| 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. |
- Baeten, Lander, et al.
(författare)
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Identifying the tree species compositions that maximize ecosystem functioning in European forests
- 2019
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Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 56:3, s. 733-744
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Tidskriftsartikel (refereegranskat)abstract
- 1. Forest ecosystem functioning generally benefits from higher tree species richness, but variation within richness levels is typically large. This is mostly due to the contrasting performances of communities with different compositions. Evidence-based understanding of composition effects on forest productivity, as well as on multiple other functions will enable forest managers to focus on the selection of species that maximize functioning, rather than on diversity per se.2. We used a dataset of 30 ecosystem functions measured in stands with different species richness and composition in six European forest types. First, we quantified whether the compositions that maximize annual above-ground wood production (productivity) generally also fulfil the multiple other ecosystem functions (multifunctionality). Then, we quantified the species identity effects and strength of interspecific interactions to identify the "best" and "worst" species composition for multifunctionality. Finally, we evaluated the real-world frequency of occurrence of best and worst mixtures, using harmonized data from multiple national forest inventories.3. The most productive tree species combinations also tended to express relatively high multifunctionality, although we found a relatively wide range of compositions with high- or low-average multifunctionality for the same level of productivity. Monocultures were distributed among the highest as well as the lowest performing compositions. The variation in functioning between compositions was generally driven by differences in the performance of the component species and, to a lesser extent, by particular interspecific interactions. Finally, we found that the most frequent species compositions in inventory data were monospecific stands and that the most common compositions showed below-average multifunctionality and productivity.4. Synthesis and applications. Species identity and composition effects are essential to the development of high-performing production systems, for instance in forestry and agriculture. They therefore deserve great attention in the analysis and design of functional biodiversity studies if the aim is to inform ecosystem management. A management focus on tree productivity does not necessarily trade-off against other ecosystem functions; high productivity and multifunctionality can be combined with an informed selection of tree species and species combinations.
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| 3. |
- Hippe, Andreas, et al.
(författare)
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EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.
- 2020
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 123:6, s. 942-954
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.METHODS: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.RESULTS: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.CONCLUSION: We propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.
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| 4. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 6. |
- Thalhammer, Julian, et al.
(författare)
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Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations.
- 2021
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825.
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Tidskriftsartikel (refereegranskat)abstract
- Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.
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| 7. |
- Akinsinde, Lewis O., et al.
(författare)
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Surface characterization and resistance changes of silver-nanowire networks upon atmospheric plasma treatment
- 2021
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 550
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Tidskriftsartikel (refereegranskat)abstract
- Highly conductive silver-nanowire (Ag-NW) networks are used in composite materials as conductive channels. Their resistance tuning can be accomplished by changing the Ag-NW concentration, and, therefore, changing the network structure. In this study, an alternative pathway to resistance engineering of conductive Ag-NW networks by local atmospheric plasma treatment is employed. The corresponding changes in nanowire network morphology and crystallinity as a function of plasma etching time are investigated by time-resolved grazingincidence X-ray scattering, field-effect scanning electron microscopy, and X-ray photoelectron spectroscopy. Three characteristic etching phases are identified. The first two phases enable the controlled engineering of the electrical properties with different rates of resistance change, which results from changes in nanowire shape, network morphology, and different oxidation rates. Phase III is characterized by pronounced fragmentation and destruction of the Ag-NW networks. These results show the feasibility of atmospheric plasma treatments to tune the local electrical properties of conductive Ag-NW networks. Furthermore, we present a physical Monte Carlo model explaining the electrical network properties as a function of plasma etching time based on the network connectivity and a constant plasma etching rate of 570 ng s-1 cm-2.
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| 8. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 9. |
- Beyerlein, Kenneth R., et al.
(författare)
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Mix-and-diffuse serial synchrotron crystallography
- 2017
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Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4:6, s. 769-777
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Tidskriftsartikel (refereegranskat)abstract
- Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.
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| 10. |
- Bieron, Jacek, et al.
(författare)
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Ab initio MCDHF calculations of electron-nucleus interactions
- 2015
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Ingår i: Physica Scripta. - : Institute of Physics Publishing (IOPP). - 0031-8949 .- 1402-4896. ; 90:5
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Tidskriftsartikel (refereegranskat)abstract
- We present recent advances in the development of atomic ab initio multiconfiguration Dirac– Hartree–Fock theory, implemented in the GRASP relativistic atomic structure code. For neutral atoms, the deviations of properties calculated within the Dirac–Hartree–Fock (DHF) method (based on independent particle model of an atomic cloud) are usually dominated by electron correlation effects, i.e. the non-central interactions of individual electrons. We present the recent advances in accurate calculations of electron correlation effects in small, medium, and heavy neutral atoms. We describe methods of systematic development of multiconfiguration expansions leading to systematic, controlled improvement of the accuracy of the ab initio calculations. These methods originate from the concept of the complete active space (CAS) model within the DHF theory, which, at least in principle, permits fully relativistic calculations with full account of electron correlation effects. The calculations within the CAS model on currently available computer systems are feasible only for very light systems. For heavier atoms or ions with more than a few electrons, restrictions have to be imposed on the multiconfiguration expansions. We present methods and tools, which are designed to extend the numerical calculations in a controlled manner, where multiconfiguration expansions account for all leading electron correlation effects. We show examples of applications of the GRASP code to calculations of hyperfine structure constants, but the code may be used for calculations of arbitrary bound-state atomic properties. In recent years it has been applied to calculations of atomic and ionic spectra (transition energies and rates), to determinations of nuclear electromagnetic moments, as well as to calculations related to interactions of bound electrons with nuclear electromagnetic moments leading to violations of discrete symmetries.
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