| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Andersen, Casper W., et al.
(författare)
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OPTIMADE, an API for exchanging materials data
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification.
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| 3. |
- Bosque, Irene, et al.
(författare)
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Redox Catalysis Facilitates Lignin Depolymerization
- 2017
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7951 .- 2374-7943. ; 3:6, s. 621-628
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Tidskriftsartikel (refereegranskat)abstract
- Lignin is a recalcitrant and underexploited natural feedstock for aromatic commodity chemicals, and its degradation generally requires the use of high temperatures and harsh reaction conditions. Herein we present an ambient temperature one-pot process for the controlled oxidation and depolymerization of this potent resource. Harnessing the potential of electrocatalytic oxidation in conjugation with our photocatalytic cleavage methodology, we have developed an operationally simple procedure for selective fragmentation of β-O-4 bonds with excellent mass recovery, which provides a unique opportunity to expand the existing lignin usage from energy source to commodity chemicals and synthetic building block source.
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| 4. |
- Dinér, Peter, 1976, et al.
(författare)
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Design, synthesis, and characterization of a highly effective Hog1 inhibitor: a powerful tool for analyzing MAP kinase signaling in yeast.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- The Saccharomyces cerevisiae High-Osmolarity Glycerol (HOG) pathway is a conserved mitogen-activated protein kinase (MAPK) signal transduction system that often serves as a model to analyze systems level properties of MAPK signaling. Hog1, the MAPK of the HOG-pathway, can be activated by various environmental cues and it controls transcription, translation, transport, and cell cycle adaptations in response to stress conditions. A powerful means to study signaling in living cells is to use kinase inhibitors; however, no inhibitor targeting wild-type Hog1 exists to date. Herein, we describe the design, synthesis, and biological application of small molecule inhibitors that are cell-permeable, fast-acting, and highly efficient against wild-type Hog1. These compounds are potent inhibitors of Hog1 kinase activity both in vitro and in vivo. Next, we use these novel inhibitors to pinpoint the time of Hog1 action during recovery from G(1) checkpoint arrest, providing further evidence for a specific role of Hog1 in regulating cell cycle resumption during arsenite stress. Hence, we describe a novel tool for chemical genetic analysis of MAPK signaling and provide novel insights into Hog1 action.
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| 5. |
- Ganna, Andrea, et al.
(författare)
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Large-scale non-targeted metabolomic profiling in three human population-based studies
- 2016
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Non-targeted metabolomic profiling is used to simultaneously assess a large part of the metabolome in a biological sample. Here, we describe both the analytical and computational methods used to analyze a large UPLC–Q-TOF MS-based metabolomic profiling effort using plasma and serum samples from participants in three Swedish population-based studies of middle-aged and older human subjects: TwinGene, ULSAM and PIVUS. At present, more than 200 metabolites have been manually annotated in more than 3600 participants using an in-house library of standards and publically available spectral databases. Data available at the metabolights repository include individual raw unprocessed data, processed data, basic demographic variables and spectra of annotated metabolites. Additional phenotypical and genetic data is available upon request to cohort steering committees. These studies represent a unique resource to explore and evaluate how metabolic variability across individuals affects human diseases.
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| 6. |
- Kärkäs, Markus D., et al.
(författare)
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Enchained by Visible Light–Mediated Photoredox Catalysis
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 349:6254, s. 1285-1286
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals are exploited in biology, often through highly controlled enzymatic reactions, to drive many reactions that would be difficult via nonradical routes that transfer two electrons (1). In synthetic chemistry, visible-light photoredox catalysis has emerged as an economical and environmentally benign route for promoting free radical transformations in the lab (2–4). Although the initial light-sensitization steps are well established (5), insufficient attention has been dedicated to essential mechanistic features of the closed catalytic cycle (6). Several reports have hypothesized that these photocatalyzed reactions are terminated through a closed catalytic cycle, which delivers the final product and regenerates the ground state of the photosensitizer (PS). However, Cismesia and Yoon (6) highlight that some of the mechanistic proposals may be incomplete and may involve radical chains.
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| 7. |
- Kärkäs, Markus D., et al.
(författare)
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Photocatalytic Oxidation of Lignin Model Systems by Merging Visible-Light Photoredox and Palladium Catalysis
- 2016
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 18:19, s. 5166-5169
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Tidskriftsartikel (refereegranskat)abstract
- Lignin valorization has long been recognized as a sustainable solution for the renewable production of aromatic compounds. Two-step oxidation/reduction strategies, whereby the first oxidation step is required to “activate” lignin systems for controlled fragmentation reactions, have recently emerged as viable routes toward this goal. Herein we describe a catalytic protocol for oxidation of lignin model systems by combining photoredox and Pd catalysis. The developed dual catalytic protocol allowed the efficient oxidation of lignin model substrates at room temperature to afford the oxidized products in good to excellent yields.
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| 8. |
- Kärkäs, Markus D., et al.
(författare)
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Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis
- 2016
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Ingår i: Chemical Reviews. - : American Chemical Society (ACS). - 0009-2665 .- 1520-6890. ; 116:17, s. 9683-9747
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Forskningsöversikt (refereegranskat)abstract
- The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.
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| 9. |
- Kärkäs, Markus D., et al.
(författare)
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Transition-Metal Catalyzed Valorization of Lignin: The Key to a Sustainable Carbon-Neutral Future
- 2016
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Ingår i: Organic and biomolecular chemistry. - : RSC Publishing. - 1477-0520 .- 1477-0539. ; 14:6, s. 1853-1914
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Forskningsöversikt (refereegranskat)abstract
- The development of a sustainable, carbon-neutral biorefinery has emerged as a prominent scientific and engineering goal of the 21st century. As petroleum has become less accessible, biomass-based carbon sources have been investigated for utility in fuel production and commodity chemical manufacturing. One underutilized biomaterial is lignin; however, its highly crosslinked and randomly polymerized composition have rendered this biopolymer recalcitrant to existing chemical processing. More recently, insight into lignin's molecular structure has reinvigorated chemists to develop catalytic methods for lignin depolymerization. This review examines the development of transition-metal catalyzed reactions and the insights shared between the homogeneous and heterogeneous catalytic systems towards the ultimate goal of valorizing lignin to produce value-added products.
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| 10. |
- Loh, Tze Ping, et al.
(författare)
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The LEAP checklist for Laboratory Evaluation and Analytical Performance Characteristics reporting of clinical measurement procedures
- 2023
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 83:7, s. 467-469
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Tidskriftsartikel (refereegranskat)abstract
- Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript.The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.
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