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Sökning: WFRF:(Niklas Karl J.)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Jones, Benedict C, et al. (författare)
  • To which world regions does the valence-dominance model of social perception apply?
  • 2021
  • Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
  • Tidskriftsartikel (refereegranskat)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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3.
  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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4.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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5.
  • Reyes, Sebastián C, et al. (författare)
  • PFG NMR self-diffusion of small hydrocarbons in high silica DDR, CHA and LTA structures
  • 2008
  • Ingår i: Microporous and Mesoporous Materials. - : Elsevier BV. - 1387-1811. ; 109, s. 327-334
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) spectroscopy was used to measure and rationalize the intracrystalline self-diffusion coefficients of small hydrocarbons in high silica DDR (ZSM-58, Si/Al = 190), pure silica chabazite (Si-CHA) and ITQ-29 (Si-LTA) structures. The self-diffusivities of methane, ethane, ethylene and propylene were measured on these materials at 301 K and 101.3 kPa. A clear correlation is shown between the size of the 8-ring windows and the size of the molecules on the measured self-diffusivities. Window sizes were obtained from X-ray diffraction measurements: [3.65 × 4.38 Å] for ZSM-58, [3.70 × 4.17 Å] for Si-CHA and [4.00 × 4.22 Å] for Si-LTA. An increase in self-diffusivity with window size and a decrease with molecular size were clearly observed. The magnitudes of these effects are shown to be very large. For example, at 301 K and 101.3 kPa, the self-diffusivities of methane were 1.6 × 10−8 cm2/s, 10.7 × 10−8 cm2/s and 142.0 × 10−8 cm2/s in ZSM-58, Si-CHA and Si-LTA, respectively; an increase in self-diffusivity of nearly 2 orders of magnitude that is primarily due to window size effects. Similarly, at 301 K and 101.3 kPa, the self-diffusivities of methane, ethylene, ethane and propylene in Si-LTA were 142.0 × 10−8 cm2/s, 21.4 × 10−8 cm2/s, 20.9 × 10−8 cm2/s and 0.0047 × 10−8 cm2/s, respectively; a decrease in self-diffusivity with molecular size of more than 4 orders of magnitude. These findings contribute to a fundamental understanding of self-diffusion in microporous materials and have important implications for kinetic based separation schemes in which diffusion plays a key role.
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6.
  • Bolinder, Kristina, et al. (författare)
  • AERODYNAMICS AND POLLEN ULTRASTRUCTURE IN EPHEDRA
  • 2015
  • Ingår i: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 102:3, s. 457-470
  • Tidskriftsartikel (refereegranskat)abstract
    • Premise of the study: Pollen dispersal is affected by the terminal settling velocity (U-t) of the grains, which is determined by their size, bulk density, and by atmospheric conditions. The likelihood that wind-dispersed pollen is captured by ovulate organs is influenced by the aerodynamic environment created around and by ovulate organs. We investigated pollen ultrastructure and U-t of Ephedra foeminea (purported to be entomophilous), and simulated the capture efficiency of its ovules. Results were compared with those from previously studied anemophilous Ephedra species. Methods: U-t was determined using stroboscopic photography of pollen in free fall. The acceleration field around an average ovule was calculated, and inflight behavior of pollen grains was predicted using computer simulations. Pollen morphology and ultrastructure were investigated using SEM and STEM. Key results: Pollen wall ultrastructure was correlated with U-t in Ephedra. The relative proportion and amount of granules in the infratectum determine pollen bulk densities, and (together with overall size) determine U-t and thus dispersal capability. Computer simulations failed to reveal any functional traits favoring anemophilous pollen capture in E. foeminea. Conclusion: The fast U-t and dense ultrastructure of E. foeminea pollen are consistent with functional traits that distinguish entomophilous species from anemophilous species. In anemophilous Ephedra species, ovulate organs create an aerodynamic microenvironment that directs airborne pollen to the pollination drops. In E. foeminea, no such microenvironment is created. Ephedroid palynomorphs from the Cretaceous share the ultrastructural characteristics of E. foeminea, and at least some may, therefore, have been produced by insect-pollinated plants.
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7.
  • Bomark, Niklas, 1984-, et al. (författare)
  • Corporate Demography and Income Inequality : Revisited
  • 2019
  • Ingår i: Academy of Management Annual Meeting Proceedings. - New York : Academy of Management. - 0065-0668 .- 2151-6561. ; :1
  • Tidskriftsartikel (refereegranskat)abstract
    • We replicate and extend Sorenson and Sorensen’s (2007) study how corporate demography shapes workforce wage inequality across region-industries by: (i) replicating their original results from Danish regions in 1992-1998 using a close to identical dataset of industry-regions in neighboring Sweden during the same time-period, (ii) extending the study to 2012 to gauge the corporate demography – wage inequality relationship during a period of rapidly increasing inequality, and (iii) expanding the scope of the model by two new measures of organizational form diversity. Our findings suggest a fairly strong test-retest validity, an enhanced effect of corporate demography over time, but that more nuanced measure of organization form diversity do not necessarily enhance the model’s explanatory power.
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8.
  • Djupedal, Ingela, et al. (författare)
  • Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA
  • 2009
  • Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 28:24, s. 3832-3844
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of heterochromatin at the centromeres in fission yeast depends on transcription of the outer repeats. These transcripts are processed into siRNAs that target homologous loci for heterochromatin formation. Here, high throughput sequencing of small RNA provides a comprehensive analysis of centromere-derived small RNAs. We found that the centromeric small RNAs are Dcr1 dependent, carry 50-monophosphates and are associated with Ago1. The majority of centromeric small RNAs originate from two remarkably well-conserved sequences that are present in all centromeres. The high degree of similarity suggests that this non-coding sequence in itself may be of importance. Consistent with this, secondary structure-probing experiments indicate that this centromeric RNA is partially double-stranded and is processed by Dicer in vitro. We further demonstrate the existence of small centromeric RNA in rdp1D cells. Our data suggest a pathway for siRNA generation that is distinct from the well-documented model involving RITS/RDRC. We propose that primary transcripts fold into hairpin-like structures that may be processed by Dcr1 into siRNAs, and that these siRNAs may initiate heterochromatin formation independent of RDRC activity. The EMBO Journal (2009) 28, 3832-3844. doi: 10.1038/emboj.2009.351; Published online 26 November 2009
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9.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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10.
  • Mårtensson, Ulrika, et al. (författare)
  • Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
  • 2009
  • Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
  • Tidskriftsartikel (refereegranskat)abstract
    • In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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