| 1. |
- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 2. |
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| 3. |
- Eriksson, Anders I., et al.
(författare)
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Cold and warm electrons at comet 67P/Churyumov-Gerasimenko
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Context. Strong electron cooling on the neutral gas in cometary comae has been predicted for a long time, but actual measurements of low electron temperature are scarce. Aims. Our aim is to demonstrate the existence of cold electrons in the inner coma of comet 67P/Churyumov-Gerasimenko and show filamentation of this plasma. Methods. In situ measurements of plasma density, electron temperature and spacecraft potential were carried out by the Rosetta Langmuir probe instrument, LAP. We also performed analytical modelling of the expanding two-temperature electron gas. Results. LAP data acquired within a few hundred km from the nucleus are dominated by a warm component with electron temperature typically 5-10 eV at all heliocentric distances covered (1.25 to 3.83 AU). A cold component, with temperature no higher than about 0.1 eV, appears in the data as short (few to few tens of seconds) pulses of high probe current, indicating local enhancement of plasma density as well as a decrease in electron temperature. These pulses first appeared around 3 AU and were seen for longer periods close to perihelion. The general pattern of pulse appearance follows that of neutral gas and plasma density. We have not identified any periods with only cold electrons present. The electron flux to Rosetta was always dominated by higher energies, driving the spacecraft potential to order -10 V. Conclusions. The warm (5-10 eV) electron population observed throughout the mission is interpreted as electrons retaining the energy they obtained when released in the ionisation process. The sometimes observed cold populations with electron temperatures below 0.1 eV verify collisional cooling in the coma. The cold electrons were only observed together with the warm population. The general appearance of the cold population appears to be consistent with a Haser-like model, implicitly supporting also the coupling of ions to the neutral gas. The expanding cold plasma is unstable, forming filaments that we observe as pulses.
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| 4. |
- Johansson, Fredrik L., et al.
(författare)
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Rosetta photoelectron emission and solar ultraviolet flux at comet 67P
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469, s. S626-S635
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Tidskriftsartikel (refereegranskat)abstract
- The Langmuir Probe instrument on Rosetta monitored the photoelectron emission current of the probes during the Rosetta mission at comet 67P/Churyumov-Gerasimenko, in essence acting as a photodiode monitoring the solar ultraviolet radiation at wavelengths below 250 nm. We have used three methods of extracting the photoelectron saturation current from the Langmuir probe measurements. The resulting data set can be used as an index of the solar far and extreme ultraviolet at the Rosetta spacecraft position, including flares, in wavelengths which are important for photoionization of the cometary neutral gas. Comparing the photoemission current to data measurements by MAVEN/EUVM and TIMED/SEE, we find good correlation when 67P was at large heliocentric distances early and late in the mission, but up to 50 per cent decrease of the expected photoelectron current at perihelion. We discuss possible reasons for the photoemission decrease, including scattering and absorption by nanograins created by disintegration of cometary dust far away from the nucleus.
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| 5. |
- Kitaguchi, Y., et al.
(författare)
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Controlling single-molecule junction conductance by molecular interactions
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak pi-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment.
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| 6. |
- Okuyama, H, et al.
(författare)
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Modifying current-voltage characteristics of a single molecule junction by isotope substitution : OHOD dimer on Cu(110)
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 85:20
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Tidskriftsartikel (refereegranskat)abstract
- Vibrationally induced configurational change and nonlinear current-voltage (I-V) characteristics are investigated within the scanning tunneling microscope (STM) junction, including hydroxyl dimers on a Cu(110) surface. H-bonded hydroxyl dimers composed of OH and/or OD have a unique inclined geometry that can be switched back and forth by vibrational excitations via the inelastic electron tunneling process of the STM. The relative occupation change between the high-and low-conductance states as a function of bias voltage critically depends on the isotopic compositions, and thus the I-V characteristics can be modified to exhibit negative differential resistance by H/D substitution. The experimental results of the occupation change and I-V curves are nicely reproduced using a recently proposed analytical model combined with comprehensive density functional calculations for the input parameters (vibrational modes and their emission rates by tunneling electrons, conductance, and relative occupation change of high-and low-conductance states), and they underlines the different roles played by the free and shared O-H(D) stretch modes of the hydroxyl dimers on a Cu(110) surface.
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| 7. |
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| 8. |
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| 9. |
- Wayne, Greg, et al.
(författare)
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Principles of Systems Biology, No. 11
- 2016
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Ingår i: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 3:5, s. 406-410
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Tidskriftsartikel (refereegranskat)abstract
- This month: AI that learns patterns and facts, new protein-RNA and protein-protein relationships, engineering signaling and metabolism, and more variants of Cas9.
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| 10. |
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| 11. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 12. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 13. |
- Andersson, A., et al.
(författare)
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FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- During 1995-2004, 209 children/adolescents were diagnosed with acute lymphoblastic or myeloid leukemia (ALL, AML) in Southern Sweden, of which 177 (85%), comprising 128 B-lineage ALL, 34 AML, and 15 T-cell ALL, could be analyzed for internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD, mutually exclusive) were detected. None of the T-cell ALL harbored any mutations. ITD and ATKD were found in 2% and 6% of the B-lineage ALL and in 12% and 9% of the AML, being particularly common in high hyperdiploid ALL (14%), ALL (20%), and AML (23%) with 11q23/MLL rearrangements, and in AML with a normal karyotype (60%). All ATKD-positive AML with MLL rearrangements harbored the t(9,11)(p21,q23). Global gene expression data were available for 76 of the B-lineage ALL and 19 of the AML, of which 6 (8%) and 3 (16%) had FLT3 mutations, respectively. No distinct expression pattern associated with FLT3 mutations was identified. © 2007 Wiley-Liss, Inc.
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| 14. |
- Aumailley, M, et al.
(författare)
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A simplified laminin nomenclature
- 2005
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Ingår i: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 24:5, s. 326-332
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Forskningsöversikt (refereegranskat)abstract
- A simplification of the laminin nomenclature is presented. Laminins are multidomain heterotrimers composed of alpha, beta and gamma chains. Previously, laminin trimers were numbered with Arabic numerals in the order discovered, that is laminins-1 to -5. We introduce a new identification system for a trimer using three Arabic numerals, based on the alpha, beta and gamma chain numbers. For example, the laminin with the chain composition alpha 5 beta 1 gamma 1 is termed laminin-511, and not laminin-10. The current practice is also to mix two overlapping domain and module nomenclatures. Instead of the older Roman numeral nomenclature and mixed nomenclature, all modules are now called domains. Some domains are renamed or renumbered. Laminin epidermal growth factor-like (LE) domains are renumbered starting at the N-termini, to be consistent with general protein nomenclature. Domain IVb of alpha chains is named laminin 4a (L4a), domain IVa of alpha chains is named L4b, domain IV of gamma chains is named L4, and domain IV of beta chains is named laminin four (LF). The two coiled-coil domains I and II are now considered one laminin coiled-coil domain (LCC). The interruption in the coiled-coil of 13 chains is named laminin beta-knob (L beta) domain. The chain origin of a domain is specified by the chain nomenclature, such as alpha IL4a. The abbreviation LM is suggested for laminin. Otherwise, the nomenclature remains unaltered.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Cederstrom, S., et al.
(författare)
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New candidate genes for ST-elevation myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:1, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite extensive research in atherosclerosis, the mechanisms of coronary atherothrombosis in ST-elevation myocardial infarction (STEMI) patients are undetermined. Objectives Our aim was to find candidate genes involved in STEMI by analysing leucocyte gene expression in STEMI patients, without the influence of secondary inflammation from innate immunity, which was assumed to be a consequence rather than the cause of coronary atherothrombosis. Methods Fifty-one patients were included at coronary angiography because of STEMI. Arterial blood was sampled in the acute phase (P1), at 24-48 h (P2) and at 3 months (P3). Leucocyte RNA was isolated and gene expression analysis was performed by Affymetrix Human Transcriptome Array 2.0. By omission of up- or downregulated genes at P2, secondary changes from innate immunity were excluded. Genes differentially expressed in P1 when compared to the convalescent sample in P3 were determined as genes involved in STEMI. Results Three genes were upregulated at P1 compared to P3; ABCG1 (P = 5.81 x 10(-5)), RAB20 (P = 3.69 x 10(-5)) and TMEM2 (P = 7.75 x 10(-6)) whilst four were downregulated; ACVR1 (P = 9.01 x 10(-5)), NFATC2IP (P = 8.86 x 10(-5)), SUN1 (P = 3.87 x 10(-5)) and TTC9C (P = 7.18 x 10(-6)). These genes were also highly expressed in carotid atherosclerotic plaques. Conclusions We found seven genes involved in STEMI. The study is unique regarding the blood sampling in the acute phase and omission of secondary expressed genes from innate immunity. However, the results need to be replicated by future studies.
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| 20. |
- Davidsson, Josef, et al.
(författare)
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Relapsed childhood high hyperdiploid acute lymphoblastic leukemia : presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations.
- 2010
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 24:5, s. 924-31
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Tidskriftsartikel (refereegranskat)abstract
- Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P<0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution with some changes conserved, lost or gained (7 of 11), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern.
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| 21. |
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| 22. |
- Elezagic, D., et al.
(författare)
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Antimicrobial peptides derived from the cartilage.-specific C-type Lectin Domain Family 3 Member A (CLEC3A) – potential in the prevention and treatment of septic arthritis
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the antimicrobial activity of peptides derived from C-type Lectin Domain Family 3 Member A (CLEC3A), shed light on the mechanism of antimicrobial activity and assess their potential application in prevention and treatment of septic arthritis. Design: We performed immunoblot to detect CLEC3A peptides in human cartilage extracts. To investigate their antimicrobial activity, we designed peptides and recombinantly expressed CLEC3A domains and used them to perform viable count assays using E.coli, P.aeruginosa and S.aureus. We investigated the mechanism of their antimicrobial activity by fluorescence and scanning electron microscopy, performed ELISA-style immunoassays and transmission electron microscopy to test for lipopolysaccharide binding and surface plasmon resonance to test for lipoteichoic acid (LTA) binding. We coated CLEC3A peptides on titanium, a commonly used prosthetic material, and performed fluorescence microscopy to quantify bacterial adhesion. Moreover, we assessed the peptides’ cytotoxicity against primary human chondrocytes using MTT cell viability assays. Results: CLEC3A fragments were detected in human cartilage extracts. Moreover, bacterial supernatants lead to fragmentation of recombinant and cartilage-derived CLEC3A. CLEC3A-derived peptides killed E.coli, P.aeruginosa and S.aureus, permeabilized bacterial membranes and bound lipopolysaccharide and LTA. Coating CLEC3A antimicrobial peptides (AMPs) on titanium lead to significantly reduced bacterial adhesion to the material. In addition, microbicidal concentrations of CLEC3A peptides in vitro displayed no direct cytotoxicity against primary human chondrocytes. Conclusions: We identify cartilage-specific AMPs originating from CLEC3A, resolve the mechanism of their antimicrobial activity and point to a novel approach in the prevention and treatment of septic arthritis using potent, non-toxic, AMPs.
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| 23. |
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| 24. |
- Frederiksen, T., et al.
(författare)
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Theory of action spectroscopy for single-molecule reactions induced by vibrational excitations with STM
- 2014
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 89:3, s. 035427-
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Tidskriftsartikel (refereegranskat)abstract
- A theory of action spectroscopy, i.e., a reaction rate or yield as a function of bias voltage, is presented for single-molecule reactions induced by the inelastic tunneling current with a scanning tunneling microscope. A formula for the reaction yield is derived using the adsorbate resonance model, which provides a versatile tool to analyze vibrationally mediated reactions of single adsorbates on conductive surfaces. This allows us to determine the energy quantum of the excited vibrational mode, the effective broadening of the vibrational density of states (as described by Gaussian or Lorentzian functions), and a prefactor characterizing the elementary process behind the reaction. The underlying approximations are critically discussed. We point out that observation of reaction yields at both bias voltage polarities can provide additional insight into the adsorbate density of states near the Fermi level. As an example, we apply the theory to the case of flip motion of a hydroxyl dimer (OD)(2) on Cu(110) which was experimentally observed by Kumagai et al. [Phys. Rev. B 79, 035423 (2009)]. In combination with density functional theory calculations for the vibrational modes, the vibrational damping due to electron-hole pair generation, and the potential energy landscape for the flip motion, a detailed microscopic picture for the switching process is established. This picture reveals that the predominant mechanism is excitation of the OD stretch modes which couple anharmonically to the low-energy frustrated rotation mode.
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| 25. |
- Gallina, AL, et al.
(författare)
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AMPA-Type Glutamate Receptors Associated With Vascular Smooth Muscle Cell Subpopulations in Atherosclerosis and Vascular Injury
- 2021
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Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 8, s. 655869-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives and Aims: Vascular smooth muscle cells (VSMCs) are key constituents of both normal arteries and atherosclerotic plaques. They have an ability to adapt to changes in the local environment by undergoing phenotypic modulation. An improved understanding of the mechanisms that regulate VSMC phenotypic changes may provide insights that suggest new therapeutic targets in treatment of cardiovascular disease (CVD). The amino-acid glutamate has been associated with CVD risk and VSMCs metabolism in experimental models, and glutamate receptors regulate VSMC biology and promote pulmonary vascular remodeling. However, glutamate-signaling in human atherosclerosis has not been explored.Methods and Results: We identified glutamate receptors and glutamate metabolism-related enzymes in VSMCs from human atherosclerotic lesions, as determined by single cell RNA sequencing and microarray analysis. Expression of the receptor subunits glutamate receptor, ionotropic, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA)-type subunit 1 (GRIA1) and 2 (GRIA2) was restricted to cells of mesenchymal origin, primarily VSMCs, as confirmed by immunostaining. In a rat model of arterial injury and repair, changes of GRIA1 and GRIA2 mRNA level were most pronounced at time points associated with VSMC proliferation, migration, and phenotypic modulation. In vitro, human carotid artery SMCs expressed GRIA1, and selective AMPA-type receptor blocking inhibited expression of typical contractile markers and promoted pathways associated with VSMC phenotypic modulation. In our biobank of human carotid endarterectomies, low expression of AMPA-type receptor subunits was associated with higher content of inflammatory cells and a higher frequency of adverse clinical events such as stroke.Conclusion: AMPA-type glutamate receptors are expressed in VSMCs and are associated with phenotypic modulation. Patients suffering from adverse clinical events showed significantly lower mRNA level of GRIA1 and GRIA2 in their atherosclerotic lesions compared to asymptomatic patients. These results warrant further mapping of neurotransmitter signaling in the pathogenesis of human atherosclerosis.
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| 26. |
- Glantz, Maria, et al.
(författare)
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Importance of casein micelle size and milk composition for milk gelation.
- 2010
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 93:4, s. 1444-1451
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Tidskriftsartikel (refereegranskat)abstract
- The economic output of the dairy industry is to a great extent dependent on the processing of milk into other milk-based products such as cheese. The yield and quality of cheese are dependent on both the composition and technological properties of milk. The objective of this study was to evaluate the importance and effects of casein (CN) micelle size and milk composition on milk gelation characteristics in order to evaluate the possibilities for enhancing gelation properties through breeding. Milk was collected on 4 sampling occasions at the farm level in winter and summer from dairy cows with high genetic merit, classified as elite dairy cows, of the Swedish Red and Swedish Holstein breeds. Comparisons were made with milk from a Swedish Red herd, a Swedish Holstein herd, and a Swedish dairy processor. Properties of CN micelles, such as their native and rennet-induced CN micelle size and their zeta-potential, were analyzed by photon correlation spectroscopy, and rennet-induced gelation characteristics, including gel strength, gelation time, and frequency sweeps, were determined. Milk parameters of the protein, lipid, and carbohydrate profiles as well as minerals were used to obtain correlations with native CN micelle size and gelation characteristics. Milk pH and protein, CN, and lactose contents were found to affect milk gelation. Smaller native CN micelles were shown to form stronger gels when poorly coagulating milk was excluded from the correlation analysis. In addition, milk pH correlated positively, whereas Mg and K correlated negatively with native CN micellar size. The milk from the elite dairy cows was shown to have good gelation characteristics. Furthermore, genetic progress in relation to CN micelle size was found for these cows as a correlated response to selection for the Swedish breeding objective if optimizing for milk gelation characteristics. The results indicate that selection for smaller native CN micelles and lower milk pH through breeding would enhance gelation properties and may thus improve the initial step in the processing of cheese.
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| 27. |
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| 28. |
- Hammar, Björn, et al.
(författare)
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A Novel Type of Autosomal Dominant Episodic Nystagmus Segregating with a Variant in the FRMD5 Gene
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Ingår i: Neuro-Ophthalmology. - 0165-8107.
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Tidskriftsartikel (refereegranskat)abstract
- To describe the phenotype of a novel form of autosomal dominant episodic nystagmus and to identify the potential genetic aetiology. We identified several individuals in a large Swedish family affected by episodic nystagmus. In total, 39 family members from five generations were invited to participate in the study, of which 17 were included (12 affected and 5 unaffected). The phenotype of the nystagmus was described based on data collected from family members through questionnaires, interviews, clinical examinations and from video recordings of ongoing episodes of nystagmus. Whole genome sequencing (WGS) and further Sanger sequencing for segregation of the identified candidate variants was performed in eight participants (six affected and two unaffected). The 12 affected participants showed a phenotype with episodic nystagmus of early onset. A vertical jerk nystagmus with variable amplitude and frequency was characterized in the analysed video material. No other eye pathology or other disease that could explain the episodic nystagmus was identified among the family participants. Genetic analysis identified a missense variant (p.Ser375Phe) in the gene FRMD5, which segregated with the disease in the eight individuals analysed, from three generations. We describe a novel autosomal dominant form of early onset episodic nystagmus and suggest the FRMD5 gene as a strong candidate gene for this disorder.
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| 29. |
- Hong, J, et al.
(författare)
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Erratum
- 2016
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 108:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 30. |
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| 31. |
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| 33. |
- Kabosova, Andrea, et al.
(författare)
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Compositional differences between infant and adult human corneal basement membranes
- 2007
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 48:11, s. 4989-4999
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Adult human corneal epithelial basement membrane ( EBM) and Descemet's membrane ( DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes of these components during postnatal corneal development. METHODS. Thirty healthy adult corneas and 10 corneas from 12-day- to 3-year-old children were studied by immunofluorescence with antibodies against BM components. RESULTS. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from alpha 1-alpha 2 to alpha 3-alpha 4 chains after 3 years of life; in the adult, alpha 1-alpha 2 chains were retained only in the limbal BM. Laminin alpha 2 and beta 2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, beta 2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin gamma 3 chain. In the infant DM, type IV collagen alpha 1-alpha 6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found on both faces, but they remained only on the endothelial face of the adult DM. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult. Matrilin-4 largely disappeared after the age of 3 years. CONCLUSIONS. The distribution of laminin gamma 3 chain, nidogen-2, netrin-4, matrilin-2, and matrilin-4 is described in the cornea for the first time. The observed differences between adult and infant corneal BMs may relate to changes in their mechanical strength, corneal cell adhesion and differentiation in the process of postnatal corneal maturation.
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| 34. |
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| 39. |
- Lindblom, Anders, et al.
(författare)
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The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix
- 1999
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:10, s. 6374-6380
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Tidskriftsartikel (refereegranskat)abstract
- A large protein was purified from bovine kidney, using selective extraction with EDTA to solubilize proteins anchored by divalent cation-dependent interactions. An antiserum raised against the purified protein labeled the apical cell surface of the epithelial cells in proximal tubules and the luminal surface of small intestine. Ten peptide sequences, derived from the protein, all matched the recently published sequences for rat (Moestrup, S. K., Kozyraki, R., Kristiansen, M., Kaysen, J. H., Holm Rasmussen, H., Brault, D., Pontillon, F., Goda, F. O., Christensen, E. I., Hammond, T. G., and Verroust, P. J. (1998) J. Biol. Chem. 273, 5235-5242) and human cubilin, a receptor for intrinsic factor-vitamin B12 complexes, identifying the protein as bovine cubilin. In electron microscopy, a three-armed structure was seen, indicating an oligomerization of three identical subunits. This model was supported by the Mr values of about 1,500,000 for the intact protein and 440,000 for its subunits obtained by analytical ultracentrifugation. In a search for a potential assembly domain, we identified a region of heptad repeats in the N-terminal part of the cubilin sequence. Computer-assisted analysis supported the presence of a coiled-coil alpha-helix between amino acids 103 and 132 of the human cubilin sequence and predicted the formation of a triple coiled-coil. We therefore conclude that cubilin forms a noncovalent trimer of identical subunits connected by an N-terminal coiled-coil alpha-helix.
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- Nicolson, NG, et al.
(författare)
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Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion
- 2020
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Ingår i: Endocrine pathology. - : Springer Science and Business Media LLC. - 1559-0097 .- 1046-3976. ; 31:4, s. 367-376
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Tidskriftsartikel (refereegranskat)abstract
- While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (n = 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry. E2F1 was over-expressed in all 3 subtypes (p<0.01). SP1 was differentially expressed in eaFTC and wiFTC compared with normal (p=0.01 and 0.04, respectively). TCF7L2 was significantly upregulated in wiFTC specifically (p<0.05). While these findings were mRNA specific, immunohistochemistry of additional cancer-associated transcription factors revealed differential expression along the tumor invasive front relative to the central tumor, and histone acetylation modulators emerged as putative invasion markers. These findings may have significant implications for the interpretation of bulk gene expression analysis of thyroid tumor samples or for the development of targeted therapeutics for this rare but aggressive thyroid cancer variant.
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| 47. |
- Oskarsson, Marie E., et al.
(författare)
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In Vivo Seeding and Cross-Seeding of Localized Amyloidosis A Molecular Link between Type 2 Diabetes and Alzheimer Disease
- 2015
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 185:3, s. 834-846
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Tidskriftsartikel (refereegranskat)abstract
- Several proteins have been identified as amyloid forming in humans, and independent of protein origin, the fibrils are morphologically similar. Therefore, there is a potential for structures with amyloid seeding ability to induce both homologous and heterologous fibril growth; thus, molecular interaction can constitute a Link between different amyloid forms. Intravenous injection with preformed fibrils from islet amyloid polypeptide (IAPP), proIAPP, or amyloid-beta (A beta) into human IAPP transgenic mice triggered IAPP amyloid formation in pancreas in 5 of 7 mice in each group, demonstrating that IAPP amyloid could be enhanced through homologous and heterologous seeding with higher efficiency for the former mechanism. Proximity Ligation assay was used for colocalization studies of IAPP and A beta in islet amyloid in type 2 diabetic patients and A beta deposits in brains of patients with Alzheimer disease. All reactivity was not detected in islet amyloid although islet beta cells express A beta PP and convertases necessary for A beta production. By contrast, IAPP and proIAPP were detected in cerebral and vascular A beta deposits, and presence of proximity Ligation signal at both locations showed that the peptides were <40 nm apart. It is not clear whether IAPP present in brain originates from pancreas or is Locally produced. Heterologous seeding between IAPP and All shown here may represent a molecular Link between type 2 diabetes and Alzheimer disease.
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- Padra, Médea, 1986, et al.
(författare)
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Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid.
- 2021
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Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 65:6, s. 593-602
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.
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