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- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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3. |
- Feng, Shaohong, et al.
(author)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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4. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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7. |
- Aronsson, Helena, et al.
(author)
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Mellangrödor i växtföljden - för kolinlagring och effektivt kväveutnyttjande
- 2023
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Reports (other academic/artistic)abstract
- Rapporten beskriver mellangrödors funktion för kolinlagring i jordbruksmark i relation till andra funktioner och miljörisker. Den består av en kunskapsgenomgång, en inventering av data från fältförsök samt en sammanfattning av odlares erfarenheter vid en workshop. Vår definition av mellangröda är: En gröda som har sin huvudsakliga tillväxt mellan två huvudgrödor, och där syftet med att odla mellangrödan kan variera.Mellangrödan ger kolinlagring, särskilt rötternaKolinlagringen av en mellangröda har uppskattats till ca 320 kg kol i medeltal per ha och år, men variationen är stor. Vi sammanställde resultat från fältförsök med mellangrödor under 30 år. För insådda gräsfånggrödor skiljer sig biomassaproduktionen i medeltal inte så mycket åt mellan olika regioner, medan variationen är större för eftersådda mellangrödor. Det saknas kunskap för att kunna ge konkreta råd om hur artval och jordbearbetningsstrategier m.m. för mellangröda kan användas för att optimera stabiliseringsprocesserna för kol i marken. Mellangrödans rötter bidrar med ca 2,5 gånger större inlagring än den ovanjordiska grönmassan. Mätningar vi funnit visar en stor variation i viktförhållandet mellan skott och rot, som beror på arters variation, men också på osäkerheter i provtagning och metoder.Utmaningar för odlarnaBåde försök och odlares erfarenheter vittnar om utmaningar med sådd av mellangrödor efter skörd, särskilt på jordar med hög lerhalt. Det handlar om att hinna så direkt efter huvudgrödans skörd för att lyckas med etableringen och för att utnyttja hösten för tillväxt. Att ge sådd av mellangrödan lika hög prioritet som en huvudgröda var ett råd som erfarna odlare poängterade vid en workshop. Det finns olika tankesätt och strategier kring val av arter, beroende på syftet med mellangrödan. Genom artblandningar kan man också kombinera funktioner. Det finns inga tydliga råd för arter som särskilt främjar kolinlagring utan det viktigaste är stor tillväxt, hög kol-kväve-kvot (C/N-kvot), stor rotbiomassa samt baljväxtinslag. Hushållning med kvävet En nordisk sammanställning visade att mellangrödor i medeltal minskade kväveläckaget med drygt 40 %. Tidpunkt för nedbrukning eller kemisk avdödning är metoder för att styra återmineraliseringen och kväveverkan i nästa gröda. För frostkänsliga mellangrödor med låg C/N-kvot finns en risk att kvävet frigörs så snabbt att det hinner utlakas innan våren. Under sådana förhållanden ökar också risken för lustgasemissioner. Mer kunskap behövs om hur kväveomsättning påverkas och hur lustgasemissioner kan minimeras, för att kunna anpassa mellangrödesystemen efter olika odlingskrav och klimatets förändring.
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8. |
- Bäckström, Malin, 1967, et al.
(author)
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Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells.
- 2003
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In: The Biochemical journal. - 1470-8728. ; 376:Pt 3, s. 677-86
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Journal article (peer-reviewed)abstract
- We have developed an expression system for the production of large quantities of recombinant MUC1 mucin in CHO-K1 (Chinese-hamster ovary K1) cells. The extracellular part of human MUC1, including 16 MUC1 tandem repeats, was produced as a fusion protein with murine IgG Fc, with an intervening enterokinase cleavage site for the removal of the Fc tail. Stable MUC1-IgG-producing CHO-K1 clones were generated and were found to secrete MUC1-IgG into the culture medium. After adaptation to suspension culture in protein-free medium in a bioreactor, the fusion protein was secreted in large quantities (100 mg/l per day) into the culture supernatant. From there, MUC1 could be purified to homogeneity using a two-step procedure including enterokinase cleavage and ion-exchange chromatography. Capillary liquid chromatography MS of released oligosaccharides from CHO-K1-produced MUC1 identified the main O-glycans as Galbeta1-3GalNAc (core 1) and mono- and di-sialylated core 1. The glycans occupied on average 4.3 of the five potential O-glycosylation sites in the tandem repeats, as determined by nano-liquid chromatography MS of partially deglycosylated Clostripain-digested protein. A very similar O-glycan profile and site occupancy was found in MUC1-IgG produced in the breast carcinoma cell line T47D, which has O-glycosylation typical for breast cancer. In contrast, MUC1-IgG produced in another breast cancer cell line, MCF-7, showed a more complex pattern with both core 1- and core 2-based O-glycans. This is the first reported production of large quantities of recombinant MUC1 with a breast cancer-like O-glycosylation that could be used for the immunotherapy of breast cancer.
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9. |
- Carlstedt, Thomas, et al.
(author)
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Cortical activity and hand function restoration in a patient after spinal cord surgery
- 2009
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In: NATURE REVIEWS NEUROLOGY. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 5:10, s. 571-574
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Journal article (peer-reviewed)abstract
- Background. Following a motorcycle accident, a 9-year-old boy experienced a complete right-sided ( dominant) arm and hand paralysis with total sensory loss, Horner syndrome and severe constant pain. This study assessed the long-term outcome of spinal cord surgery undertaken on the patient, focusing on the restored hand function and related cortical activity. The study follows on from previous reports on the same patient. Investigations. Clinical functional and electrophysiological examinations. Functional MRI of cortical activity. Diagnosis. Complete brachial plexus (C5-T1) avulsion from the spinal cord. Management. Spinal cord surgery to restore motor trajectories.
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10. |
- Claussnitzer, Melina, et al.
(author)
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Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.
- 2014
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 156:1-2, s. 343-358
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.
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