| 1. |
- Bravo, L, et al.
(author)
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- 2021
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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. |
- Thomas, HS, et al.
(author)
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- 2019
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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. |
- 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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| 7. |
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| 8. |
- Baboota, Ritesh, et al.
(author)
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Chronic hyperinsulinemia promotes human hepatocyte senescence
- 2022
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In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 64
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Journal article (peer-reviewed)abstract
- Objective: Cellular senescence, an irreversible proliferative cell arrest, is caused by excessive intracellular or extracellular stress/damage. Increased senescent cells have been identified in multiple tissues in different metabolic and other aging-related diseases. Recently, several human and mouse studies emphasized the involvement of senescence in development and progression of NAFLD. Hyperinsulinemia, seen in obesity, metabolic syndrome, and other conditions of insulin resistance, has been linked to senescence in adipocytes and neurons. Here, we investigate the possible direct role of chronic hyperinsulinemia in the development of senescence in human hepatocytes. Methods: Using fluorescence microscopy, immunoblotting, and gene expression, we tested senescence markers in human hepatocytes subjected to chronic hyperinsulinemia in vitro and validated the data in vivo by using liver-specific insulin receptor knockout (LIRKO) mice. The consequences of hyperinsulinemia were also studied in senescent hepatocytes following doxorubicin as a model of stress-induced senescence. Furthermore, the effects of senolytic agents in insulin- and doxorubicin-treated cells were analyzed. Results: Results showed that exposing the hepatocytes to prolonged hyperinsulinemia promotes the onset of senescence by increasing the expression of p53 and p21. It also further enhanced the senescent phenotype in already senescent hepatocytes. Addition of insulin signaling pathway inhibitors prevented the increase in cell senescence, supporting the direct contribution of insulin. Furthermore, LIRKO mice, in which insulin signaling in the liver is abolished due to deletion of the insulin receptor gene, showed no differences in senescence compared to their wild-type counterparts despite having marked hyperinsulinemia indicating these are receptor-mediated effects. In contrast, the persistent hyperinsulinemia in LIRKO mice enhanced senescence in white adipose tissue. In vitro, senolytic agents dasatinib and quercetin reduced the prosenescent effects of hyperinsulinemia in hepatocytes. Conclusion: Our findings demonstrate a direct link between chronic hyperinsulinemia and hepatocyte senescence. This effect can be blocked by reducing the levels of insulin receptors or administration of senolytic drugs, such as dasatinib and quercetin.
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| 9. |
- Braeckman, U., et al.
(author)
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Glacial melt disturbance shifts community metabolism of an Antarctic seafloor ecosystem from net autotrophy to heterotrophy
- 2021
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Journal article (peer-reviewed)abstract
- Climate change-induced glacial melt affects benthic ecosystems along the West Antarctic Peninsula, but current understanding of the effects on benthic primary production and respiration is limited. Here we demonstrate with a series of in situ community metabolism measurements that climate-related glacial melt disturbance shifts benthic communities from net autotrophy to heterotrophy. With little glacial melt disturbance (during cold El Nino spring 2015), clear waters enabled high benthic microalgal production, resulting in net autotrophic benthic communities. In contrast, water column turbidity caused by increased glacial melt run-off (summer 2015 and warm La Nina spring 2016) limited benthic microalgal production and turned the benthic communities net heterotrophic. Ongoing accelerations in glacial melt and run-off may steer shallow Antarctic seafloor ecosystems towards net heterotrophy, altering the metabolic balance of benthic communities and potentially impacting the carbon balance and food webs at the Antarctic seafloor. Ulrike Braeckman et al. use in situ benthic community and benthic biogeochemistry measurements in Potter Cove on the Antarctic Peninsula to show that climate-related glacial melt disturbance shifts benthic communities from net autotrophy to heterotrophy. This study sheds light on how future glacial melt and run-off may affect the metabolic balance of Antarctic benthic communities.
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| 10. |
- 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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| 11. |
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| 12. |
- Ligowski, R., et al.
(author)
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Rhoicosphenia michali: a new species of marine diatom (Bacillariophyta) from King George Island, Antarctica
- 2014
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In: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 191:1, s. 141-153
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Journal article (peer-reviewed)abstract
- Rhoicosphenia michali sp. nov., described from the shallow sublittoral zone in Antarctica, is the second species in the genus with just one raphe slit on its convex valve. The first species, Rhoicosphenia flexa, was also described from marine coastal habitats in the Southern Hemisphere. Here, the morphology and ecology of R. flexa and R. michali are compared. The new species described herein may be endemic to Antarctica and can be found as free living cells on the shallow seabed, although it mainly occurs on the red alga Georgiella confluens, which is endemic to Antarctica.
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| 13. |
- 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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| 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. |
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| 16. |
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| 17. |
- Aarrestad, Thea, et al.
(author)
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Benchmark data and model independent event classification for the large hadron collider
- 2022
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In: SciPost Physics. - 2542-4653. ; 12:1
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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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| 18. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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Fallacia fawensis sp. nov., a new brackish water diatom (Bacillariophyceae) from Southern Iraq
- 2022
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In: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 550:1, s. 71-78
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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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| 19. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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Gomphonemopsis ligowskii, a new diatom (Bacillariophyceae) from the marine Antarctic and a comparison to other Gomphonemopsis
- 2018
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In: Diatom Research. - : Informa UK Limited. - 0269-249X .- 2159-8347. ; 33:1, s. 97-103
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Journal article (peer-reviewed)abstract
- A new marine diatom, Gomphonemopsis ligowskii, is described. Gomphonemopsis ligowskii was found as an epiphyte on the brown macrophyte, Desmarestia anceps, collected from King George Island, Antarctica in January 2016. This species is the first of the genus described from a polar region. It is a small and relatively rare taxon that is characterized by its unique shape and the presence of uniseriate striae, composed of round poroidal areolae on its valve face. The striae are arranged in parallel rows on either side of the axial area, and a row of rounded areolae on both sides of the valve mantle is confined to the wider part of the valve (headpole). A description of valve ultrastructure as well as a comparison with related taxa are provided.
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| 20. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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- Nitzschia biundulata sp. Nov. a new sea ice diatom (bacillariophyceae) from the ross sea, Antarctica
- 2019
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In: Nova Hedwigia: Zeitschrift für Kryptogamenkunde. - : Schweizerbart. - 0029-5035. ; 108:3-4
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Journal article (peer-reviewed)abstract
- - A new marine diatom species, Nitzschia biundulata is described. This species was collected and isolated from the ice cover in the Amundsen Sea, Antarctica during the Austral summer, 2011. The description is based on light and scanning electron microscopes examination as well as molecular analysis including 18S SSU rRNA and rbcL. Morphologically, N. biundulata is characterized by having two extensions of the valve margin in a form of two unequal undulations that are not seen in other taxa of the genus. Molecular sequence data indicated similarity with several Nitzschia species such as Nitzschia apiculata, N. palea, N. capitellata as well as Bacillaria paxillifer. Interestingly, large similarity was found with endosymbiont diatom associated with the dinophyte Peridinium balticum. A comparison with the most related species is provided. © 2019 J. Cramer in Gebrüder Borntraeger Verlagsbuchhandlung, Stuttgart, Germany.
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| 21. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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Two new marine species of Cocconeis (Bacillariophyceae) from the west coast of Sweden
- 2019
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In: European Journal of Taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 497, s. 1-16
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Journal article (peer-reviewed)abstract
- This paper is part of a project of studying benthic diatom biodiversity on marine coastal regions of Sweden with focus on rare and less known species. Two new species of Cocconeis Ehrenb. are described from Vrango, a small island in the west coast of Sweden. Both species were found as epiphytic on the green alga Ulva intestinalis L. Cocconeis magnoareolata Al-Handal, Riaux-Gob., R.Jahn & A.K.Wulff sp. nov. is a small species not exceeding 9 mu m in length and characterized by having large subquadrangular areolae on the sternum valve. Cocconeis vrangoensis Al-Handal & Riaux-Gob. sp. nov. appears similar to some taxa of the 'Cocconeis scutellum complex', but differs by its stria density on both valves and variable features of the areola and valvocopula ultrastructure. Detailed descriptions based on light and electron microscopy examination, a comparison with closely related taxa, as well as a description of the habitat of both species are here presented.
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| 22. |
- Benfeitas, Rui, et al.
(author)
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Characterization of heterogeneous redox responses in hepatocellular carcinoma patients using network analysis
- 2019
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 40, s. 471-487
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Journal article (peer-reviewed)abstract
- Background: Redox metabolism is often considered a potential target for cancer treatment, but a systematic examination of redox responses in hepatocellular carcinoma (HCC) is missing. Methods: Here, we employed systems biology and biological network analyses to reveal key roles of genes associated with redox metabolism in HCC by integrating multi-omics data. Findings: We found that several redox genes, including 25 novel potential prognostic genes, are significantly co-expressed with liver-specific genes and genes associated with immunity and inflammation. Based on an integrative analysis, we found that HCC tumors display antagonistic behaviors in redox responses. The two HCC groups are associated with altered fatty acid, amino acid, drug and hormone metabolism, differentiation, proliferation, and NADPH-independent vs - dependent antioxidant defenses. Redox behavior varies with known tumor subtypes and progression, affecting patient survival. These antagonistic responses are also displayed at the protein and metabolite level and were validated in several independent cohorts. We finally showed the differential redox behavior using mice transcriptomics in HCC and noncancerous tissues and associated with hypoxic features of the two redox gene groups. Interpretation: Our integrative approaches highlighted mechanistic differences among tumors and allowed the identification of a survival signature and several potential therapeutic targets for the treatment of HCC.
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| 23. |
- Björnson, Elias, 1988, et al.
(author)
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Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
- 2015
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 13:9, s. 2014-2026
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Journal article (peer-reviewed)abstract
- Hepatocellular carcinoma (HCC) is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM) for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB) and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1) in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.
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| 24. |
- Bosley, J. R., et al.
(author)
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Informing Pharmacokinetic Models With Physiological Data: Oral Population Modeling of L-Serine in Humans
- 2021
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12
-
Journal article (peer-reviewed)abstract
- To determine how to set optimal oral L-serine (serine) dose levels for a clinical trial, existing literature was surveyed. Data sufficient to set the dose was inadequate, and so an (n = 10) phase I-A calibration trial was performed, administering serine with and without other oral agents. We analyzed the trial and the literature data using pharmacokinetic (PK) modeling and statistical analysis. The therapeutic goal is to modulate specific serine-related metabolic pathways in the liver using the lowest possible dose which gives the desired effect since the upper bound was expected to be limited by toxicity. A standard PK approach, in which a common model structure was selected using a fit to data, yielded a model with a single central compartment corresponding to plasma, clearance from that compartment, and an endogenous source of serine. To improve conditioning, a parametric structure was changed to estimate ratios (bioavailability over volume, for example). Model fit quality was improved and the uncertainty in estimated parameters was reduced. Because of the particular interest in the fate of serine, the model was used to estimate whether serine is consumed in the gut, absorbed by the liver, or entered the blood in either a free state, or in a protein- or tissue-bound state that is not measured by our assay. The PK model structure was set up to represent relevant physiology, and this quantitative systems biology approach allowed a broader set of physiological data to be used to narrow parameter and prediction confidence intervals, and to better understand the biological meaning of the data. The model results allowed us to determine the optimal human dose for future trials, including a trial design component including IV and tracer studies. A key contribution is that we were able to use human physiological data from the literature to inform the PK model and to set reasonable bounds on parameters, and to improve model conditioning. Leveraging literature data produced a more predictive, useful model.
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| 25. |
- Cao, Junyue, et al.
(author)
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Principles of Systems Biology, No. 21
- 2017
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In: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 5:3, s. 158-160
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Journal article (other academic/artistic)abstract
- This month: relating single cells to populations (Cao/Packer, Wu/Altschuler, O'Brien, Friedman), an excess of ribosomes (Barkai), human pathology atlas (Uhlen), signatures of feedback (Rahi), and major genome redesign (Baumgart).
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| 26. |
- Cao, Junyue, et al.
(author)
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Principles of Systems Biology, No. 21 : Editorial
- 2017
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In: CELL SYSTEMS. - : Elsevier BV. - 2405-4712. ; 5:3, s. 158-160
-
Journal article (other academic/artistic)abstract
- This month: relating single cells to populations (Cao/Packer, Wu/Altschuler, O'Brien, Friedman), an excess of ribosomes (Barkai), human pathology atlas (Uhlen), signatures of feedback (Rahi), and major genome redesign (Baumgart).
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| 27. |
- Casey, John R., et al.
(author)
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Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus
- 2016
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In: mSystems. - : AMER SOC MICROBIOLOGY. - 2379-5077. ; 1:6
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Journal article (peer-reviewed)abstract
- Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794 reactions involving 680 metabolites distributed in 6 subcellular locations. iJC568 was used to quantify metabolic fluxes under PLG conditions, and we observed a close correspondence between experimental and computed fluxes. We found that MED4 has minimized its dependence on intracellular phosphate, not only through drastic depletion of phosphorus-containing biomass components but also through network-wide reductions in phosphate-reaction participation and the loss of a key enzyme, succinate dehydrogenase. These alterations occur despite the stringency of having relatively few pathway redundancies and an extremely high proportion of essential metabolic genes (47%; defined as the percentage of lethal in silico gene knockouts). These strategies are examples of nutrient-controlled adaptive evolution and confer a dramatic growth rate advantage to MED4 in phosphorus-limited regions. IMPORTANCE Microbes are known to employ three basic strategies to compete for limiting elemental resources: (i) cell quotas may be adjusted by alterations to cell physiology or by substitution of a more plentiful resource, (ii) stressed cells may synthesize high-affinity transporters, and (iii) cells may access more costly sources from internal stores, by degradation, or by petitioning other microbes. In the case of phosphorus, a limiting resource in vast oceanic regions, the cosmopolitan cyanobacterium Prochlorococcus marinus thrives by adopting all three strategies and a fourth, previously unknown strategy. By generating a detailed model of its metabolism, we found that strain MED4 has evolved a way to reduce its dependence on phosphate by minimizing the number of enzymes involved in phosphate transformations, despite the stringency of nearly half of its metabolic genes being essential for survival. Relieving phosphorus limitation, both physiologically and throughout intermediate metabolism, substantially improves phosphorus-specific growth rates.
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| 28. |
- Emanuelsson, Eric B., et al.
(author)
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MRI characterization of skeletal muscle size and fatty infiltration in long--term trained and untrained individuals
- 2022
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In: Physiological Reports. - : Wiley. - 2051-817X. ; 54:9, s. 389-389
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Journal article (peer-reviewed)abstract
- This study investigated body composition measures in highly trained and untrained individuals using whole--body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.
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| 29. |
- 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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| 30. |
- Hambsch, F. -J, et al.
(author)
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Investigation of the Fission Process at IRMM
- 2011
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In: Journal of the Korean Physical Society. - : Korean Physical Society. - 0374-4884 .- 1976-8524. ; 59:2, s. 1654-1659
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Journal article (peer-reviewed)abstract
- The investigation of the fission process is and has been a major undertaking at IRMM. The most recent investigations concerned the reaction (234)U(n,f) and (238)U(n,f) around vibrational resonances at the barrier of the fission cross-section. Furthermore prompt neutron emission of (252)Cf(SF) has been investigated understanding for the first time the prompt neutron multiplicity as a function of total kinetic energy (TKE). Theoretical modelling of reaction cross sections as well as prompt neutron multiplicity and spectra has been performed using the experimental data as input parameters. Also instrument developments for correlation measurements of fission fragment properties has been pursued in recent years with the time-of-flight spectrometer VERDI and detectors for prompt fission gamma-ray.
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| 31. |
- Harms, M. J., et al.
(author)
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Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes
- 2019
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 27:1
-
Journal article (peer-reviewed)abstract
- White adipose tissue (WAT) is a central factor in the development of type 2 diabetes, but there is a paucity of translational models to study mature adipocytes. We describe a method for the culture of mature white adipocytes under a permeable membrane. Compared to existing culture methods, MAAC (membrane mature adipocyte aggregate cultures) better maintain adipogenic gene expression, do not dedifferentiate, display reduced hypoxia, and remain functional after long-term culture. Subcutaneous and visceral adipocytes cultured as MAAC retain depot-specific gene expression, and adipocytes from both lean and obese patients can be cultured. Importantly, we show that rosiglitazone treatment or PGC1 alpha overexpression in mature white adipocytes induces a brown fat transcriptional program, providing direct evidence that human adipocytes can transdifferentiate into brown-like adipocytes. Together, these data show that MAAC are a versatile tool for studying phenotypic changes of mature adipocytes and provide an improved translational model for drug development.
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| 32. |
- Hoffmann, R., et al.
(author)
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Implications of Glacial Melt-Related Processes on the Potential Primary Production of a Microphytobenthic Community in Potter Cove (Antarctica)
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:October
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Journal article (peer-reviewed)abstract
- The Antarctic Peninsula experiences a fast retreat of glaciers, which results in an increased release of particles and sedimentation and, thus, a decrease in the available photosynthetic active radiation (PAR, 400-700 nm) for benthic primary production. In this study, we investigated how changes in the general sedimentation and shading patterns affect the primary production by benthic microalgae, the microphytobenthos. In order to determine potential net primary production and respiration of the microphytobenthic community, sediment cores from locations exposed to different sedimentation rates and shading were exposed to PAR of 0-70 mu.mol photons m(-2)s(-1). Total oxygen exchange rates and microphytobenthic diatom community structure, density, and biomass were determined. Our study revealed that while the microphytobenthic diatom density and composition remained similar, the net primary production of the microphytobenthos decreased with increasing sedimentation and shading. By comparing our experimental results with in situ measured PAR intensities, we furthermore identified microphytobenthic primary production as an important carbon source within Potter Cove's benthic ecosystem. We propose that the microphytobenthic contribution to the total primary production may drop drastically due to Antarctic glacial retreat and related sedimentation and shading, with yet unknown consequences for the benthic heterotrophic community, its structure, and diversity.
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| 33. |
- Küçükdoğru, R., et al.
(author)
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Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis
- 2020
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In: Metabolic brain disease. - : Springer. - 0885-7490 .- 1573-7365.
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Journal article (peer-reviewed)abstract
- Parkinson’s disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP+) in experimental PD model. Experimental PD model was constituted by application of MPP+ to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP+ toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP+ on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP+ application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP+ induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP+ toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.
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| 34. |
- Lee, SangWook, et al.
(author)
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Network analyses identify liver-specific targets for treating liver diseases
- 2017
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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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| 35. |
- 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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| 36. |
- Mardinoglu, Adil, et al.
(author)
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Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue
- 2015
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Journal article (peer-reviewed)abstract
- Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 +/- 2 months. Global gene expression differences in VAT and subcutaneous (S) AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.
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| 37. |
- Mikaeloff, Flora, et al.
(author)
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Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection
- 2023
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In: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 12
-
Journal article (peer-reviewed)abstract
- Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1-3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4(+) T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower alpha-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.
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| 38. |
- Pettersen, Emily, 1996, et al.
(author)
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Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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In: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS. - 1940-087X. ; :205
-
Journal article (peer-reviewed)abstract
- Surgical procedures, including nerve reconstruction and end -organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.
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| 39. |
- Pettersen, Emily, 1996, et al.
(author)
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Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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In: Journal of Visualized Experiments. - 1940-087X. ; 2024:205
-
Journal article (peer-reviewed)abstract
- Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement-targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.
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| 40. |
- 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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| 41. |
- 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
-
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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| 42. |
- Yulug, B., et al.
(author)
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Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
- 2023
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In: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 12:1
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Journal article (peer-reviewed)abstract
- Background Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
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