| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Jones, Benedict C, et al.
(author)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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In: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Journal article (peer-reviewed)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 6. |
- Lee, Sunjae, et al.
(author)
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Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance
- 2016
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 24:1, s. 172-184
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Journal article (peer-reviewed)abstract
- To investigate the biological processes that are altered in obese subjects, we generated cell-specific integrated networks (INs) by merging genome-scale metabolic, transcriptional regulatory and protein-protein interaction networks. We performed genome-wide transcriptomics analysis to determine the global gene expression changes in the liver and three adipose tissues from obese subjects undergoing bariatric surgery and integrated these data into the cell-specific INs. We found dysregulations in mannose metabolism in obese subjects and validated our predictions by detecting mannose levels in the plasma of the lean and obese subjects. We observed significant correlations between plasma mannose levels, BMI, and insulin resistance (IR). We also measured plasma mannose levels of the subjects in two additional different cohorts and observed that an increased plasma mannose level was associated with IR and insulin secretion. We finally identified mannose as one of the best plasma metabolites in explaining the variance in obesity-independent IR.
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| 7. |
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| 8. |
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| 9. |
- Piening, B. D., et al.
(author)
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Integrative Personal Omics Profiles during Periods of Weight Gain and Loss
- 2018
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In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 6:2
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Journal article (peer-reviewed)abstract
- Advances in omics technologies now allow an unprecedented level of phenotyping for human diseases, including obesity, in which individual responses to excess weight are heterogeneous and unpredictable. To aid the development of better understanding of these phenotypes, we performed a controlled longitudinal weight perturbation study combining multiple omics strategies (genomics, transcriptomics, multiple proteomics assays, metabolomics, and microbiomics) during periods of weight gain and loss in humans. Results demonstrated that: (1) weight gain is associated with the activation of strong inflammatory and hypertrophic cardiomyopathy signatures in blood; (2) although weight loss reverses some changes, a number of signatures persist, indicative of long-term physiologic changes; (3) we observed omics signatures associated with insulin resistance that may serve as novel diagnostics; (4) specific biomolecules were highly individualized and stable in response to perturbations, potentially representing stable personalized markers. Most data are available open access and serve as a valuable resource for the community.
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| 10. |
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| 11. |
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| 12. |
- Lovric, Alen, et al.
(author)
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Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome
- 2018
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Journal article (peer-reviewed)abstract
- Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.
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| 13. |
- Mardinoglu, Adil, 1982, et al.
(author)
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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
- 2018
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:3
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Journal article (peer-reviewed)abstract
- A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
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| 14. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Personal model-assisted identification of NAD(+) and glutathione metabolism as intervention target in NAFLD
- 2017
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:3
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Journal article (peer-reviewed)abstract
- To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD(+) and glutathione (GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD(+) repletion on the development of NAFLD, we added precursors for GSH and NAD(+) biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof-of-concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.
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| 15. |
- Zeybel, M., et al.
(author)
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Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
- 2021
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 17:10
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Journal article (peer-reviewed)abstract
- Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.
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| 16. |
- Choi, M. J., et al.
(author)
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An adipocyte-specific defect in oxidative phosphorylation increases systemic energy expenditure and protects against diet-induced obesity in mouse models
- 2020
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428.
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Mitochondrial oxidative phosphorylation (OxPhos) is essential for energy production and survival. However, the tissue-specific and systemic metabolic effects of OxPhos function in adipocytes remain incompletely understood. Methods: We used adipocyte-specific Crif1 (also known as Gadd45gip1) knockout (AdKO) mice with decreased adipocyte OxPhos function. AdKO mice fed a normal chow or high-fat diet were evaluated for glucose homeostasis, weight gain and energy expenditure (EE). RNA sequencing of adipose tissues was used to identify the key mitokines affected in AdKO mice, which included fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). For in vitro analysis, doxycycline was used to pharmacologically decrease OxPhos in 3T3L1 adipocytes. To identify the effects of GDF15 and FGF21 on the metabolic phenotype of AdKO mice, we generated AdKO mice with global Gdf15 knockout (AdGKO) or global Fgf21 knockout (AdFKO). Results: Under high-fat diet conditions, AdKO mice were resistant to weight gain and exhibited higher EE and improved glucose tolerance. In vitro pharmacological and in vivo genetic inhibition of OxPhos in adipocytes significantly upregulated mitochondrial unfolded protein response-related genes and secretion of mitokines such as GDF15 and FGF21. We evaluated the metabolic phenotypes of AdGKO and AdFKO mice, revealing that GDF15 and FGF21 differentially regulated energy homeostasis in AdKO mice. Both mitokines had beneficial effects on obesity and insulin resistance in the context of decreased adipocyte OxPhos, but only GDF15 regulated EE in AdKO mice. Conclusions/interpretation: The present study demonstrated that the adipose tissue adaptive mitochondrial stress response affected systemic energy homeostasis via cell-autonomous and non-cell-autonomous pathways. We identified novel roles for adipose OxPhos and adipo-mitokines in the regulation of systemic glucose homeostasis and EE, which facilitated adaptation of an organism to local mitochondrial stress.
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| 17. |
- Das, P., et al.
(author)
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Exotic decay of 115Cs
- 2023
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In: Physical Review C. - 2469-9985. ; 108:6
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Journal article (peer-reviewed)abstract
- The detailed study of the β+/EC decay of the very neutron-deficient and alpha-unbound nucleus 115Cs is presented. The measurement was performed at the ISOLDE, CERN where delayed charged particles and γ rays were detected. The observed delayed γ rays are in agreement with the previously reported characteristics γ rays of 115Xe. Based on the experimental observations, the tentative ground-state spin of 115Cs is suggested to be 7/2+ or 9/2+. Furthermore, the measured decay branching ratio of delayed protons exceeds the previously reported value. Additionally, new delayed α-branching ratio and several reconstructed proton and α-unbound excited states of 115Xe are being reported for the first time. The properties of proton-unbound states at excitation energies from 3.9–7.9 MeV have been obtained by fitting the delayed proton spectrum via the Bayesian method. The measured lifetimes of these proton-unbound states are in the order of zeptoseconds.
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| 18. |
- Finucane, Mariel M, et al.
(author)
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National, regional, and global trends in body-mass index since 1980 : systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants
- 2011
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9765, s. 557-567
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Journal article (peer-reviewed)abstract
- BACKGROUND: Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI. METHODS: We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. FINDINGS: Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m(2) per decade (95% uncertainty interval 0·2-0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m(2) per decade (0·3-0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m(2) per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m(2) per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m(2) (32·8-35·0) for men and 35·0 kg/m(2) (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m(2), 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m(2) (18·2-21·5), with BMI less than 21·5 kg/m(2) for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m(2) or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. INTERPRETATION: Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. FUNDING: Bill & Melinda Gates Foundation and WHO.
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| 19. |
- Jin, Han, et al.
(author)
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Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability
- 2024
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Metabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking. Methods: In this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque. Results: Our study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH−) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment. Conclusions: This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.
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| 20. |
- Lakens, Daniel, et al.
(author)
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Justify your alpha
- 2018
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In: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Journal article (peer-reviewed)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 21. |
- Smati, S., et al.
(author)
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Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
- 2022
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In: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 71:4, s. 807-821
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Journal article (peer-reviewed)abstract
- We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans. Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver. The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα. These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target. NCT02390232.
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| 22. |
- Strosberg, Jonathan, et al.
(author)
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Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- 2020
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 47:10, s. 2372-2382
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Journal article (peer-reviewed)abstract
- Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11
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| 23. |
- Thul, Peter J., et al.
(author)
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A subcellular map of the human proteome
- 2017
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In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
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Journal article (peer-reviewed)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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| 24. |
- Uhlén, Mathias, et al.
(author)
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The human secretome
- 2019
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In: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Journal article (peer-reviewed)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 25. |
- Zeybel, M., et al.
(author)
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Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis
- 2022
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In: Advanced Science. - : Wiley. - 2198-3844. ; 9:11, s. 2104373-
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Journal article (peer-reviewed)abstract
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host–microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.
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| 26. |
- Abdellah, Tebani, et al.
(author)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 27. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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Synedropsis abuflosensis sp. nov., a new araphid diatom (Bacillariophyceae) from the Shatt Al-Arab River, Southern Iraq
- 2022
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In: Cryptogamie Algologie. - : Museum National d'Histoire Naturelle, Paris, France. - 0181-1568. ; 43:2, s. 31-39
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Journal article (peer-reviewed)abstract
- Synedropsis abuflosensis sp. nov. is the third species of the genus recorded from a sub-tropical brackish water habitat as opposed to a polar distribution. This species is differentiated from others in the genus by having a different number of slits in the apical slit field at opposite ends of the valve (i.e., 4 at the end possessing a rimoportula versus 5 at the end lacking a rimoportula), an apically oriented rimoportula and 3-4 non-porous cingular bands. Its habitat is different than that of all known Synedropsis Hasle, Medlin & Syvertsen species as it is either benthic or epiphytic in algal mats rather than planktonic or associated with sea ice. The new species was found in waters with a conductivity of 7.1 mu S (cm-1) (salinity 3.3 psu) and a temperature of 33 degrees C. Morphological characters of the new species are described based on light and scanning electron microscopy observations. A comparison of S. abuflosensis sp. nov. with morphologically similar species is provided.
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| 28. |
- De Tommasi, E., et al.
(author)
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Underwater Light Manipulation by the Benthic Diatom Ctenophora pulchella: From PAR Efficient Collection to UVR Screening
- 2021
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In: Nanomaterials. - : MDPI AG. - 2079-4991. ; 11:11
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Journal article (peer-reviewed)abstract
- Several species of diatoms, unicellular microalgae which constitute the main component of phytoplankton, are characterized by an impressive photosynthetic efficiency while presenting a noticeable tolerance versus exposure to detrimental UV radiation (UVR). In particular, the growth rate of the araphid diatom Ctenophora pulchella is not significantly affected by harsh treatments with UVR, even in absence of detectable, specific UV-absorbing pigments and even if it is not able to avoid high UV exposure by motility. In this work we applied a multi-disciplinary approach involving numerical computation, photonics, and biological parameters in order to investigate the possible role of the frustule, micro- and nano-patterned silica shell which encloses the cell, in the ability of C. pulchella to efficiently collect photosynthetic active radiation (PAR) and to simultaneously screen the protoplasm from UVR. The characterization of the photonic properties of the frustule has been accompanied by in vivo experiments conducted in water in order to investigate its function as optical coupler between light and plastids.
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| 29. |
- Fagerberg, Linn, et al.
(author)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Journal article (peer-reviewed)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 30. |
- Grinberg, Marianna, et al.
(author)
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Toxicogenomics directory of chemically exposed human hepatocytes
- 2014
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In: Archives of Toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 88:12, s. 2261-2287
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Journal article (peer-reviewed)abstract
- A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes.
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| 31. |
- Lee, SangWook, et al.
(author)
-
Network analyses identify liver-specific targets for treating liver diseases
- 2017
-
In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:8
-
Journal article (peer-reviewed)abstract
- We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.
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| 32. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
- 2018
-
In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 27, s. 151-155
-
Journal article (peer-reviewed)abstract
- Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.
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| 33. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Plasma Mannose Levels Are Associated with Incident Type 2 Diabetes and Cardiovascular Disease
- 2017
-
In: Cell Metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 26:2, s. 281-283
-
Journal article (other academic/artistic)abstract
- Plasma mannose levels are elevated in subjects with insulin resistance independently of obesity. Here, we found that elevated plasma mannose levels are strong markers of future risk of several chronic diseases including T2D, CVD, and albuminuria, and that it may contribute to their development rather than just being a novel biomarker.
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| 34. |
- Satia, Imran, et al.
(author)
-
Emergency department visits and hospitalisations for asthma, COPD and respiratory tract infections : what is the role of respiratory viruses, and return to school in September, January and March?
- 2020
-
In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
-
Journal article (peer-reviewed)abstract
- Background: Asthma exacerbations increase in September coinciding with children returning to school. The aim of this study was to investigate whether this occurs 1) for COPD and respiratory tract infections (RTIs); 2) after school resumes in January and March; and 3) identify which viruses may be responsible.Methods: Emergency department (ED) visits and admissions for asthma, COPD and RTIs and the prevalence of viruses in Ontario, Canada were analysed daily between 2003 and 2013. ED visits and admissions were provided by the Canadian Institute for Health Information. Viral prevalence was obtained from the Centre for Immunisation and Respiratory Infectious Diseases.Results: ED visits and admissions rates demonstrated a biphasic pattern. Lowest rates occurred in July and August and the highest rates in September for asthma, and after December for COPD and RTI. The increase in rates for 30 days before and after school return in September was greatest for children with asthma <15 years (2.4-2.6×). Event rates fell after school return in January for all three conditions ranging from 10-25%, and no change followed March break for asthma and COPD. Human rhinovirus was prevalent in summer with a modest relationship to asthma rates in September. The prevalence of respiratory syncytial virus, influenza A and coronavirus was associated with sustained event rates for COPD and RTIs.Conclusions: Asthma, COPD and RTIs increase in September but do not occur after return to school in January and March. Human rhinovirus is associated with ED visits and admissions only in September.
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| 35. |
- Sayitoglu, Ece Canan, et al.
(author)
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Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D
- 2020
-
In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
-
Journal article (peer-reviewed)abstract
- Sarcomas are malignancies of mesenchymal origin that occur in bone and soft tissues. Many are chemo- and radiotherapy resistant, thus conventional treatments fail to increase overall survival. Natural Killer (NK) cells exert anti-tumor activity upon detection of a complex array of tumor ligands, but this has not been thoroughly explored in the context of sarcoma immunotherapy. In this study, we investigated the NK cell receptor/ligand immune profile of primary human sarcoma explants. Analysis of tumors from 32 sarcoma patients identified the proliferative marker PCNA and DNAM-1 ligands CD112 and/or CD155 as commonly expressed antigens that could be efficiently targeted by genetically modified (GM) NK cells. Despite the strong expression of CD112 and CD155 on sarcoma cells, characterization of freshly dissociated sarcomas revealed a general decrease in tumor-infiltrating NK cells compared to the periphery, suggesting a defect in the endogenous NK cell response. We also applied a functional screening approach to identify relevant NK cell receptor/ligand interactions that induce efficient anti-tumor responses using a panel NK-92 cell lines GM to over-express 12 different activating receptors. Using GM NK-92 cells against primary sarcoma explants (n = 12) revealed that DNAM-1 over-expression on NK-92 cells led to efficient degranulation against all tested explants (n = 12). Additionally, NKG2D over-expression showed enhanced responses against 10 out of 12 explants. These results show that DNAM-1(+) or NKG2D(+) GM NK-92 cells may be an efficient approach in targeting sarcomas. The degranulation capacity of GM NK-92 cell lines was also tested against various established tumor cell lines, including neuroblastoma, Schwannoma, melanoma, myeloma, leukemia, prostate, pancreatic, colon, and lung cancer. Enhanced degranulation of DNAM-1(+) or NKG2D(+) GM NK-92 cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1(+) or NKG2D(+) GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.
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| 36. |
- Sork, Helena, et al.
(author)
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Lipid-based Transfection Reagents Exhibit Cryo-induced Increase in Transfection Efficiency
- 2016
-
In: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 5
-
Journal article (peer-reviewed)abstract
- The advantages of lipid-based transfection reagents have permitted their widespread use in molecular biology and gene therapy. This study outlines the effect of cryo-manipulation of a cationic lipid-based formulation, Lipofectamine 2000, which, after being frozen and thawed, showed orders of magnitude higher plasmid delivery efficiency throughout eight different cell lines, without compromising cell viability. Increased transfection efficiency with the freeze-thawed reagent was also seen with 2'-O-methyl phosphorothioate oligonucleotide delivery and in a splice-correction assay. Most importantly, a log-scale improvement in gene delivery using the freeze-thawed reagent was seen in vivo. Using three different methods, we detected considerable differences in the polydispersity of the different nucleic acid complexes as well as observed a clear difference in their surface spreading and sedimentation, with the freeze-thawed ones displaying substantially higher rate of dispersion and deposition on the glass surface. This hitherto overlooked elevated potency of the freeze-thawed reagent facilitates the targeting of hard-to-transfect cells, accomplishes higher transfection rates, and decreases the overall amount of reagent needed for delivery. Additionally, as we also saw a slight increase in plasmid delivery using other freeze-thawed transfection reagents, we postulate that freeze-thawing might prove to be useful for an even wider variety of transfection reagents.
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| 37. |
- Turkez, H., et al.
(author)
-
In vitro transcriptome response to propolis in differentiated SH-SY5Y neurons
- 2021
-
In: Journal of food biochemistry. - : Wiley. - 0145-8884 .- 1745-4514. ; 45:12
-
Journal article (peer-reviewed)abstract
- Propolis is the extract of a resinous compound that protects plants from both cold and microorganism attack and has gained a strong and sticky property because it is transformed after being collected by honey bees. Up to date, many studies have shown that propolis exhibited various beneficial biological activities, such as antifungal, antibacterial, antiviral, antioxidant, antimutagenic, and antitumor effects. Recent reports propounded the in vitro and in vivo neuroprotective effect of propolis; however, the exact molecular genetic mechanisms are still unclear. Therefore, we aimed to investigate the toxicogenomic and beneficial properties, including cytotoxic, antioxidant, apoptotic/necrotic as well as genotoxic effects of propolis (1.56–200 µg/ml) on differentiated SH-SY5Y neuronal cells. Additionally, microarray analysis was conducted on cell cultures following propolis application to explore gene differentiation. Differentially expressed genes were further analyzed using string software to characterize protein–protein interactions between gene pathways. Our results revealed that propolis applications could not have a prominent effect on cell viability even at concentrations up to 200 µg/ml. The highest propolis concentration induced apoptotic rather than necrotic cell death. The alterations in gene expression profiles, including CYP26A1, DHRS2, DHRS3, DYNC1I1, IGF2, ITGA4, SVIL, TGFβ1, and TGM2 could participate in the neuroprotective effects of propolis. In conclusion, propolis supplementation exerted remarkable advantageous; thus, it may offer great potential as a natural component in the prevention and treatment of neurodegenerative disorders. Whole-genome gene expression pattern following propolis application was investigated for the first time in neuronal cell culture to fill a gap in the literature about propolis toxicogenomics. Practical applications: Propolis is a very rich product in terms of benefits. In addition to its antibacterial, antiviral, antifungal, and anti-inflammatory content, it is known to have preventive and therapeutic properties for many different ailments. On the other hand, molecular mechanisms of propolis on gene expression differentiations haven't been investigated until now. Moreover, gene expression pattern is vital for all living organisms to maintain homeostasis. Thus, we conduct an experiment series for analyzing gene expression differentiation effects on neuronal cells to understand beneficial properties of propolis. Hence, it could be possible to comment on the use of propolis as a nutritional factor and beneficial diet.
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| 38. |
- Uhlén, Mathias, et al.
(author)
-
A pathology atlas of the human cancer transcriptome
- 2017
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 357:6352, s. 660-
-
Journal article (peer-reviewed)abstract
- Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.
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| 39. |
- Uhlén, Mathias, et al.
(author)
-
Tissue-based map of the human proteome
- 2015
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220, s. 1260419-
-
Journal article (peer-reviewed)abstract
- Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.
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| 40. |
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| 41. |
- Aarrestad, Thea, et al.
(author)
-
Benchmark data and model independent event classification for the large hadron collider
- 2022
-
In: SciPost Physics. - 2542-4653. ; 12:1
-
Journal article (peer-reviewed)abstract
- We describe the outcome of a data challenge conducted as part of the Dark Machines (https://www.darkmachines.org) initiative and the Les Houches 2019 workshop on Physics at TeV colliders. The challenged aims to detect signals of new physics at the Large Hadron Collider (LHC) using unsupervised machine learning algorithms. First, we propose how an anomaly score could be implemented to define model-independent signal regions in LHC searches. We define and describe a large benchmark dataset, consisting of > 1 billion simulated LHC events corresponding to 10 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV. We then review a wide range of anomaly detection and density estimation algorithms, developed in the context of the data challenge, and we measure their performance in a set of realistic analysis environments. We draw a number of useful conclusions that will aid the development of unsupervised new physics searches during the third run of the LHC, and provide our benchmark dataset for future studies at https://www.phenoMLdata.org. Code to reproduce the analysis is provided at https://github.com/bostdiek/DarkMachines-UnsupervisedChallenge.
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| 42. |
- Al-Babtain, Ibrahim, et al.
(author)
-
Maintenance and repair of highway concrete bridges : A case study
- 1991
-
In: Proceedings of Strategic Highway Research Program and Traffic Safety on Two Continents. Conference in Gothenburg, Sweden, September 18-20, 1991. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 217-241
-
Conference paper (other academic/artistic)
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| 43. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Entomoneis annagodheisp. nov., a new marine diatom (Entomoneidaceae, Bacillariophyta) from the west coast of Sweden
- 2020
-
In: Diatom Research. - : Informa UK Limited. - 0269-249X .- 2159-8347. ; 35:3, s. 269-279
-
Journal article (peer-reviewed)abstract
- The genusEntomoneisincludes diatoms with an elevated bilobate keel, a sigmoid raphe canal and numerous girdle bands. It is known to inhabit various environments, from freshwater to marine, both plankton and benthos. During a phytoplankton investigation in the Kungalv estuary on the west coast of Sweden, we observed numerous cells belonging toEntomoneis. Further morphological investigations performed with light and electron microscopy allowed us to describeEntomoneis annagodhei, sp. nov., with a unique set of morphological characters. Most importantly, a still undocumented character proved to be an oblique transapical fascia across the centre of the valve. Other distinctive features of this species are a pronounced raphe canal with dense raphe fibulae, very fine striation, resolvable only with electron microscopy, external lanceolate slit-like opening of the central nodule, and fine, linear to undulate external ridges running more or less parallel and adjacent to the raphe and valve margin. The morphological characters and morphometry are discussed in comparison with similar taxa. Our results contribute to the under-appreciated diversity ofEntomoneis, especially inhabiting the marine plankton.
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| 44. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Entomoneis grisslehamnensis, a New Diatom (Bacillariophyceae) from the Baltic Coast of Sweden with taxonomic and ecological notes on Entomoneis paludosa (W. Smith) Reimer
- 2023
-
In: Diatom Research. - 0269-249X. ; 38:1, s. 55-68
-
Journal article (peer-reviewed)abstract
- The diatom genus Entomoneis includes species with panduriform frustules characterized by a bilobate, elevated keel, sigmoid raphe canal and numerous open, porous girdle bands. During a phytoplankton survey along the Baltic coast of Sweden, we observed numerous Entomoneis cells, some belonging to the well-known Entomoneis paludosa, while others remained unknown. Morphological and ultrastructural studies of the unknown species were performed with light microscopy (LM), scanning (SEM) and transmission (TEM) electron microscopy, and revealed a unique set of morphological characters. Live cells of Entomoneis grisslehamnensis sp. nov. contain one plate-like plastid and show various degrees of torsion about the apical axis. Microscopic features of cleaned frustules are discussed in comparison with similar species. Most importantly, every 2nd to 5th virga is strongly elevated, uniseriate striae are composed of quadrangular areolae with finely perforated hymenes; the winged keel with a discernible raphe canal is structurally strengthened by raphe fibulae with a flattened wing area, and the main part of the valve bulges towards the margins; striation is decussate on the wings and there is one row of raphe canal areolae at the central area. In addition to describing this new species of an underappreciated, yet cosmopolitan diatom genus, we contribute to the taxonomy of E. paludosa with LM, SEM and TEM details, some of which were not sufficiently noted in original descriptions or re-examination of type material and other specimens made by Dalu et al. [2015. A re-examination of the type material of Entomoneis paludosa (W. Smith) Reimer and its morphology and distribution in African waters. Fottea 15: 11-25] and Long et al. [2022. Ultrastructure of three species of Entomoneis (Bacillariophyta) from Lake Qinghai of China, with reference to the external areola occlusions.
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| 45. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Fallacia fawensis sp. nov., a new brackish water diatom (Bacillariophyceae) from Southern Iraq
- 2022
-
In: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 550:1, s. 71-78
-
Journal article (peer-reviewed)abstract
- The diatom genus Fallacia includes species having a conopeum which is a perforated thin sheath of silica lying along the apical axis on the external valve face and a hyaline lateral area in the internal valve face. In surveying the benthic diatoms of Basra, a new small brackish water species, Fallacia fawensis was found associated with fine-grained substrata on the western bank of Shatt Al???Arab River, Southern Iraq. This epipelic species is described based on light and scanning electron microscopy and characterized by having a porous conopeum covering the area between raphe sterna and mantle, narrow elongated marginal striae, and a structure similar to lateral hyaline areas in the valve internal side. The terminal raphe endings on the external valve face, below valve apex, the raphe sternum inner margins come close to each other, blocking raphe canal but leaving a lacuna-like thin groove for connection with the deflected upper part of the open raphe canal. These features separated this species from allied taxa of the genus and also from closely related genera, Pseudofallacia and Germaniella. Notes on the ecology and distribution of the new species as well as the associated diatom taxa are provided.
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| 46. |
- Alomar, Mohamed Khalid, et al.
(author)
-
Data-driven models for atmospheric air temperature forecasting at a continental climate region
- 2022
-
In: PLOS ONE. - : Public Library of Science, PLOS. - 1932-6203. ; 17:11
-
Journal article (peer-reviewed)abstract
- Atmospheric air temperature is the most crucial metrological parameter. Despite its influence on multiple fields such as hydrology, the environment, irrigation, and agriculture, this parameter describes climate change and global warming quite well. Thus, accurate and timely air temperature forecasting is essential because it provides more important information that can be relied on for future planning. In this study, four Data-Driven Approaches, Support Vector Regression (SVR), Regression Tree (RT), Quantile Regression Tree (QRT), ARIMA, Random Forest (RF), and Gradient Boosting Regression (GBR), have been applied to forecast short-, and mid-term air temperature (daily, and weekly) over North America under continental climatic conditions. The time-series data is relatively long (2000 to 2021), 70% of the data are used for model calibration (2000 to 2015), and the rest are used for validation. The autocorrelation and partial autocorrelation functions have been used to select the best input combination for the forecasting models. The quality of predicting models is evaluated using several statistical measures and graphical comparisons. For daily scale, the SVR has generated more accurate estimates than other models, Root Mean Square Error (RMSE = 3.592°C), Correlation Coefficient (R = 0.964), Mean Absolute Error (MAE = 2.745°C), and Thiels’ U-statistics (U = 0.127). Besides, the study found that both RT and SVR performed very well in predicting weekly temperature. This study discovered that the duration of the employed data and its dispersion and volatility from month to month substantially influence the predictive models’ efficacy. Furthermore, the second scenario is conducted using the randomization method to divide the data into training and testing phases. The study found the performance of the models in the second scenario to be much better than the first one, indicating that climate change affects the temperature pattern of the studied station. The findings offered technical support for generating high-resolution daily and weekly temperature forecasts using Data-Driven Methodologies.
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| 47. |
- Altay, Özlem, et al.
(author)
-
Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
- 2021
-
In: Advanced Science. - : Wiley. - 2198-3844. ; 8:17
-
Journal article (peer-reviewed)abstract
- COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
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| 48. |
- Arif, Muhammad, et al.
(author)
-
Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction
- 2021
-
In: Elife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 10
-
Journal article (peer-reviewed)abstract
- Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genomewide transcriptomic analysis on tissue samples obtained 6- and 24 hr post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.
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| 49. |
- Arslan, M. E., et al.
(author)
-
In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer’s disease model of differentiated neuroblastoma cell line
- 2020
-
In: International Journal of Neuroscience. - : Taylor and Francis Ltd. - 0020-7454 .- 1563-5279 .- 1543-5245.
-
Journal article (peer-reviewed)abstract
- Objective: To investigate neuroprotective properties of the farnesene sesquiterpene on the experimental Alzheimer’s disease model in vitro. Methods: Human neuroblastoma cell line (SHSY-5Y) was differentiated into neuron-like cells by using retinoic acid to constitute the in vitro Alzheimer’s Disease model. β-amyloid 1-42 protein was applied to the transformed cells for 24 and 48 hours in a wide dose ranges (3.125-200 μM) to establish AD cytotoxicity. Then, farnesene was applied to cell cultures in a wide spectrum dose interval (1.625-100 μg/ml) to investigate neuroprotective effect against β-amyloid for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were executed to determine cytotoxicity in the Alzheimer model. Nuclear DNA integrity of cells was examined under the fluorescent microscope using the Hoechst 33258 staining method. Furthermore, acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were analyzed to understand the protection mechanism of the farnesene application on the cell culture model. Finally, flow cytometry analysis was used to find out the cell death mechanism after beta-amyloid and farnesene application to the cell culture. Results: Cell viability tests revealed significant neuroprotection against β-amyloid toxicity in both 24 and 48 hours and the Hoechst 33258 fluorescence staining method showed a significant decrease in necrotic deaths after farnesene application in the cell cultures. Finally, flow cytometry analysis put forth that farnesene could decrease necrotic cell death up to 3-fold resulted from beta-amyloid exposure. Conclusion: According to the investigations, farnesene can potentially be a safe, anti-necrotic and neuroprotective agents against Alzheimer’s disease.
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| 50. |
- Baboota, Ritesh, et al.
(author)
-
BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH
- 2022
-
In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:8, s. 1007-21
-
Journal article (peer-reviewed)abstract
- The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets. Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.
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