wide range of different membrane proteins, both of prokaryotic and eukaryotic origin. Out of 38 tested protein constructs, 37 express at levels suitable for structural biology, i.e. enough to produce several milligrams of protein routinely and without excessive costs. This success rate was not anticipated and is even more impressive considering that more than half of the expressed proteins where of mammalian origin. A detergent screen identified Brij-58 as the, in general, most successful choice for co-translational solubilization of the expressed proteins.
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| 21. |
- Isaksson, Linnéa, et al.
(författare)
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Highly Efficient NMR Assignment of Intrinsically Disordered Proteins: Application to B- and T Cell Receptor Domains
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- We present an integrated approach for efficient characterization of intrinsically disordered proteins. Batch cell-free expression, fast data acquisition, automated analysis, and statistical validation with data resampling have been combined for achieving cost-effective protein expression, and rapid automated backbone assignment. The new methodology is applied for characterization of five cytosolic domains from T- and B-cell receptors in solution.
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| 22. |
- Isaksson, Linnéa
(författare)
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Intrinsically Disordered Domains of the B Cell Receptor Cell-Free Expression and Characterization by NMR
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After the last twenty years of research, the occurrence of flexible proteins without a fixed three-dimensional structure are no longer considered to be rare exceptions from the structure-function paradigm. Instead, intrinsically disordered proteins (IDPs) have become one of the most interesting subjects of modern protein research. NMR is the best and most suitable technique for investigating the details of this protein class, and cell-free protein synthesis (CFPS) offers several advantages compared to conventional in vivo synthesis for the production of IDPs. In this thesis, an integrated approach for efficient characterization of IDPs has been developed, combining CFPS and novel NMR methodology with fast spectroscopy and self-validating automatic assignment procedures. The technique has been demonstrated on disordered cytosolic domains of the B cell- and the T cell receptor. These domains are responsible for signal propagation into the immune cells, initiated by phosphorylation of tyrosines in their immunoreceptor tyrosine-based activation motifs (ITAMs). Secondary structure propensities have been observed and followed, going from a non-active form (non-phosphorylated) to an active form (phosphorylated) for the domains of the B cell receptor. A time-resolved technique for studying phosphorylation has also been developed and demonstrated on a B cell receptor domain. Isotopic enrichment of amino acids is often a prerequisite for studying proteins with NMR, also representing the major cost of the CFPS system. A way to efficiently incorporate these labeled amino acids has therefore been investigated in this work. CFPS does not only provide a unique technique for producing protease-sensitive IDPs, but also membrane proteins (MPs), inherently difficult to express in functional form. In this work it is demonstrated that CFPS can be successfully applied to express preparative amounts of co-solubilized MPs of varying size and complexities.
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| 23. |
- Isaksson, Linnéa, et al.
(författare)
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Signaling Mechanism of Phytochromes in Solution.
- 2021
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Ingår i: Structure. - : Elsevier BV. - 1878-4186 .- 0969-2126. ; 29:2, s. 151-160
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Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins guide the red/far-red photoresponse of plants, fungi, and bacteria. Crystal structures suggest that the mechanism of signal transduction from the chromophore to the output domains involves refolding of the so-called PHY tongue. It is currently not clear how the two other notable structural features of the phytochrome superfamily, the so-called helical spine and a knot in the peptide chain, are involved in photoconversion. Here, we present solution NMR data of the complete photosensory core module from Deinococcus radiodurans. Photoswitching between the resting and the active states induces changes in amide chemical shifts, residual dipolar couplings, and relaxation dynamics. All observables indicate a photoinduced structural change in the knot region and lower part of the helical spine. This implies that a conformational signal is transduced from the chromophore to the helical spine through the PAS and GAF domains. The discovered pathway underpins functional studies of plant phytochromes and may explain photosensing by phytochromes under biological conditions.
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| 24. |
- Kazimierczuk, Krzysztof, et al.
(författare)
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Resolution enhancement in NMR spectra by deconvolution with compressed sensing reconstruction
- 2020
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 56, s. 14585-14588
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Tidskriftsartikel (refereegranskat)abstract
- NMR spectroscopy is one of the basic tools for molecular structure elucidation. Unfortunately, the resolution of the spectra is often limited by inter-nuclear couplings. The existing workarounds often alleviate the problem by trading it for another deficiency, such as spectral artefacts or difficult sample preparation and, thus, are rarely used. We suggest an approach using the coupling deconvolution in the framework of compressed sensing (CS) spectra processing that leads to a major increase in resolution, sensitivity, and overall quality of NUS reconstruction. A new mathematical description of the decoupling by deconvolution explains the effects of thermal noise and reveals a relation with the underlying assumption of the CS. The gain in resolution and sensitivity for challenging molecular systems is demonstrated for the key HNCA experiment used for protein backbone assignment applied to two large proteins: intrinsically disordered 441-residue Tau and a 509-residue globular bacteriophytochrome fragment. The approach will be valuable in a multitude of chemistry applications, where NMR experiments are compromised by the homonuclear scalar coupling. This journal is
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| 25. |
- Kübel, Joachim, 1988, et al.
(författare)
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Transient IR spectroscopy identifies key interactions and unravels new intermediates in the photocycle of a bacterial phytochrome
- 2020
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Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 22:17, s. 9195-9203
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are photosensory proteins in plants, fungi, and bacteria, which detect red- and far-red light. They undergo a transition between the resting (Pr) and photoactivated (Pfr) states. In bacterial phytochromes, the Pr-to-Pfr transition is facilitated by two intermediate states, called Lumi-R and Meta-R. The molecular structures of the protein in these states are not known and the molecular mechanism of photoconversion is not understood. Here, we apply transient infrared absorption spectroscopy to study the photocycle of the wild-type and Y263F mutant of the phytochrome from Deinococcus radiodurans (DrBphP) from nano- to milliseconds. We identify two sequentially forming Lumi-R states which differ in the local structure surrounding the carbonyl group of the biliverdin D-ring. We also find that the tyrosine at position 263 alters local structure and dynamics around the D-ring and causes an increased rate of Pfr formation. The results shed new light on the mechanism of light-signalling in phytochrome proteins.
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| 26. |
- Körlof, Linnéa, et al.
(författare)
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Older Adults’ Experiences of Using Strategies to Maintain and Foster Social Participation: A Systematic Review with Metasynthesis of Qualitative Studies
- 2024
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Ingår i: Health & Social Care in the Community. - : Hindawi Publishing Corporation. - 0966-0410 .- 1365-2524.
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Forskningsöversikt (refereegranskat)abstract
- Social participation is positively associated with older adults’ health. Health-care services, therefore, need to empower older adults to adapt to the social changes that accompany aging. This systematic review, with a metasynthesis of qualitative studies, aimed to describe and develop an understanding of home-dwelling older adults’ (65 yrs+) experiences of using strategies to maintain and foster their social participation. The main search was performed in March 2022 using the PubMed, CINAHL, PsycINFO, and AMED databases and included peer-reviewed articles published between 2012 and 2022. A total of 35 full-text articles from 15 different countries were included and assessed for quality by the assessment tool for qualitative studies provided by the Critical Appraisal Skills Programme (CASP). The metasynthesis resulted in the main theme: strategically creating routines that foster social participation and two main categories: inward-looking strategies for social participation and outward-looking strategies for social participation. Each main category contained three subcategories. The findings suggest that for perceiving social participation, it is important for older adults to create routines with patterns of activities and to be able to engage in these activities. The findings further reflect that older adults use earlier experiences of social participation to facilitate the making of routines. This indicates that health-care interventions supporting older adults’ social participation must be applied early and with a health-promotive focus. Conclusively, researchers need to develop interventions that support older adults in healthy activity patterns by raising awareness of how to use inward-looking and outward-looking strategies to create routines for social participation. The findings further suggest that older adults’ possibilities for social participation could be supported by designing accessible venues that facilitate spontaneous meetings and encourage older adults’ own choices and initiatives for social participation.
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| 27. |
- La Fleur, Linnea, et al.
(författare)
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Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:7, s. 1741-1752
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.
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| 28. |
- La Fleur, Linnea, et al.
(författare)
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Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
- 2019
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Lundberg, Kristina, et al.
(författare)
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Strategisk miljöbedömning i långsiktig transportplanering
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Strategisk miljöbedömning (förkortat SMB) är en lagstadgad process som infördes i Miljöbalken 2004, som ett resultat av EU-direktivet (2001/42/EG) om bedömning av vissa planers och programs miljöpåverkan.Bestämmelserna gäller planer eller program som upprättas av myndigheter eller kommuner,till exempel översiktsplaner, havsplaner, avfallsplaner, transport- eller infrastrukturplaner. Syftet medSMB är att åstadkomma en integrering av hållbarhetsaspekter i ett tidigt, mer strategiskt skede avplaneringen där det finns möjligheter att göra olika strategiska val. I praktiken har det dock visat sig attSMB-processen används i alltför liten utsträckning och att genomförandet ofta är bristfällig. Detta harframkommit i forskning såväl som i utvärderingar av myndigheter.Forskningsprojektet TRAMP – Är långsiktig transportplanering och miljöbedömning kompatiblaprocesser? har under åren 2018–2020 analyserat och utvecklat stöd i utformningen av SMB iTrafikverkets långsiktiga transportinfrastrukturplanering, det vill säga inriktningsplanering ochåtgärdsplanering. I rapporten benämns dessa planeringssteg som nationell transportplanering.Även om resultat och rekommendationer är utformade för SMB i inriktnings- ochåtgärdsplanering är rapporten även relevant för andra aktörer som verkar i regional eller nationelltransportplanering såsom länsplaneupprättare, regeringskansliet och andra statliga myndigheter.Projektet fokuserar på såväl SMB:s roll i den nationella transportplaneringen som kompatibilitetenmellan dels Trafikverkets planeringspraktik, dels den lagstiftning och metodpraxis som finns gällandeSMB. Studien baseras på en utvärdering och analys av de två senaste planeringsomgångarna (2014–2025 och 2018–2029) med fokus på den genomförda SMB-processen. De metoder som använts istudien har varit dokumentstudier, workshops och intervjuer. Workshops och intervjuer har genomförtsmed experter, planerare och chefer på Trafikverket, men även med tjänstepersoner på andranationella myndigheter samt departement och politiker som har varit centralt involverade i, eller avandra skäl har god insyn i, den nationella transportplaneringen under de två senaste planeringsomgångarna(2014–2025 samt 2018–2029).Utifrån resultaten har förslag tagits fram till hur SMB kan utvecklas till en process som ger nytta ochfrämjar en hållbar utveckling.
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| 33. |
- Markeviciute, Vetra, et al.
(författare)
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Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation : A regenerative medicine approach to improve fracture fixation
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Ingår i: Acta Biomaterialia. - 1742-7061.
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Tidskriftsartikel (refereegranskat)abstract
- Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats. Using systemic ZA administration at 2-weeks post-surgery, we demonstrated that the implant surrounded by HA particles showed significantly higher peri‑implant bone formation compared to the unaugmented implants at 6-weeks. We then evaluated the optimal timing (day 1, 3, 7 and 14) of ZA administration to achieve a robust effect on peri‑implant bone formation. Using fluorescent ZA, we demonstrated that the uptake of ZA in the CaS/HA material was the highest at 3- and 7-days post-implantation and the uptake kinetics had a profound effect on the eventual peri‑implant bone formation. We furthered our concept in a feasibility study on trochanteric fracture patients randomized to either CaS/HA augmentation or no augmentation followed by systemic ZA treatment. Radiographically, the CaS/HA group showed signs of increased peri‑implant bone formation compared with the controls. Finally, apart from HA, we demonstrated that the concept of biologically activating a ceramic material by ZA could also be applied to β-tricalcium phosphate. This novel approach for fracture treatment that enhances immediate and long-term fracture fixation in osteoporotic bone could potentially reduce reoperations, morbidity and mortality. Statement of significance: • Fracture fixation in an ageing population is challenging. Biomaterial-based augmentation of fracture fixation devices has been attempted but lack of satisfactory biological response limits their widespread use. • We report the biological activation of locally implanted microparticulate hydroxyapatite (HA) particles placed around an implant by systemic administration of the bisphosphonate zoledronic acid (ZA). The biological activation of HA by ZA enhances peri‑implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri‑implant bone formation. • We translate the developed concept from small animal models of implant integration to a proof-of-concept clinical study on osteoporotic trochanteric fracture patients. • ZA based biological activation can also be applied to other calcium phosphate biomaterials.
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| 34. |
- Mayzel, Maxim, et al.
(författare)
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Time-resolved multidimensional NMR with non-uniform sampling
- 2014
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Ingår i: Journal of Biomolecular Nmr. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 58:2, s. 129-139
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved experiments demand high resolution both in spectral dimensions and in time of the studied kinetic process. The latter requirement traditionally prohibits applications of the multidimensional experiments, which, although capable of providing invaluable information about structure and dynamics and almost unlimited spectral resolution, require too lengthy data collection. Our work shows that the problem has a solution in using modern methods of NMR data collection and signal processing. A continuous fast pulsing three-dimensional experiment is acquired using non-uniform sampling during full time of the studied reaction. High sensitivity and time-resolution of a few minutes is achieved by simultaneous processing of the full data set with the multi-dimensional decomposition. The method is verified and illustrated in realistic simulations and by measuring deuterium exchange rates of amide protons in ubiquitin. We applied the method for characterizing kinetics of in vitro phosphorylation of two tyrosine residues in an intrinsically disordered cytosolic domain of the B cell receptor protein CD79b. Signals of many residues including tyrosines in both phosphorylated and unmodified forms of CD79b are found in a heavily crowded region of 2D H-1-N-15 correlation spectrum and the significantly enhanced spectral resolution provided by the 3D time-resolved approach was essential for the quantitative site-specific analysis.
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| 35. |
- Mboya, Innocent B, et al.
(författare)
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Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults
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Ingår i: Annals of Epidemiology. - 1047-2797. ; 97, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths.METHODS: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17-39 years at baseline in 1963-2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975-1985, ≥1985 and women: <1985, 1985-1994, ≥1995).RESULTS: Comparing men with obesity vs. normal weight, all-cause and "other-cause" mortality associations decreased over periods; HR (95% CI) 1.92 (1.83-2.01) and 1.70 (1.58-1.82) for all-cause and 1.72 (1.58-1.87) and 1.40 (1.28-1.53) for "other-cause" mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51-2.94) and 3.91 (3.37-4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women.CONCLUSIONS: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.
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| 36. |
- Mboya, Innocent B, et al.
(författare)
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Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults
- 2024
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Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 97, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths.Methods: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17–39 years at baseline in 1963–2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975–1985, ≥1985 and women: <1985, 1985–1994, ≥1995).Results: Comparing men with obesity vs. normal weight, all-cause and “other-cause” mortality associations decreased over periods; HR (95% CI) 1.92 (1.83–2.01) and 1.70 (1.58–1.82) for all-cause and 1.72 (1.58–1.87) and 1.40 (1.28–1.53) for “other-cause” mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51–2.94) and 3.91 (3.37–4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women.Conclusions: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.
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| 37. |
- Pierantoni, Maria, et al.
(författare)
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Heterotopic mineral deposits in intact rat Achilles tendons are characterized by a unique fiber-like structure
- 2023
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Ingår i: Journal of Structural Biology: X. - : Elsevier BV. - 2590-1524. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Heterotopic mineralization entails pathological mineral formation inside soft tissues. In human tendons mineralization is often associated with tendinopathies, tendon weakness and pain. In Achilles tendons, mineralization is considered to occur through heterotopic ossification (HO) primarily in response to tendon pathologies. However, refined details regarding HO deposition and microstructure are unknown. In this study, we characterize HO in intact rat Achilles tendons through high-resolution phase contrast enhanced synchrotron X-ray tomography. Furthermore, we test the potential of studying local tissue injury by needling intact Achilles tendons and the relation between tissue microdamage and HO. The results show that HO occurs in all intact Achilles tendons at 16 weeks of age. HO deposits are characterized by an elongated ellipsoidal shape and by a fiber-like internal structure which suggests that some collagen fibers have mineralized. The data indicates that deposition along fibers initiates in the pericellular area, and propagates into the intercellular area. Within HO deposits cells are larger and more rounded compared to tenocytes between unmineralized fibers, which are fewer and elongated. The results also indicate that multiple HO deposits may merge into bigger structures with time by accession along unmineralized fibers. Furthermore, the presence of unmineralized regions within the deposits may indicate that HOs are not only growing, but mineral resorption may also occur. Additionally, phase contrast synchrotron X-ray tomography allowed to distinguish microdamage at the fiber level in response to needling. The needle injury protocol could in the future enable to elucidate the relation between local inflammation, microdamage, and HO deposition.
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| 38. |
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| 39. |
- Rosenlöw, Joakim, et al.
(författare)
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Tyrosine Phosphorylation within the Intrinsically Disordered Cytosolic Domains of the B-Cell Receptor: An NMR-Based Structural Analysis
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Intrinsically disordered proteins are found extensively in cell signaling pathways where they often are targets of posttranslational modifications e. g. phosphorylation. Such modifications can sometimes induce or disrupt secondary structure elements present in the modified protein. CD79a and CD79b are membrane-spanning, signal-transducing components of the B-cell receptor. The cytosolic domains of these proteins are intrinsically disordered and each has an immunoreceptor tyrosine-based activation motif (ITAM). When an antigen binds to the receptor, conserved tyrosines located in the ITAMs are phosphorylated which initiate further downstream signaling. Here we use NMR spectroscopy to examine the secondary structure propensity of the cytosolic domains of CD79a and CD79b in vitro before and after phosphorylation. The phosphorylation patterns are identified through analysis of changes of backbone chemical shifts found for the affected tyrosines and neighboring residues. The number of the phosphorylated sites is confirmed by mass spectrometry. The secondary structure propensities are calculated using the method of intrinsic referencing, where the reference random coil chemical shifts are measured for the same protein under denaturing conditions. Our analysis revealed that CD79a and CD79b both have an overall propensity for alpha-helical structure that is greatest in the C-terminal region of the ITAM. Phosphorylation of CD79a caused a decrease in helical propensity in the C-terminal ITAM region. For CD79b, the opposite was observed and phosphorylation resulted in an increase of helical propensity in the C-terminal part.
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| 40. |
- Salomonsson, Annette, et al.
(författare)
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Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer
- 2020
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Ingår i: Cancer Medicine. - : Blackwell Publishing Ltd. - 2045-7634. ; 9:15, s. 5609-5619
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Tidskriftsartikel (refereegranskat)abstract
- Aims High expression of the RNA-binding motif protein 3 (RBM3) correlates with improved prognosis in several major types of cancer. The aim of the present study was to examine the prognostic value of RBM3 protein and mRNA expression in non-small cell lung cancer (NSCLC).Methods and results Immunohistochemical expression of RBM3 was evaluated in surgically treated NSCLC from two independent patient populations (n = 213 and n = 306). Staining patterns were correlated with clinicopathological parameters, overall survival (OS), and recurrence-free interval (RFI). Cases with high nuclear RBM3 protein expression had a prolonged 5-year OS in both cohorts when analyzing adenocarcinomas separately (P = .02 and P = .01). RBM3 remained an independent prognostic factor for OS in multivariable analysis of cohort I (HR 0.44, 95% CI 0.21-0.90) and for RFI in cohort II (HR 0.38, 95% CI 0.22-0.74). In squamous cell carcinoma, there was instead an insignificant association to poor prognosis. Also, the expression levels of RBM3 mRNA were investigated in 2087 lung adenocarcinomas and 899 squamous cell carcinomas assembled from 13 and 8 public gene expression microarray datasets, respectively. The RBM3 mRNA levels were not clearly associated with patient outcome in either adenocarcinomas or squamous cell carcinomas.Conclusions The results from this study support that high protein expression of RBM3 is linked to improved outcome in lung adenocarcinoma.
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