| 1. |
- De Leoz, M. L. A., et al.
(författare)
-
NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
-
Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
|
|
| 2. |
- Clark, DW, et al.
(författare)
-
Associations of autozygosity with a broad range of human phenotypes
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
|
|
| 3. |
- Camuffo, I, et al.
(författare)
-
State of the art and eVALUE scope
- 2008
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- eVALUE will address the real function of ICT-based safety systems and their capability to perform the function through two courses of action: defining and quantifying the function output to be achieved by the safety system and developing the testing and evaluation methods for the ICT-based safety systems. The safety systems within the eVALUE scope are classified into four clusters: longitudinal, lateral and yaw/stability. The fourth cluster remains open for upcoming systems. Based on market availability and penetration rate, the consortium decided to focus on eight preventive or mitigating safety systems: ACC, FCW and CM by braking, in the longitudinal assistance domain; BSD, LDW and LKA, in the lateral assistance domain; and finally, ABS and ESC, in the yaw/stability assistance domain. Following the description of current test and evaluation methods, sensor technologies, system function output and ECUs globally applicable to ICT based safety systems, the report covers these technologies and components for the eight selected systems in detail. As a next step to this deliverable and according to the work plan, concepts for design reviews, physical vehicle testing as well as laboratory testing will be analysed. The result will be an in-depth understanding of the possibilities to investigate and evaluate the eight active safety systems within the first phase of the project. The different concepts will then support the decision about the development of the testing and evaluation methods that are able to point out the safety benefit of those systems in the most representative way.
|
|
| 4. |
- Gonzalez-Franquesa, Alba, et al.
(författare)
-
Discovery of thymosin β4 as a human exerkine and growth factor
- 2021
-
Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 321:5, s. 770-778
-
Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin b4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.
|
|
| 5. |
- Hedberg, Yolanda S., et al.
(författare)
-
Electrochemical surface oxide characteristics of metal nanoparticles (Mn, Cu and Al) and the relation to toxicity
- 2016
-
Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 212, s. 360-371
-
Tidskriftsartikel (refereegranskat)abstract
- Most metal nanoparticles (NPs), except noble metal NPs, rapidly form a thin surface oxide in ambient conditions. The protective properties of these oxides improve or worsen depending on the environment, e.g., the human lung. Several properties, including the chemical/electrochemical stability and defect density, determine the capacity of these surface oxides to hinder the bulk metal from further oxidation (corrosion). The aim of this study was to investigate whether electrochemical surface oxide characterization of non-functionalized base metal NPs of different characteristics (Al, Mn and Cu) can assist in understanding their bioaccessibility (metal release) in cell media (DMEM+) and their cytotoxic properties following exposure in lung epithelial (A549) cells. The composition and valence states of surface oxides of metal NPs and their electrochemical activity were investigated using an electrochemical technique based on a graphite paste electrode to perform cyclic voltammetry in buffer solutions and open circuit potential measurements in DMEM+. The electrochemical surface oxide characterization was complemented and verified by Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The open circuit potential trends in DMEM+ correlated well with metal release results in the same solution, and provided information on the kinetics of oxide dissolution in the case of Cu NPs. Extensive particle agglomeration in cell medium (DMEM+) was observed by means of photon-cross correlation spectroscopy for all metal NPs, with sedimentation taking place very quickly. As a consequence, measurements of the real dose of added non-functionalized metal NPs to cell cultures for cytotoxicity testing from a sonicated stock solution were shown necessary. The cytotoxic response was found to be strongly correlated to changes in physico-chemical and electrochemical properties of the surface oxides of the metal NPs, the most potent being Cu NPs, followed by Mn NPs. No cytotoxicity was observed for Al NPs. The electrochemical surface oxide characterization corresponded well with other tools commonly used for nanotoxicological characterization and provided additional information.
|
|
| 6. |
- Karlsson, Göran, et al.
(författare)
-
Gene expression profiling demonstrates that TGF-{beta}1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-{beta} signaling.
- 2005
-
Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 21:3, s. 396-403
-
Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-β-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.
|
|
| 7. |
- Smith, Jennifer A, et al.
(författare)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
|
|
| 8. |
|
|
| 9. |
- Ahnesjö, Jonas, 1969-, et al.
(författare)
-
Benefits of outdoor exercise and recovery outdoors in elderly
- 2019
-
Ingår i: HEPA Europe, Odense, Denmark, August 28-30, 2019. ; , s. 38-38
-
Konferensbidrag (refereegranskat)abstract
- Purpose: The purpose of this study was to test the hypothesis that the ”outdoors” has an added health effect on top of that of physical activity. This hypothesis is based on the fairly extensive volume of evidens suggesting that the outdoor environment is beneficial for overall health. We, however, consider most previous studies insufficiently designed in order to draw causal relationship between spending time outdoors and examined health parameters. In this study we state that our experimental design allows us to do just that. Methods:In this randomized cross-over experimental design, 49 healthy subjects (+65 years, 27 female) performed a standardized submaximal bike ergometer test in three different environments (indoors, simulated outdoors and outdoors). The test consisted of 20 minutes cycling and subjects were instructed to stay between 11-13 at the Borg RPE scale (i.e. moderate intensity). Each test was followed by two hours of passive recovery. We measured power output, heart rate, lactate and counts of five fractions (lymphocytes, monocytes, neutrophiles, basophiles and eosinophiles) of white blood cells (leukocytes) in circulation. Results:Our results revealed that the outdoor treatment resulted in higher levels of lactate, higher heart rate and higher power output despite that there were no differences in Borg RPE-rating between the treatments. The white blood cell analysis showed an increase of circulating leukocytes in almost all fractions immediately post exercise in all treatments. Numbers decreased rapidly post exercise and the lymphocyte numbers stayed well under baseline for more than one hour during recovery. This is referred to as an “open window” where the immune function is temporarily suppressed and there is an elevated risk of infection of primarily URTI. Conclusions:Our results not only suggest that exercise is more efficient out of doors such that more exercise/effort is obtained but also that recovery outdoors may be a way to decrease the risk of infections due to exercise induced immune suppression. The risk of getting an infection is known to be generally lower out of doors. Taken together, our results support the notion that exercising and spending time outdoors indeed is beneficial for health in senior citizens.
|
|
| 10. |
- Ahnesjö, Jonas, 1969-, et al.
(författare)
-
The effect of exercising in different environments on heart rate and power output among older adults–a randomized crossover study
- 2022
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:11
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundA growing body of evidence suggests that exposure to nature is beneficial for human health. However, the observed health effect of nature may be mediated by physical activity and that humans are physically active at a higher intensity outdoors compared to when they are physical active indoors.ObjectiveThis study examines the variation of heart rate and power output for a fixed rating of perceived exertion in a group of healthy older adults in three different environments representing three levels of exposure to nature.MethodsTo this randomized, 3-by-3 crossover design study, healthy older adults (≥65 years) were recruited from local gyms. All participants participated in three experimental conditions; indoors, simulated outdoors and outdoor environments, in a randomized order. The participants exercised for 20 minutes at an intensity equivalent to a rating of 11–13 on the Borg scale for perceived exertion (RPE). Measurements of heart rate, power output (Watt) and ratings of perceived exertion were taken at minutes 1 to 6 and at minute 20. To examine the effect of the environment on heart rate and power, linear mixed models were used.ResultsIn all, 48 participants (56% females) were included in the analysis. No significant main effects on the outcomes were observed for power output (p = 0.073, η2 = 0.04) or heart rate (p = 0.067, η2 = 0.04)ConclusionNo significant effect on the outcomes was observed. However, borderline significant outcomes for power output or heart rate outdoors in nature, along with previous studies in the field, indicates that such an effect cannot be completely ruled out, but any effect is likely to be small. Future research examining health benefits of the independent exposure to nature are encouraged to adjust for the dose of physical activity.
|
|
