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1.	Skirgård, Hedvig, et al. (författare) Grambank reveals the importance of genealogical constraints on linguistic diversity and highlights the impact of language loss. Science Advances 2023 Ingår i: Science Advances. ; 9:16:eadg6175, s. 1-15 Tidskriftsartikel (refereegranskat)
2.	Kanoni, Stavroula, et al. (författare) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
3.	Wessel, Jennifer, et al. (författare) Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility 2015 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6 Tidskriftsartikel (refereegranskat)abstract Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
4.	Kanai, M, et al. (författare) 2023 swepub:Mat__t
5.	Rafnar, Thorunn, et al. (författare) European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene. 2011 Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81 Tidskriftsartikel (refereegranskat)abstract Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
6.	Niemi, MEK, et al. (författare) 2021 swepub:Mat__t
7.	Albers, Roland, et al. (författare) Magnetospheric Venus Space Explorers (MVSE) mission : a proposal for understanding the dynamics of induced magnetospheres 2024 Ingår i: Acta Astronautica. - : Elsevier. - 0094-5765 .- 1879-2030. ; 221, s. 194-205 Tidskriftsartikel (refereegranskat)abstract Induced magnetospheres form around planetary bodies with atmospheres through the interaction of the solar wind with their ionosphere. Induced magnetospheres are highly dependent on the solar wind conditions and have only been studied with single spacecraft missions in the past. Without simultaneous measurements of solar wind variations and phenomena in the magnetosphere, establishing a link between both can only be done indirectly, using statistics over a large set of measurements. This gap in knowledge could be addressed by a multi-spacecraft plasma mission, optimized for studying global spatial and temporal variations in the magnetospheric system around Venus, which hosts the most prominent example of an induced magnetosphere in our solar system. The MVSE mission comprises four satellites, of which three are identical scientific spacecraft, carrying the same suite of instruments probing different regions of the induced magnetosphere and the solar wind simultaneously. The fourth spacecraft is the transfer vehicle which acts as a relay satellite for communications at Venus. In this way, changes in the solar wind conditions and extreme solar events can be observed, and their effects can be quantified as they propagate through the Venusian induced magnetosphere. Additionally, energy transfer in the Venusian induced magnetosphere can be investigated. The scientific payload includes instrumentation to measure the magnetic field, electric field, and ion–electron velocity distributions. This study presents the scientific motivation for the mission as well as requirements and the resulting mission design. Concretely, a mission timeline along with a complete spacecraft design, including mass, power, communication, propulsion and thermal budgets are given. This mission was initially conceived at the Alpbach Summer School 2022 and refined during a week-long study at ESA's Concurrent Design Facility in Redu, Belgium.
8.	Anderson, Tovi M., et al. (författare) Molecular and Evolutionary History of Melanism in North American Gray Wolves 2009 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 323:5919, s. 1339-1343 Tidskriftsartikel (refereegranskat)abstract Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives.
9.	Bachmann, Radu, et al. (författare) Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism 2022 Ingår i: Cells. - : MDPI. - 2073-4409. ; 11:17 Tidskriftsartikel (refereegranskat)abstract Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.
10.	Backes, Claudia, et al. (författare) Production and processing of graphene and related materials 2020 Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2 Tidskriftsartikel (refereegranskat)abstract We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
11.	Barsh, Gregory S., et al. (författare) How the Gray Wolf Got Its Color - Response 2009 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5936, s. 34-34 Tidskriftsartikel (refereegranskat)
12.	Benatar, Michael, et al. (författare) Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial 2024 Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699 Tidskriftsartikel (refereegranskat)abstract Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
13.	Bergström, Anders, et al. (författare) Grey wolf genomic history reveals a dual ancestry of dogs 2022 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320 Tidskriftsartikel (refereegranskat)abstract The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
14.	Brändén, Gisela, 1975, et al. (författare) Coherent diffractive imaging of microtubules using an X-ray laser. 2019 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1 Tidskriftsartikel (refereegranskat)abstract X-ray free electron lasers (XFELs) create new possibilities for structural studies of biological objects that extend beyond what is possible with synchrotron radiation. Serial femtosecond crystallography has allowed high-resolution structures to be determined from micro-meter sized crystals, whereas single particle coherent X-ray imaging requires development to extend the resolution beyond a few tens of nanometers. Here we describe an intermediate approach: the XFEL imaging of biological assemblies with helical symmetry. We collected X-ray scattering images from samples of microtubules injected across an XFEL beam using a liquid microjet, sorted these images into class averages, merged these data into a diffraction pattern extending to 2nm resolution, and reconstructed these data into a projection image of the microtubule. Details such as the 4nm tubulin monomer became visible in this reconstruction. These results illustrate the potential of single-molecule X-ray imaging of biological assembles with helical symmetry at room temperature.
15.	Deisenroth, David C., et al. (författare) Measurement Uncertainty of Surface Temperature Distributions for Laser Powder Bed Fusion Processes 2021 Ingår i: Journal of research of the National Institute of Standards and Technology. - : NATL INST STANDARDS & TECHNOLOGY-NIST. - 1044-677X .- 2165-7254. ; 126 Tidskriftsartikel (refereegranskat)abstract This paper describes advances in measuring the characteristic spatial distribution of surface temperature and emissivity during laser -metal interaction under conditions relevant for laser powder bed fusion (LPBF) additive manufacturing processes. Detailed descriptions of the measurement process, results, and approaches to determining uncertainties are provided. Measurement uncertainties have complex dependencies on multiple process parameters, so the methodology is demonstrated on one set of process parameters and one material. Well-established literature values for high-purity nickel solidification temperature and emissivity at the solidification temperature were used to evaluate the predicted uncertainty of the measurements. The standard temperature measurement uncertainty is found to be approximately 0.9 % of the absolute temperature (16 degrees C), and the standard relative emissivity measurement uncertainty is found to be approximately 8 % at the solidification point of high-purity nickel, both of which are satisfactory. This paper also outlines several potential sources of test uncertainties, which may require additional experimental evaluation. The largest of these are the metal vapor and ejecta that are produced as process by-products, which can potentially affect the imaging quality, reflectometry results, and thermal signature of the process, while also affecting the process of laser power delivery. Furthermore, the current paper focuses strictly on the uncertainties of the emissivity and temperature measurement approach and therefore does not detail a variety of uncertainties associated with experimental controls that must be evaluated for future generation of reference data.
16.	Diaz-Gallo, Lina-Marcela, et al. (författare) Four Systemic Lupus Erythematosus Subgroups, Defined by Autoantibodies Status, Differ Regarding HLA-DRB1 Genotype Associations and Immunological and Clinical Manifestations 2022 Ingår i: ACR Open Rheumatology. - : John Wiley & Sons. - 2578-5745. ; 4:1, s. 27-39 Tidskriftsartikel (refereegranskat)abstract Objective: The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data.Methods: An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjögren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjögren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and β2 glycoprotein I [β2 GPI]-IgG) in 911 patients with SLE from two cohorts. We evaluated whether each SLE subgroup is associated with HLA-DRB1 alleles, clinical manifestations (n = 743), and cytokine levels in circulation (n = 446).Results: Our analysis identified four subgroups among the patients with SLE. Subgroup 1 (29.3%) was dominated by anti-SSA/Ro60/Ro52/SSB autoantibodies and was strongly associated with HLA-DRB103 (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 4.52-4.94). Discoid lesions were more common for this disease subgroup (OR = 1.71, 95% CI = 1.18-2.47). Subgroup 2 (28.7%) was dominated by anti-nucleosome/SmRNP/DNA/RNPA autoantibodies and associated with HLA-DRB115 (OR = 1.62, 95% CI = 1.41-1.84). Nephritis was most common in this subgroup (OR = 1.61, 95% CI = 1.14-2.26). Subgroup 3 (23.8%) was characterized by anti-ß2 GPI-IgG/anti-CL-IgG/IgM autoantibodies and a higher frequency of HLA-DRB1*04 compared with the other patients with SLE. Vascular events were more common in Subgroup 3 (OR = 1.74, 95% CI = 1.2-2.5). Subgroup 4 (18.2%) was negative for the investigated autoantibodies, and this subgroup was not associated with HLA-DRB1. Additionally, the levels of eight cytokines significantly differed among the disease subgroups.Conclusion: Our findings suggest that four fairly distinct subgroups can be identified on the basis of the autoantibody profile in SLE. These four SLE subgroups differ regarding associations with HLA-DRB1 alleles and immunological and clinical features, suggesting dissimilar disease pathways.
17.	Fant, Eric Michael, 1754-1817 (författare) Dissertatio de regiminis formarum periodis, quam, cons. ampl. facult. philos. Upsal. præside doct. Erico M. Fant ... pro laurea publice ventilandam submittit Daniel. Leon. Kinmanson, Ostrogothus. In audit. Gust. Maj. Die XIV Maj. MDCCCVI. H. a. m. s. 1806 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
18.	Fittipaldi, Antonela S., et al. (författare) Ghrelin proteolysis increases in plasma of men, but not women, with obesity 2023 Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 313 Tidskriftsartikel (refereegranskat)abstract Aims: Since plasma ghrelin can undergo des-acylation and proteolysis, the aim of this study was to investigate the extent to which an enhancement of these reactions is associated to the decrease of ghrelin in plasma after food intake or in individuals with obesity.Main methods: we performed an intervention cross-sectional study, in which levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n = 21 males) with normal weight (NW, n = 20) or overweight/obesity (OW/OB, n = 20).Key findings: Preprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was -4.6-fold higher in plasma of males with OW/OB. In males, ghrelin proteolysis positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with OW/OB, but preprandial ghrelin proteolysis was not different between females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially-2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes.Significance: Current study shows that ghrelin proteolysis increases in males with obesity as well as after meal in lean individuals. Therefore, ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.
19.	Fogh, Isabella, et al. (författare) A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis 2014 Ingår i: Human Molecular Genetics. - Oxford : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:8, s. 2220-2231 Tidskriftsartikel (refereegranskat)abstract Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (90) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P 1.11 10(8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P 8.62 10(9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P 7.69 10(9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as 12 using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.
20.	Fogh, Isabella, et al. (författare) Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis 2016 Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:7, s. 812-820 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSIONS AND RELEVANCE This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.
21.	Haller, Daniel G, et al. (författare) Potential regional differences for the tolerability profiles of fluoropyrimidines. 2008 Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:13, s. 2118-23 Tidskriftsartikel (refereegranskat)abstract PURPOSE: We conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability. METHODS: Treatment-related safety data from three phase III clinical studies were analyzed by multivariate analysis: two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study). RESULTS: In the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR. CONCLUSION: Regional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.
22.	Hoshino, Ayuko, et al. (författare) Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers 2020 Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044- Tidskriftsartikel (refereegranskat)abstract There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
23.	Höijer, Benjamin, 1767-1812 (författare) Dissertatio de constructione philosophica, cujus specimen primum ... proponunt mag. Benj. Carol. H. Höijer, ... et Daniel Kinmanson, ... in audit. Gust. Maj. d. VIII maji MDCCXCIX. 1799 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
24.	Inserillo, Daniel R., et al. (författare) Transient Swainson's Thrush (Catharus Ustulatus) Wintering In The Andean Foothills of Ecuador are Almost Exclusively Young Males 2020 Ingår i: Ornitologia Neotropical. - : Neotropical Ornithological Society. - 1075-4377. ; 31, s. 98-105 Tidskriftsartikel (refereegranskat)abstract We know relatively little about the non-breeding period of most migratory birds. Decades of research on Swainson’s Thrush (Catharus ustulatus) has focused on their breeding ecology, whereas their non-breeding ecology is limited to broad patterns of distribution and migratory stop-over ecology. For the nearly 50 years, the US Breeding Bird Survey recorded declines of 0.7% per year for the Russet-backed Swainson’s Thrush (C. u. swainsonii) subspecies, which spends the non-breeding period in South America. However, there is an insufficient understanding of the constraints across their annual cycle to determine reasons for the sustained decline. In 2013 and 2014, we examined their little studied non-breeding period on the Andean slopes of Ecuador where prior experience showed that they were seasonally abundant. Here rapid deforestation threatens primary forest. We used point counts and radio telemetry to evaluate whether primary forest was used preferentially to recently regenerated second-growth forest. From point counts, 76% of detections and almost all captured individuals occurred in secondary forest. Of 86 birds captured in mist nets, 85 were males and 83 young of the year, indicating a highly skewed ratio in favor of young males. Radio telemetry demonstrated preference for secondary forest, especially for fruiting Cecropia spp. trees, with no apparent territorial behavior by those tracked and with short residency times. A marked decrease in density over the course of the field season suggests an itinerant population possibly tracking the ephemeral use of fruit resources. Alternatively, these temporal and spatial patterns could suggest that this population undergoes a mid-winter intratropical migration or at least landscape-level movements. However, we observed thrushes throughout our extended sampling period suggesting transiency with high turnover. Together, this study documents demographic separation during the non-breeding period with preference for of secondary forest and high transiency, important findings in informing management across the annual cycle.
25.	Jefferson, Amanda, et al. (författare) Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence 2016 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2 Tidskriftsartikel (refereegranskat)abstract ObjectivesWe developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians.MethodsAn initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions.ResultsAgreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended.ConclusionA clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.
26.	Kiemeney, Lambertus A, et al. (författare) A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. 2010 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9 Tidskriftsartikel (refereegranskat)abstract Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
27.	Larkin, Cormac J.K., et al. (författare) M5 — Mars Magnetospheric Multipoint Measurement Mission: A multi-spacecraft plasma physics mission to Mars 2024 Ingår i: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 73:6, s. 3235-3255 Tidskriftsartikel (refereegranskat)abstract Mars, lacking an intrinsic dynamo, is an ideal laboratory to comparatively study induced magnetospheres, which can be found in other terrestrial bodies as well as comets. Additionally, Mars is of particular interest to further exploration due to its loss of habitability by atmospheric escape and possible future human exploration. In this context, we propose the Mars Magnetospheric Multipoint Measurement Mission (M5), a multi-spacecraft mission to study the dynamics and energy transport of the Martian induced magnetosphere comprehensively. Particular focus is dedicated to the largely unexplored magnetotail region, where signatures of magnetic reconnection have been found. Furthermore, a reliable knowledge of the upstream solar wind conditions is needed to study the dynamics of the Martian magnetosphere, especially the different dayside boundary regions but also for energy transport phenomena like the current system and plasma waves. This will aid the study of atmospheric escape processes of planets with induced magnetospheres. In order to resolve the three-dimensional structures varying both in time and space, multi-point measurements are required. Thus, M5 is a five spacecraft mission, with one solar wind monitor orbiting Mars in a circular orbit at 5 Martian radii, and four smaller spacecraft in a tetrahedral configuration orbiting Mars in an elliptical orbit, spanning the far magnetotail up to 6 Mars radii with a periapsis just outside the Martian magnetosphere of 1.8 Mars radii. We not only present a detailed assessment of the scientific need for such a mission but also show the resulting mission and spacecraft design taking into account all aspects of the mission requirements and constraints such as mass, power, and link budgets. Additionally, different aspects of the mission programmatics like a possible mission timeline, cost estimates, or public outreach are shown. The common requirements for acceptance for an ESA mission are considered. The mission outlined in this paper was developed during the Alpbach Summer School 2022 on the topic of “Comparative Plasma Physics in the Universe”.
28.	Le Contel, O., et al. (författare) Lower Hybrid Drift Waves and Electromagnetic Electron Space-Phase Holes Associated With Dipolarization Fronts and Field-Aligned Currents Observed by the Magnetospheric Multiscale Mission During a Substorm 2017 Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:12, s. 12236-12257 Tidskriftsartikel (refereegranskat)abstract We analyze two ion scale dipolarization fronts associated with field-aligned currents detected by the Magnetospheric Multiscale mission during a large substorm on 10 August 2016. The first event corresponds to a fast dawnward flow with an antiparallel current and could be generated by the wake of a previous fast earthward flow. It is associated with intense lower hybrid drift waves detected at the front and propagating dawnward with a perpendicular phase speed close to the electric drift and the ion thermal velocity. The second event corresponds to a flow reversal: from southwward/dawnward to northward/duskward associated with a parallel current consistent with a brief expansion of the plasma sheet before the front crossing and with a smaller lower hybrid drift wave activity. Electromagnetic electron phase-space holes are detected near these low-frequency drift waves during both events. The drift waves could accelerate electrons parallel to the magnetic field and produce the parallel electron drift needed to generate the electron holes. Yet we cannot rule out the possibility that the drift waves are produced by the antiparallel current associated with the fast flows, leaving the source for the electron holes unexplained.
29.	Luck, Gary W., et al. (författare) Quantifying the Contribution of Organisms to the Provision of Ecosystem Services 2009 Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 59:3, s. 223-235 Tidskriftsartikel (refereegranskat)abstract Research on ecosystem services has grown rapidly over the last decade. Two conceptual frameworks have been published to guide ecological assessments of organisms that deliver services-the concepts of service-providing units (SPUs) and ecosystem service providers (ESPs). Here, we unite these frameworks and present an SPU-ESP continuum that offers a coherent conceptual approach for synthesizing the latest developments in ecosystem service research, and can direct future studies at all levels of organization. In particular, we show how the service-provider concept call be applied tit the population, functional group, and community levels, We strongly emphasize the need to identify and quantify the organisms and their characteristics (e.g., functional traits) that provide services, and to assess service provision relative to the demands of human beneficiaries. We use key examples from the literature to illustrate the new approach and to highlight gaps in knowledge, particularly in relation to the impact of species interactions and ecosystem dynamics on service provision.
30.	Ludvigsson, Jonas F., 1969-, et al. (författare) Diagnosis and management of adult coeliac disease : guidelines from the British Society of Gastroenterology 2014 Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 63:8, s. 1210-1228 Tidskriftsartikel (refereegranskat)abstract A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
31.	Ludvigsson, Jonas F., et al. (författare) The Oslo definitions for coeliac disease and related terms 2013 Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 62:1, s. 43-52 Tidskriftsartikel (refereegranskat)abstract Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
32.	Lundtoft, Christian, et al. (författare) Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases 2022 Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:8, s. 1440-1450 Tidskriftsartikel (refereegranskat)abstract Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.
33.	Mendelson, Michael M., et al. (författare) Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease : A Mendelian Randomization Approach 2017 Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.
34.	Moss, Brian D., et al. (författare) Climate change and the future of freshwater biodiversity in Europe : a primer for policy-makers 2009 Ingår i: Freshwater Reviews. - : Freshwater Biological Association. - 1755-084X. ; 2:2, s. 103-130 Tidskriftsartikel (refereegranskat)abstract Earth's climate is changing, and by the end of the 21st century in Europe, average temperatures are likely to have risen by at least 2 °C, and more likely 4 °C with associated effects on patterns of precipitation and the frequency of extreme weather events. Attention among policy-makers is divided about how to minimise the change, how to mitigate its effects, how to maintain the natural resources on which societies depend and how to adapt human societies to the changes. Natural systems are still seen, through a long tradition of conservation management that is largely species-based, as amenable to adaptive management, and biodiversity, mostly perceived as the richness of plant and vertebrate communities, often forms a focus for planning. We argue that prediction of particular species changes will be possible only in a minority of cases but that prediction of trends in general structure and operation of four generic freshwater ecosystems (erosive rivers, depositional floodplain rivers, shallow lakes and deep lakes) in three broad zones of Europe (Mediterranean, Central and Arctic-Boreal) is practicable. Maintenance and rehabilitation of ecological structures and operations will inevitably and incidentally embrace restoration of appropriate levels of species biodiversity. Using expert judgement, based on an extensive literature, we have outlined, primarily for lay policy makers, the pristine features of these systems, their states under current human impacts, how these states are likely to alter with a warming of 2 °C to 4 °C and what might be done to mitigate this. We have avoided technical terms in the interests of communication, and although we have included full referencing as in academic papers, we have eliminated degrees of detail that could confuse broad policy-making
35.	Multimessenger observations of a flaring blazar coincident with high-energy neutrino IceCube-170922A 2018 Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 361:6398 Tidskriftsartikel (refereegranskat)
36.	Nicolas, Aude, et al. (författare) Genome-wide Analyses Identify KIF5A as a Novel ALS Gene 2018 Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6 Tidskriftsartikel (refereegranskat)abstract To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
37.	Oji, Vinzenz, et al. (författare) Revised nomenclature and classification of inherited ichthyoses : Results of the First Ichthyosis Consensus Conference in Sorèze 2009 2010 Ingår i: The Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 63:4, s. 607-641 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. OBJECTIVE: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. METHODS: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Sorèze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. RESULTS: It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"-under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. LIMITATIONS: As more becomes known about these diseases in the future, modifications will be needed. CONCLUSION: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.
38.	Popp, David, et al. (författare) Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser 2017 Ingår i: CYTOSKELETON. - : WILEY. - 1949-3584 .- 1949-3592. ; 74:12, s. 472-481 Tidskriftsartikel (refereegranskat)abstract A major goal for X-ray free-electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single macromolecular structures elucidated by XFEL radiation, since they contain one-dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments (Escherichia coli pili, F-actin, and amyloid fibrils), which when intersected by femtosecond X-ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determine that F-actin can be flow-aligned to a disorientation of approximately 5 degrees. Using this XFEL-based technique, we determine that gelsolin amyloids are comprised of stacked -strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual -synuclein amyloids.
39.	Potapov, Anton M., et al. (författare) Global fine-resolution data on springtail abundance and community structure 2024 Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
40.	Potapov, Anton M., et al. (författare) Globally invariant metabolism but density-diversity mismatch in springtails 2023 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.
41.	Powers, Mark B., et al. (författare) Nonpharmacologic Pain Management Among Hospitalized Inpatients : A Randomized Waitlist-Controlled Trial of Standard Virtual Reality (CGI VR) Versus Video Capture VR (360 degrees 3D/Stereoscopic Video Capture VR) 2021 Ingår i: The Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 37:9, s. 678-687 Tidskriftsartikel (refereegranskat)abstract Objectives: Nonpharmacologic pain management strategies are needed because of the growing opioid epidemic. While studies have examined the efficacy of virtual reality (VR) for pain reduction, there is little research in adult inpatient settings, and no studies comparing the relative efficacy of standard animated computer-generated imagery (CGI) VR to Video Capture VR (360 degrees 3D/stereoscopic Video Capture VR). Here, we report on a randomized controlled trial of the relative efficacy of standard CGI VR versus Video Capture VR (matched for content) and also compared the overall efficacy of VR to a waitlist control group.Materials and Methods: Participants (N=103 hospitalized inpatients reporting pain) were randomized to 1 of 3 conditions: (1) waitlist control, (2) CGI VR, or (3) Video Capture VR. The VR and waitlist conditions were 10 minutes in length. Outcomes were assessed pretreatment, post-treatment, and after a brief follow-up.Results: Consistent with hypotheses, both VR conditions reduced pain significantly more relative to the waitlist control condition (d=1.60, P<0.001) and pain reductions were largely maintained at the brief follow-up assessment. Both VR conditions reduced pain by ∼50% and led to improvements in mood, anxiety, and relaxation. Contrary to prediction, the Video Capture VR condition was not significantly more effective at reducing pain relative to the CGI VR condition (d=0.25, P=0.216). However, as expected, patients randomized to the Video Capture VR rated their experience as more positive and realistic (d=0.78, P=0.002).Discussion: Video Capture VR was as effective as CGI VR for pain reduction and was rated as more realistic.
42.	Ravn, Christen, et al. (författare) Guideline for management of septic arthritis in native joints (SANJO) 2023 Ingår i: Journal of bone and joint infection. - : Copernicus. - 2206-3552. ; 8:1, s. 29-37 Tidskriftsartikel (refereegranskat)abstract This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.
43.	Robinson, Matthew R., et al. (författare) Population genetic differentiation of height and body mass index across Europe 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:11, s. 1357-1362 Tidskriftsartikel (refereegranskat)abstract Across-nation differences in the mean values for complex traits are common(1-8), but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 x 10(-8); BMI, P < 5.95 x 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
44.	Rubin, Adam, et al. (författare) TYPE II SUPERNOVA ENERGETICS AND COMPARISON OF LIGHT CURVES TO SHOCK-COOLING MODELS 2016 Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 820:1 Tidskriftsartikel (refereegranskat)abstract During the first few days after explosion, Type II supernovae (SNe) are dominated by relatively simple physics. Theoretical predictions regarding early-time SN light curves in the ultraviolet (UV) and optical bands are thus quite robust. We present, for the first time, a sample of 57 R-band SN II light curves that are well-monitored during their rise, with > 5 detections during the first 10 days after discovery, and a well-constrained time of explosion to within 1-3 days. We show that the energy per unit mass (E/M) can be deduced to roughly a factor of five by comparing early-time optical data to the 2011 model of Rabinak & Waxman, while the progenitor radius cannot be determined based on R-band data alone. We find that SN II explosion energies span a range of E/M = (0.2-20) x 10(51) erg/(10 M-circle dot), and have a mean energy per unit mass of < E/M > = 0.85 x 10(51) erg/(10 M-circle dot), corrected for Malmquist bias. Assuming a small spread in progenitor masses, this indicates a large intrinsic diversity in explosion energy. Moreover, E/M is positively correlated with the amount of Ni-56 produced in the explosion, as predicted by some recent models of core-collapse SNe. We further present several empirical correlations. The peak magnitude is correlated with the decline rate (Delta m(15)), the decline rate is weakly correlated with the rise time, and the rise time is not significantly correlated with the peak magnitude. Faster declining SNe are more luminous and have longer rise times. This limits the possible power sources for such events.
45.	Speakman, John R., et al. (författare) Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure 2023 Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
46.	Sproviero, William, et al. (författare) ATXN2 trinucleotide repeat length correlates with risk of ALS 2017 Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 178.e1-178.e9 Tidskriftsartikel (refereegranskat)abstract We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.
47.	Telloni, Daniele, et al. (författare) Exploring the Solar Wind from Its Source on the Corona into the Inner Heliosphere during the First Solar Orbiter-Parker Solar Probe Quadrature 2021 Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 920:1 Tidskriftsartikel (refereegranskat)abstract This Letter addresses the first Solar Orbiter (SO)-Parker Solar Probe (PSP) quadrature, occurring on 2021 January 18 to investigate the evolution of solar wind from the extended corona to the inner heliosphere. Assuming ballistic propagation, the same plasma volume observed remotely in the corona at altitudes between 3.5 and 6.3 solar radii above the solar limb with the Metis coronagraph on SO can be tracked to PSP, orbiting at 0.1 au, thus allowing the local properties of the solar wind to be linked to the coronal source region from where it originated. Thanks to the close approach of PSP to the Sun and the simultaneous Metis observation of the solar corona, the flow-aligned magnetic field and the bulk kinetic energy flux density can be empirically inferred along the coronal current sheet with an unprecedented accuracy, allowing in particular estimation of the Alfven radius at 8.7 solar radii during the time of this event. This is thus the very first study of the same solar wind plasma as it expands from the sub-Alfvenic solar corona to just above the Alfven surface.
48.	Telloni, Daniele, et al. (författare) Linking Small-scale Solar Wind Properties with Large-scale Coronal Source Regions through Joint Parker Solar Probe-Metis/Solar Orbiter Observations 2022 Ingår i: Astrophysical Journal. - : IOP Publishing Ltd. - 0004-637X .- 1538-4357. ; 935:2 Tidskriftsartikel (refereegranskat)abstract The solar wind measured in situ by Parker Solar Probe in the very inner heliosphere is studied in combination with the remote-sensing observation of the coronal source region provided by the METIS coronagraph aboard Solar Orbiter. The coronal outflows observed near the ecliptic by Metis on 2021 January 17 at 16:30 UT, between 3.5 and 6.3 R (circle dot) above the eastern solar limb, can be associated with the streams sampled by PSP at 0.11 and 0.26 au from the Sun, in two time intervals almost 5 days apart. The two plasma flows come from two distinct source regions, characterized by different magnetic field polarity and intensity at the coronal base. It follows that both the global and local properties of the two streams are different. Specifically, the solar wind emanating from the stronger magnetic field region has a lower bulk flux density, as expected, and is in a state of well-developed Alfvenic turbulence, with low intermittency. This is interpreted in terms of slab turbulence in the context of nearly incompressible magnetohydrodynamics. Conversely, the highly intermittent and poorly developed turbulent behavior of the solar wind from the weaker magnetic field region is presumably due to large magnetic deflections most likely attributed to the presence of switchbacks of interchange reconnection origin.
49.	van Doormaal, Perry T. C., et al. (författare) The role of de novo mutations in the development of amyotrophic lateral sclerosis 2017 Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 38:11, s. 1534-1541 Tidskriftsartikel (refereegranskat)abstract The genetic basis combined with the sporadic occurrence of amyotrophic lateral sclerosis (ALS) suggests a role of de novo mutations in disease pathogenesis. Previous studies provided some evidence for this hypothesis; however, results were conflicting: no genes with recurrent occurring de novo mutations were identified and different pathways were postulated. In this study, we analyzed whole-exome data from 82 new patient-parents trios and combined it with the datasets of all previously published ALS trios (173 trios in total). The per patient de novo rate was not higher than expected based on the general population (P = 0.40). We showed that these mutations are not part of the previously postulated pathways, and gene-gene interaction analysis found no enrichment of interacting genes in this group (P = 0.57). Also, we were able to show that the de novo mutations in ALS patients are located in genes already prone for de novo mutations (P < 1 x 10(-15)). Although the individual effect of rare de novo mutations in specific genes could not be assessed, our results indicate that, in contrast to previous hypothesis, de novo mutations in general do not impose a major burden on ALS risk.
50.	Veiseh, Mandana, et al. (författare) Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes 2012 Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 13:1, s. 12-22 Tidskriftsartikel (refereegranskat)abstract An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, Tc-99m-HA, and iodine-HA, I-125-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (Tc-99m-HA), breast cancer. cells/xenografts (TR-HA, Gd-HA), and vascular injury (I-125-HA, TR-HA). Targeting of HA probes to these sites. appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require, polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues.

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