| 1. |
- Franceschini, N., et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 2. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
- Andreoni, I., et al.
(author)
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Follow Up of GW170817 and Its Electromagnetic Counterpart by Australian-Led Observing Programmes
- 2017
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In: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
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Research review (peer-reviewed)abstract
- The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (similar to 2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
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| 4. |
- Franceschini, N, et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
-
Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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| 5. |
- Parker, C., et al.
(author)
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Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
- 2013
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:3, s. 213-223
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Journal article (peer-reviewed)abstract
- Background Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. Methods In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. Results At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. Conclusions In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Thunes, KH, et al.
(author)
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The arthropod community of Scots pine (Pinus sylvestris L.) canopies in Norway
- 2004
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In: Entomologica Fennica. - 0785-8760. ; 15:2, s. 65-90
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Research review (peer-reviewed)abstract
- We summarise the findings of arthropods collected by fogging the canopy of 24 pine trees in two sites in Eastern and Western Norway. From the samples, taken in 1998 and in 1999, almost 30,000 specimens were determined to 512 species, with Diptera being most species rich (210 species), followed by Coleoptera (76 species) and Araneae (49 species). Of the 96 new species records, nine were new to science (5 Diptera and 4 Oribatida), two were new to the European, three to the Scandinavian and 82 to the Norwegian faunas. The paper demonstrates the need for detailed faunistical inventories of European forests.
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| 10. |
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| 11. |
- Berkelmans, G. F. N., et al.
(author)
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Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice
- 2022
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In: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 145, s. 70-80
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Journal article (peer-reviewed)abstract
- Objectives: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting.& nbsp;Study design and setting: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ? diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naive approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.& nbsp;Results: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).& nbsp;Conclusion: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing. (C)& nbsp;2022 Elsevier Inc. All rights reserved.
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| 12. |
- Bhat, N. D. R., et al.
(author)
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Observations of Low-frequency Radio Emission from Millisecond Pulsars and Multipath Propagation in the Interstellar Medium
- 2018
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In: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 238:1
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Journal article (peer-reviewed)abstract
- Studying the gravitational-wave sky with pulsar timing arrays (PTAs) is a key science goal for the Square Kilometre Array (SKA) and its pathfinder telescopes. With current PTAs reaching sub-microsecond timing precision, making accurate measurements of interstellar propagation effects and mitigating them effectively has become increasingly important to realize PTA goals. As these effects are much stronger at longer wavelengths, low-frequency observations are most appealing for characterizing the interstellar medium (ISM) along the sight lines toward PTA pulsars. The Murchison Widefield Array (MWA) and the Engineering Development Array (EDA), which utilizes MWA technologies, present promising opportunities for undertaking such studies, particularly for PTA pulsars located in the southern sky. Such pulsars are also the prime targets for PTA efforts planned with the South African MeerKAT, and eventually with the SKA. In this paper we report on observations of two bright southern millisecond pulsars, PSR J0437-4715 and PSR J2145-0750, made with these facilities; MWA observations sampled multiple frequencies across the 80-250 MHz frequency range, while the EDA provided direct-sampled baseband data to yield a large instantaneous usable bandwidth of similar to 200 MHz. Using these exploratory observations, we investigate various aspects relating to pulsar emission and ISM properties, such as spectral evolution of the mean pulse shape, scintillation as a function of frequency, chromaticity in interstellar dispersion, and flux density spectra at low frequencies. Systematic and regular monitoring observations will help ascertain the role of low-frequency measurements in PTA experiments, while simultaneously providing a detailed characterization of the ISM toward the pulsars, which will be useful in devising optimal observing strategies for future PTA experiments.
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| 13. |
- Broderick, J. W., et al.
(author)
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LOFAR 144-MHz follow-up observations of GW170817
- 2020
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 494:4, s. 5110-5117
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Journal article (peer-reviewed)abstract
- We present low-radio-frequency follow-up observations of AT 2017gfo, the electromagnetic counterpart of GW170817, which was the first binary neutron star merger to be detected by Advanced LIGO-Virgo. These data, with a central frequency of 144 MHz, were obtained with LOFAR, the Low-Frequency Array. The maximum elevation of the target is just 13 degrees.7 when observed with LOFAR, making our observations particularly challenging to calibrate and significantly limiting the achievable sensitivity. On time-scales of 130-138 and 371-374 d after the merger event, we obtain 3s upper limits for the afterglow component of 6.6 and 19.5mJy beam(-1), respectively. Using our best upper limit and previously published, contemporaneous higher frequency radio data, we place a limit on any potential steepening of the radio spectrum between 610 and 144 MHz: the two-point spectral index alpha(610)(144) greater than or similar to -2.5. We also show that LOFAR can detect the afterglows of future binary neutron star merger events occurring at more favourable elevations.
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| 14. |
- Jones, Gregory T., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Journal article (peer-reviewed)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 15. |
- McGurnaghan, S. J., et al.
(author)
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Development and validation of a cardiovascular risk prediction model in type 1 diabetes
- 2021
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2001-2011
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Journal article (peer-reviewed)abstract
- Aims/hypothesis We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. Methods A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., >= 10%) using the model with the percentage eligible for statins using current guidelines by age. Results The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer- Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic foam 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and >= 60 years, respectively (alp values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those >= 40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >= 10% in 10 years. Conclusions/interpretation A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention. the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.
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| 16. |
- Webb, Thomas R., et al.
(author)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Journal article (peer-reviewed)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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| 17. |
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| 18. |
- Mustamäki, N, et al.
(author)
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Faktablad från integrerad kustfiskövervakning 2020:1 – Fjällbacka, Västerhavet, 1989–2019; Torhamn, södra Egentliga Östersjön, 2002–2019; Kvädöfjärden, Egentliga Östersjön, 1981–2019; Holmöarna, Bottniska viken, 1989–2019.
- 2020
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Reports (other academic/artistic)abstract
- Inom den nationella miljöövervakningen av kust och hav bedrivs årligen sedan slutet av 1980-talet ett program för integrerad kustfiskövervakning i fyra nationella referensområden, ett vardera i Bottniska viken, Egentliga Östersjön, södra Egentliga Östersjön och Västerhavet. Syftet med programmet är att kartlägga fiskbeståndens status samt fiskens hälsotillstånd och miljögiftsbelastning för att upptäcka förändringar som indikerar storskalig påverkan av miljöhot som eutrofiering, miljögifter, klimatförändringar och andra miljöfaktorer. Detta faktablad sammanfattar resultaten från den integrerade kustfiskövervakningen i alla fyra områden under tidsperioden 1980–2019. Temperatur, siktdjup och salthalt: Miljöförhållandena, kvantifierat som siktdjup, vattentemperatur och salthalt, i provfiskeområdena har varit relativt stabila sedan början av 2000-talet. Salthalten är naturligt högst i Fjällbacka i Västerhavet och lägst i Holmöarna i Bottniska viken. Längre tidsserier med början under 1960-talet i Kvädöfjärden visar på en ökad övergödning (minskat siktdjup) och en ökad vattentemperatur i området. Dessa förändringar avspeglar både den ökande övergödningen och pågående klimatförändringen i Östersjön. Fisksamhällets struktur och funktion: Fisksamhället i provfiskeområdena påverkas av de lokala miljöbetingelserna och är mer artrikt och diverst i de marina förhållandena i Fjällbacka på Västkusten jämfört med de mer sötvattenspåverkade områdena i Östersjön. I Fjällbacka var provfiskefångsterna av torsk och ål relativt höga under 2019, och ål är även en art för vilken provfiskefångsterna ökat under senare år. I Östersjön finns en generell trend för de tre provfiskeområdena där fångsterna av karpfiskar (framförallt mört) som gynnas av varmare och mer näringsrika vatten har varit höga eller ökande sedan början av 2000-talet. I Holmöarna har även fångsterna av sik ökat och i Torhamn har rovfisken gädda minskat under samma tidsperiod. Abborren är en indikatorart för kustfisksamhällets tillstånd, och det finns en tendens till minskande provfiskefångster av abborre sedan början av 2000-talet i alla områden i Östersjön. De fångade abborrarnas storlek har dock inte ändrats under den studerade tidsperioden. Tillväxt hos abborre och tånglake: Abborrens och tånglakens längd vid ålder har generellt ökat i alla provfiskeområden, vilket indikerar snabbare tillväxt hos fisken. Reproduktion hos tånglake: Det finns inga tydliga tecken på förändring i tånglakens reproduktion sedan början av 2000-talet, även om förekomsten av onormala yngel observerats i alla provfiskeområden och andelen av dessa under enstaka år överskrider det föreslagna gränsvärdet för den naturliga bakgrundsnivån. En oroväckande trend är dock en successiv maskulinisering av tånglakeynglen i Fjällbacka och Kvädöfjärden, där proportionen av honyngel minskat sedan början av 2000-talet. Hälsotillstånd hos abborre och tånglake: Abborrens och tånglakens hälsotillstånd är negativt påverkade i de undersökta kustområdena. Det finns dock tecken på att den negativa utvecklingen har planat ut något under de senaste åren. Den tidigare tidstrenden med minskningen av relativ gonadvikt hos abborrhonor (GSI) har avstannat, men GSI under de senaste åren är fortfarande ca 30 % lägre än i början av tidsperioden. GSI kan påverkas av att fiskens tillväxt ökat, av flera olika miljöfaktorer, samt även av exponering för miljögifter som påverkar könsmognaden och fortplantningen. Den tidigare ökningen i aktiviteten av avgiftningsenzymet EROD hos abborre har avstannat, men aktiviteten under senare år ligger fortfarande på en högre nivå än i början av tidsperioden. Detta tyder på att fisken periodvis är exponerad för organiska miljögifter, t.ex. PAHer eller ämnen med dioxinlik effekt. Starkt ökade aktiviteter av leverenzymerna GR och katalas indikerar även att det föreligger en ökad oxidativ stress hos abborre och tånglake av båda könen. Dessutom observeras hos abborren och tånglaken tecken på påverkat immunförsvar, påverkad saltreglering och ämnesomsättning. Metaller och organiska miljögifter i abborre och tånglake: Flertalet metaller, pesticider och PCB:er visar inga tydliga trender från början av 2000-talet hos varken abborre eller tånglake, men det finns en del undantag. Kvicksilver ökar i abborre men minskar i tånglake. Sett över hela mätserien, från 1980, så minskade halterna av kvicksilver i abborre fram till slutet av 1990-talet för att därefter öka igen. Halterna ligger över EU:s gränsvärde för kvicksilver i toppredatorer, men under gränsvärdet för skydd av människans hälsa vid konsumtion av fiskeriprodukter. Hos abborre ses en indikation på minskande blyhalter i alla provfiskeområden och halterna ligger under EU:s gränsvärde. Halterna av koppar ökar i både abborre och tånglake i Kvädöfjärden. Pesticiden HCB ökar i abborre i Holmöarna och en ökning indikeras även i Kvädöfjärden. Liksom för kvicksilver, har halterna av HCB minskat från tidsseriens början (mitten av 1980-talet) fram till början av 2000-talet, för att därefter öka igen. Halterna ligger under EU:s gränsvärde. Pesticiderna DDE och α-HCH visar inga förändringar. För PCB ses inga tydliga trender men en indikation på minskning ses i abborre i Holmöarna för PCB-118 och PCB-153. Halterna av PCB-153 är under gränsvärdet medan halterna av PCB-118 ligger över gränsvärdet i tånglake i Fjällbacka. Sammanvägd bedömning av tillståndet för kustfisk i referensområdena: Utvecklingen av de studerade fisksamhällena visar en tydlig påverkan från övergödning och klimatförändring, och de ökande fångsterna av karpfisk i områdena i Östersjön indikerar en icke önskvärd utveckling ur ett ekosystemperspektiv. Det finns även positiva signaler i att fångsterna av ål i Fjällbacka, gös i Kvädöfjärden och sik i Holmöarna ökar. Oroväckande för ekosystemets struktur och funktion, samt dess förmåga att bidra med viktiga ekosystemtjänster är de vikande fångsterna av gädda i Torhamn och tendensen till minskade fångster av nyckelarten abborre i alla områden. Vad dessa förändringar grundar sig i är inte klarlagt, men ökad predation från säl, skarv och storspigg är faktorer som kan bidra till det observerade tillståndet. Att abborrens storlek och tillväxt samtidigt ökar tyder på goda förutsättningar för artens populationsutveckling, och indikerar samtidigt att fisketrycket i de undersökta områdena inte är förhöjt. Det kan heller inte uteslutas att den ökade tillväxten hos abborre kan vara kopplad till en minskad inomartskonkurrens då det finns en indikation att förekomsten av abborre minskar i alla områden. Den minskande förekomsten av abborre kan möjligen även kopplas till att fiskens hälsostatus inte är tillfredställande i provfiskeområdena. Ett flertal hälsovariabler uppvisar förändringar och en tydlig påverkan på fiskens hälsa. Utöver inducerat avgiftningssystem och förminskade gonader (bara hos abborre), observeras ökad oxidativ stress, påverkat immunförsvar samtpåverkad saltreglering och ämnesomsättning. Förändringarna visar att flera viktiga fysiologiska funktioner hos fisken är påverkade och det kan inte uteslutas att orsaken kan vara att fisken är exponerad för kemiska ämnen. Vilka ämnen detta är och hur det observerade hälsotillståndet för fisken kopplar till andra miljöförändringar är inte klarlagt, då halterna av de flesta av de undersökta miljögifterna minskar eller är oförändrade över tid. Ökande halter ses dock av kvicksilver och pesticiden HCB i abborre sedan 2002, men inte i tånglake. Detta skulle kunna tyda på förändringar i födoväven och i arternas födoval. Halterna av koppar ökar i abborre både från Holmöarna och Kvädöfjärden och i tånglake från Kvädöfjärden. Detta skulle kunna bero på den ökade användningen av båtbottenfärger innehållandes koppar under de senaste 10 åren, men andra förklaringar är också möjliga. Den pågående maskuliniseringen av tånglakeynglen i Fjällbacka och den periodvis höga andelen av onormala yngel är ytterligare en indikation på att tillståndet i våra kustfisksamhällen inte är tillfredställande. Orsaken bakom detta är inte klarlagt.Det är oroande att de observerade förändringarna sker i referensområden som anses vara relativt opåverkade av direkt mänsklig aktivitet. Det är därför angeläget att klarlägga om det är okända miljögifter, kända miljögifter som inte övervakas idag, utöver andra bakomliggande miljöfaktorer såsom övergödning, klimatförändringar och förändrad födovävsstruktur som orsakar förändringarna i kustfiskens hälsotillstånd och förändringarna som ses på populationsnivå hos abborre, rovfisk och karpfisk.
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| 19. |
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| 20. |
- Nilsson, S., et al.
(author)
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A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer
- 2012
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In: European Journal of Cancer. - Oxford : Elsevier. - 0959-8049 .- 1879-0852. ; 48:5, s. 678-686
-
Research review (peer-reviewed)abstract
- Purpose: To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical. Methods: One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 kBq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders. Results: A significant dose response for pain index was seen at week 2 (P = .035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 kBq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P = .008, P = .0005, P = .002, and P < .0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P = .04, .01, .002 and .02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P = .0067). All doses were safe and well tolerated. Conclusion: Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed. (C) 2012 Elsevier Ltd. All rights reserved.
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| 21. |
- Shimwell, T. W., et al.
(author)
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The LOFAR Two-metre Sky Survey: V. Second data release
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
-
Journal article (peer-reviewed)abstract
- In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120a 168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44 30a and 1h00m +28 00a and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6a resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beama 1; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2a; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beama 1. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > a ±a 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20a resolution 120a168 MHz continuum images have a median rms sensitivity of 95 μJy beama 1, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480a A a 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beama 1 at 4a and 2.2 mJy beama 1 at 20a; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data to facilitate the thorough scientific exploitation of this unique dataset.
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| 22. |
- Taimour, S., et al.
(author)
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Survival, cardiovascular morbidity, and reinterventions after elective endovascular aortic aneurysm repair in patients with and without diabetes: A nationwide propensity-adjusted analysis
- 2019
-
In: Vascular Medicine. - : SAGE Publications. - 1358-863X .- 1477-0377. ; 24:6, s. 539-546
-
Journal article (peer-reviewed)abstract
- Epidemiological data indicate decreased risk for development and growth of abdominal aortic aneurysm (AAA) among patients with diabetes mellitus (DM). On the other hand, DM adds to increased cardiovascular (CV) morbidity and mortality. In a nationwide observational cohort study of patients registered in the Swedish Vascular Register and the Swedish National Diabetes Register, we evaluated potential effects of DM on total mortality, CV morbidity, and the need for reintervention after elective endovascular aneurysm repair (EVAR) for AAA. We compared 748 patients with and 2630 without DM with propensity score-adjusted analysis, during a median 4.22 years of follow-up for patients with DM, and 4.05 years for those without. In adjusted analysis, diabetic patients showed higher rates of acute myocardial infarction (AMI) during follow-up (relative risk (RR) 1.44, 95% CI 1.06-1.95; p = 0.02), but lower need for reintervention (RR 0.12, CI 0.02-0.91; p = 0.04). There were no differences in total (RR 0.88, CI 0.74-1.05; p = 0.15) or CV (RR 1.58, CI 0.87-2.86; p = 0.13) mortality, or stroke (RR 0.95, CI 0.68-1.32; p = 0.75) during follow-up. In conclusion, patients with DM had higher rates of AMI and lower need for reintervention after elective EVAR than those without DM, whereas neither total nor CV mortality differed between groups. The putative protective effects of DM towards further AAA enlargement and late sac rupture may help explain the lower need for reintervention and absence of excess mortality.
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| 23. |
- Wang, YQ, et al.
(author)
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A cell fitness selection model for neuronal survival during development
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4137-
-
Journal article (peer-reviewed)abstract
- Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.
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| 24. |
- Wang, YQ, et al.
(author)
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Muscle-selective RUNX3 dependence of sensorimotor circuit development
- 2019
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In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 146:20
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Journal article (peer-reviewed)abstract
- The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet, the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 controls also the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin-3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator critical for specifying a generic PSN type identity after neurogenesis, is later regulated by target muscle-derived signal to contribute to the specialized aspects of the sensorimotor connection selectivity.
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| 25. |
- Adamsson Eryd, Samuel, et al.
(author)
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Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study
- 2016
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In: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 354
-
Journal article (peer-reviewed)abstract
- OBJECTIVES To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.
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| 26. |
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| 27. |
- Alaiya, A, et al.
(author)
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Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma
- 2000
-
In: Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology. - : Hindawi Limited. - 0921-8912. ; 21:1, s. 1-9
-
Journal article (peer-reviewed)abstract
- Cells were collected from prostate hyperplasias (n=6) and prostate carcinomas (n=6) and subjected to two‐dimensional gel electrophoresis (2‐DE). The resulting polypeptide patterns were analysed with the PDQUEST computer software. Malignant tumors showed significant increases in the level of expression of proliferating cell nuclear antigen (PCNA), calreticulin, HSP 90 and pHSP 60, oncoprotein 18(v), elongation factor 2, glutathione‐S‐transferaseπ(GST‐π), superoxide dismutase and triose phosphate isomerase. In addition, decreases in the levels of tropomyosin‐1 and 2 and cytokeratin 18 were observed in prostate carcinomas compared to prostate hyperplasias. This pattern of alterations is similar to that observed in other carcinomas in our previous studies. All malignant tumors showed simultaneous alterations in 5 or more of 9 markers studied, whereas only one case of benign hyperplasia showed alterations in 5 markers. The EST‐data base for prostate tumors available from NCI (CGAP) was searched for the expression of the mRNAs corresponding to proteins identified in our gels. Large differences in the relative expression of mRNAs and proteins were observed. Our data show alterations in the pattern of polypeptide expression in prostate carcinomas which are similar to those observed in other carcinomas.
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| 28. |
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| 29. |
- Askling, J., et al.
(author)
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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
- 2016
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
-
Journal article (peer-reviewed)abstract
- Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Cole, S. G., et al.
(author)
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Arctic games : An analytical framework for identifying options for sustainable natural resource governance
- 2016
-
In: The Polar Journal. - : Taylor and Francis Ltd.. - 2154-896X .- 2154-8978. ; 6:1
-
Journal article (peer-reviewed)abstract
- Changes in the Arctic are fuelled by a variety of drivers, including global warming, economic growth, improved access to natural resources, technological advances and globalisation processes. Further, the region is characterised by a diverse set of international agreements, national legislations and common pool resources. This presents challenges for actors to suggest, evaluate and agree on sustainable development alternatives. We propose an analytical framework to better understand (1) the types of trade-offs associated with Arctic futures and (2) actors’ incentives for strategic behaviour. In the framework, game theory illuminates incentives and strategies among actors, cost-benefit analysis and economic valuation of ecosystem services help identify socially desirable outcomes and institutional analysis provides insight on how governance structures can support or interfere with policy intervention. We apply the proposed framework by analysing possible oil development futures for Lofoten in Northern Norway. For example, institutional analysis and estimates of costs and benefits of reducing oil spill risk and their distribution among actors are used for discussing incentive structures, including the use of side payments as a mechanism to mitigate conflicting interests.
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| 38. |
- De Palma, Adriana, et al.
(author)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
-
Journal article (peer-reviewed)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 39. |
- Ericson, Y, et al.
(author)
-
Faktablad från Integrerad kustfiskövervakning: Fjällbacka (Västerhavet) 1989-2015
- 2016
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In: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:1
-
Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Fjällbacka-området 1989-2015. Övervakningen visar att situationen för tånglake i Fjällbacka är ansträngd. En återhämtning kan dock skönjas de allra sista åren. Tidigare vikande fångster och en försämring av tånglakens hälsotillstånd samt yngelstatus antyder att arten påverkas negativt av omgivningsfaktorer såsom den ökande vattentemperaturen, syrenivåer och exponering för kemikalier.
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| 40. |
- Ericson, Y, et al.
(author)
-
Faktablad från Integrerad kustfiskövervakning: Holmön (Bottniska viken) 1989-2015.
- 2016
-
In: Faktablad 2016 från Inst för Akvatiska Resurser, SLU. ; :2016: 2
-
Journal article (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen vid Holmön under tidsperioden 1989-2015. Övervakningen visar för varje år ett alltmer påverkat hälsotillstånd hos abborre trots att de flesta analyserade metaller och organiska miljögifter visar nedåtgående trender eller oförändrade halter. Den tydliga och successiva påverkan som ses på hälsotillståndet på individnivå har ännu inte resulterat i några påtagliga förändringar på bestånds- och samhällsnivå.
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| 41. |
- Ericson, Y, et al.
(author)
-
Faktablad från Integrerad kustfiskövervakning: Kvädöfjärden (Egentliga Östersjön) 1989-2015.
- 2016
-
In: Faktablad 2016 från Inst för Akvatiska Resurser, SLU. ; :2016:3
-
Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Kvädöfjärden under tidsperioden 1989-2015. Kustfiskövervakningen visar på minskande karpfiskbestånd, minskad totalfångst av fisk och ett påverkat hälsotillstånd hos abborre och tånglake, samtidigt som de flesta analyserade miljögifter visar nedåtgående trender eller oförändrade halter.
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| 42. |
- Ericson, Y, et al.
(author)
-
Faktablad från Integrerad kustfiskövervakning: Torhamn (södra Egentliga Östersjön) 2002-2015
- 2016
-
In: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:4
-
Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Torhamnsområdet under tidsperioden 2002-2015. Resultaten från tretton års undersökningar visar en alltmer tydlig påverkan på hälsotillståndet hos abborre liknande den som observeras hos abborre och tånglake i andra kustreferensområden. Denna tydliga och successiva påverkan som ses på abborrens hälsa på individnivå har ännu inte resulterat i några påtagliga förändringar på bestånds- eller samhällsnivå.
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| 43. |
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| 44. |
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| 46. |
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| 47. |
- Franzén, Lovisa, et al.
(author)
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Spatially resolved transcriptomics of human and mouse fibrotic lung
- 2022
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60
-
Journal article (other academic/artistic)abstract
- Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive and irreversible scarring of the lung tissue. Development of new efficacious and safe treatments is hampered by limited understanding of disease pathogenesis, lack of predictive preclinical models, and narrow therapeutic index of candidate drugs targeting complex biologies. Here, we tackle these aspects by generating spatially resolved transcriptomic maps of fibrotic lungs from clinical samples and a preclinical mouse model. We utilized the Visium platform to study parenchyma biopsies from four healthy lungs and regions of varying fibrotic severity from four IPF patient lungs. By mapping single cell RNA-seq data spatially, we were able to detect distinct fibroblast populations in different regions of the lesioned IPF lung, as well as the presence of various immune cell populations. To study lung fibrosis preclinically in vivo, the bleomycin mouse model is the most widely used alternative, although its translatability to human disease is disputed. Visium data from mouse lungs collected at two time points following bleomycin administration were generated, which allowed us to characterize the fibrotic lesions and inflammatory areas in their spatiotemporal context. In addition, mass spectrometry imaging was performed on adjacent tissue sections to provide paired spatial metabolomics. Herein, we have generated spatial maps of the lung fibrosis transcriptome from IPF lung biopsies and bleomycin-injured mouse lungs, providing an extensive resource to probe disease pathogenesis and animal model translatability.
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| 48. |
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| 49. |
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| 50. |
- Lange, S, et al.
(author)
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The kinase domain of titin controls muscle gene expression and protein turnover
- 2005
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5728, s. 1599-1603
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Journal article (peer-reviewed)abstract
- The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.
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