| 1. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 2. |
- Wernroth, Lisa, et al.
(författare)
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Development of gut microbiota during the first 2 years of life
- 2022
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
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| 3. |
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| 4. |
- Baldanzi, Gabriel, et al.
(författare)
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Evening chronotype is associated with elevated biomarkers of cardiometabolic risk in the EpiHealth cohort: a cross-sectional study
- 2022
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population- based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. Methods: In 2,471 participants (49.7% men, mean age 61.2±8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self- reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. Results: We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. Conclusions: In this population-based study, proteins previously related with cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders.
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| 5. |
- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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| 6. |
- Larsson, Jenny, et al.
(författare)
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Farm characteristics and management routines related to neonatal porcine diarrhoea: a survey among Swedish piglet producers
- 2016
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: In recent years reports from a number of countries, including Sweden, describe problems with diarrhoea in newborn piglets despite the use of previously effective preventive measures. This seemingly altered disease pattern of neonatal porcine diarrhoea (NPD) warrants investigations on the magnitude and manifestation of the problem. The aim of the present study was to investigate the herd-level prevalence of NPD in Sweden and to describe disease characteristics and intervention strategies used in affected herds. To obtain this information a questionnaire was developed and sent out to 170 randomly selected herds. The presence of NPD in the herds was specified as "Yes", "No" or "Occasional cases" during the preceding year.Results: A response rate of 58% (98/170) was achieved. The total prevalence of farmer experienced NPD, including occasional cases was 79.6% (95% CI 70.6-86.4%). Most herds (85%; 83/98) employed maternal vaccination against enterotoxigenic Escherichia coli (ETEC). The most common treatment regimens used in affected herds included antimicrobials only (43%; 18/42) or antimicrobials in combination with supplementary fluids (33%; 14/42). Trimethoprim in combination with a sulphonamide was the drug of choice in 57% (24/42) of the affected herds whereas the remaining herds used a broad range of other antimicrobials (neomycin, amoxicillin, fluoroquinolones, penicillin, and tylosin). Furthermore, the risk of experiencing NPD was found to be higher in herds with >200 sows (OR = 4.0) compared to herds with <200 sows and in herds where more ambitious efforts (such as providing supplemental colostrum or practicing split-suckling) were made to save weak-born piglets (OR = 4.4).Conclusions: The results of the present study indicate that Swedish farmers commonly experience NPD in their herds, often despite vaccination against ETEC. Considering the extent of this problem and its contribution to antimicrobial usage, improving alternative control strategies for NPD needs to be prioritized.
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| 7. |
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| 8. |
- Larsson, Jenny, et al.
(författare)
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Pathological and bacteriological characterization of neonatal porcine diarrhoea of uncertain aetiology
- 2015
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 64, s. 916-926
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal porcine diarrhoea of uncertain aetiology has been reported from a number of countries. This study investigated 50 diarrhoeic and 19 healthy piglets from 10 affected Swedish herds. The piglets were blood-sampled for analysis of serum gamma-globulin and necropsied, and the intestines were sampled for histopathology and cultured for Escherichia coli, Clostridium perfringens and Clostridium difficile. Escherichia coli isolates (n=276) were examined by PCR for virulence genes encoding LT, STa, STb, EAST1, VT2e, F4, F5, F6, F18, F41, AIDA-I, intimin, and for the genes aaiC and aggR. Selected isolates were analysed for additional virulence genes by a microarray and subjected to O-typing. Clostridium perfringens isolates (n=152) were examined by PCR for genes encoding major toxins, enterotoxin and beta2-toxin. There was no difference in serum gamma-globulin concentration between diarrhoeic and non-diarrhoeic piglets, and pathological lesions in the intestines were generally mild. Porcine enterotoxigenic Escherichia coli, a common cause of piglet diarrhoea, was only found in two piglets. Further, the virulence gene profiling did not suggest involvement of other diarrhoeogenic pathotypes of Escherichia coli. Growth of Clostridium perfringens did not differ between diarrhoeic and non-diarrhoeic piglets. All isolates were type A, all were negative for enterotoxin, and 151 of 152 isolates were beta2-toxin positive. In pigs >= 2 days old, moderate to profuse growth of Clostridium difficile was more common in the controls. In conclusion, it was not possible to relate Escherichia coli, Clostridium perfringens type A and C or Clostridium difficile to neonatal porcine diarrhoea in any of the investigated herds.
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| 9. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 10. |
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| 11. |
- Mahdessian, Diana, 1984-, et al.
(författare)
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An image-based map of the human mitochondrial proteome and its heterogeneity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Mitochondria is involved in a numerous variety of cellular functions beyond its role in energy metabolism. Defining the human mitochondrial proteome is crucial to understand the mitochondria’s diverse functions and role in disease. Here, we present an image-based map of the human mitochondrial proteome containing 1,098 proteins. The single cell resolution revealed extensive heterogeneity for as much as 20% (n=226) of the mitochondrial proteome. These variations are independent of cell cycle position and likely represent metabolic fluctuations in the cell. Our analysis shows that 48% (n=524) of the proteins localize to additional cellular compartments, further contributing to the diverse cellular functions of mitochondria. This map of the mitochondrial proteome, part of the Cell Atlas of the Human Protein Atlas database (www.proteinatlas.org), provides a valuable knowledge resource for studies of mitochondria function, dysfunction and disease.
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| 12. |
- Mahdessian, Diana, et al.
(författare)
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Profiling the human cytoplasmic proteome.
- 2016
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Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 14. |
- Parry, Rhys, et al.
(författare)
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Identification and RNAi Profile of a Novel Iflavirus Infecting Senegalese Aedes vexans arabiensis Mosquitoes
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The inland floodwater mosquito Aedes vexans (Meigen, 1830) is a competent vector of numerous arthropod-borne viruses such as Rift Valley fever virus (Phenuiviridae) and Zika virus (Flaviviridae). Aedes vexans spp. have widespread Afrotropical distribution and are common European cosmopolitan mosquitoes. We examined the virome of Ae. vexans arabiensis samples from Barkedji village, Senegal, with small RNA sequencing, bioinformatic analysis, and RT-PCR screening. We identified a novel 9494 nt iflavirus (Picornaviridae) designated here as Aedes vexans iflavirus (AvIFV). Annotation of the AvIFV genome reveals a 2782 amino acid polyprotein with iflavirus protein domain architecture and typical iflavirus 5' internal ribosomal entry site and 3' poly-A tail. Aedes vexans iflavirus is most closely related to a partial virus sequence from Venturia canescens (a parasitoid wasp) with 56.77% pairwise amino acid identity. Analysis of AvIFV-derived small RNAs suggests that AvIFV is targeted by the exogenous RNA interference pathway but not the PIWI-interacting RNA response, as similar to 60% of AvIFV reads corresponded to 21 nt Dicer-2 virus-derived small RNAs and the 24-29 nt AvIFV read population did not exhibit a "ping-pong" signature. The RT-PCR screens of archival and current (circa 2011-2020) Ae. vexans arabiensis laboratory samples and wild-caught mosquitoes from Barkedji suggest that AvIFV is ubiquitous in these mosquitoes. Further, we screened wild-caught European Ae. vexans samples from Germany, the United Kingdom, Italy, and Sweden, all of which tested negative for AvIFV RNA. This report provides insight into the diversity of commensal Aedes viruses and the host RNAi response towards iflaviruses.
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| 15. |
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| 16. |
- Rydell, Andreas, et al.
(författare)
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Cardiovascular disease-linked plasma proteins are mainly associated with lung volume
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity.CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.
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| 17. |
- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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| 18. |
- Theorell-Haglöw, Jenny, et al.
(författare)
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Sleep duration is associated with protein biomarkers for cardiometabolic health : A large-scale population study
- 2021
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Ingår i: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 30:5
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Tidskriftsartikel (refereegranskat)abstract
- Sleep problems and short sleep duration have been linked to adverse health effects, such as cardiovascular disease and diabetes, but the mechanisms are not fully understood. Finding biomarkers could explain mechanistic pathways and help in understanding relationships between sleep and cardiometabolic health. The aim was to assess if sleep duration and sleep quality affect the cardiometabolic-related protein profile. In total, 242 proteins related to cardiometabolic health were measured in 2,430 plasma samples (male:female ratio 1:1, aged 45–75 years) from the population-based EpiHealth cohort, using a proximity extension assay. The association of self-reported sleep duration and sleep quality with each of the 242 proteins (primary outcome) was assessed with linear regression modelling, adjusting for confounders, and corrected for multiple testing using the false discovery rate (5%). Potential effect modification of age and sex was also tested using an interaction term. We identified U-shaped associations between sleep duration and the plasma levels of the proteins follistatin (more prominent in younger individuals), matrix metallopeptidase 9 (men only), urokinase receptor, adrenomedullin and kidney injury molecule, all previously known to be related to cardiovascular risk. There was no relationship between sleep quality and any of the proteins, after adjustment for confounders. These results give new leads to investigate the potential mechanistic pathways between sleep and cardiometabolic health.
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| 19. |
- Thul, Peter J., et al.
(författare)
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A subcellular map of the human proteome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
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Tidskriftsartikel (refereegranskat)abstract
- Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.
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| 20. |
- Thul, Peter, et al.
(författare)
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Multilocalizing Human Proteins
- 2018
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Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 29:26
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Tilling, Kate, et al.
(författare)
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Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer : a comparison of observational cohorts
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:3, s. 446-452
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. OBJECTIVE: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. DESIGN, SETTING, AND PARTICIPANTS: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. MEASUREMENTS: PSA level. RESULTS AND LIMITATIONS: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: -2.0 ng/ml; interquartile range [IQR]: -7.6-0.7 ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: -0.8 ng/ml; IQR: -2.1-0.1 ng/ml). CONCLUSIONS: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols.
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| 22. |
- Visvanathar, Robin, 1994-, et al.
(författare)
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Genetic Variation and Sex-Stratified Advanced Body Composition Analysis : Neck-to-Knee MRI and Genetics in the UK Biobank
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background The heritability of body composition has been studied extensively by researchers. However, few studies have explored the genetic variation of advanced body composition phenotypes derived from magnetic resonance imaging (MRI). In this study, polygenic risk scores (PRS) and single nucleotide polymorphisms (SNPs) that are associated with image-derived features from water- and fat separated MRI are reported. Method and materials The analysis was performed with the image processing framework Imiomics to attain spatial normalisation of large imaging cohorts from the UK Biobank. The study included 13,300 men and 13,849 women following GWAS and image data quality controls. Imiomics was further applied to generate voxel-wise Pearson correlation coefficient volumes. Relative effect sizes from six SNPs (rs1358980-T, rs1936805-T, rs2820443-C, rs6567160-C, rs10195252-C and rs13021737-G) were examined for associations with segmented tissue volumes and tissue fat fractions. In addition, the LDpred-derived PRS were compared with genome-wide significant only derived PRS for body mass index (BMI), waist-to-hip ratio (WHR) and height. Results Imiomics and GWAS integration delivered a detailed mapping of individual SNPs to the tissue volume and fat fraction of regional adipose tissue depots, heart, liver, lungs and thigh muscle. A putatively less harmful relationship between gluteofemoral SAT and the two obesity-related SNPs, rs6567160-C and rs1936805-T, compared with other tissues was found. The genetic variant, rs1358980-T, located upstream of VEGFA, was the highest ranked SNP inversely associated with gluteofemoral SAT volume in both sexes (r= -0.0245, p<0.05 and r= -0.0257, p<0.05 in men and women, respectively). Observed effect sizes were overall higher with LDpred-derived PRS compared with genome-wide significant only scores. Conclusion An image-based exploratory integration approach guided by Imiomics enabled efficient and large-scale analysis of advanced body composition and genetic variation.
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| 23. |
- Wiking, Mikaela, et al.
(författare)
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Drafting the intermediate filament proteome
- 2016
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Ingår i: Molecular Biology of the Cell. - : American society of cell biology. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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