| 1. |
- de Zwarte, Sonja M. C., et al.
(författare)
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Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 414-430
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Tidskriftsartikel (refereegranskat)abstract
- First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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| 2. |
- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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| 3. |
- Janerot-Sjöberg, Birgitta, 1958-, et al.
(författare)
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Influence of respiration on myocardial signal intensity
- 2001
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Ingår i: Ultrasound in Medicine and Biology. - 0301-5629 .- 1879-291X. ; 27:4, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- Echocardiographic quantification of myocardial perfusion after IV contrast is possible, based on the intensity of the received intermittent second harmonic signal. To investigate the influence of respiration on the intensity of myocardial signals, we examined nine patients with normal coronary angiograms. At baseline, end-expiratory and end-inspiratory images were obtained in broadband radiofrequency (RF) and intermittent second harmonic modes, the latter repeated during IV contrast at rest and at peak stress. In mid-septum at baseline, end-inspiratory integrated backscatter intensity was 4 dB higher (p < 0.05, both in second harmonic and fundamental domains) than end-expiratory intensity. In second harmonic imaging, contrast increased signal intensity by 4 dB (p < 0.05) in six examined segments, but the increase in the midseptal region (2 dB) was not significant. Contrast-enhanced intensity at end-inspiration was higher (3 dB, p < 0.01) than baseline intensity at end-expiration. We conclude that the increase in myocardial signal intensity during inspiration may resemble the contrast effect in intermittent second harmonic mode. The respiratory variation persists after contrast and may mask or exaggerate the effect of myocardial contrast.
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| 4. |
- Mhlekude, Baxolele, et al.
(författare)
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Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection
- 2023
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:9
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant viruses, and reduced viral RNA quantities and infectious titers in the culture supernatant. While we confirmed JQ-1-mediated downregulation of expression of angiotensin-converting enzyme 2 (ACE2) and interferon-stimulated genes (ISGs), multi-omics analysis addressing the chromatin accessibility, transcriptome and proteome uncovered induction of an antiviral nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated cytoprotective response as an additional mechanism through which JQ-1 inhibits SARS-CoV-2 replication. Pharmacological inhibition of NRF-2, and knockdown of NRF-2 and its target genes reduced JQ-1-mediated inhibition of SARS-CoV-2 replication. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variant, which exhibited resistance to JQ-1 and increased sensitivity to exogenously administered type I interferon (IFN-I), suggesting a minimised need for SARS-CoV-2 ORF6-mediated repression of IFN signalling in the presence of JQ-1. Importantly, JQ-1 exhibited a transient antiviral activity when administered prophylactically in human airway bronchial epithelial cells (hBAECs), which was gradually subverted by SARS-CoV-2, and no antiviral activity when administered therapeutically following an established infection. We propose that JQ-1 exerts pleiotropic effects that collectively induce an antiviral state in the host, which is ultimately nullified by SARS-CoV-2 infection, raising questions about the clinical suitability of the iBETs in the context of COVID-19.
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| 5. |
- Möslinger, Anja, et al.
(författare)
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Solar Wind Protons Forming Partial Ring Distributions at Comet 67P
- 2023
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 128:2
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Tidskriftsartikel (refereegranskat)abstract
- We present partial ring distributions of solar wind protons observed by the Rosetta spacecraft at comet 67P/Churyumov-Gerasimenko. The formation of ring distributions is usually associated with high activity comets, where the spatial scales are larger than multiple ion gyroradii. Our observations are made at a low-activity comet at a heliocentric distance of 2.8 AU on 19 April 2016, and the partial rings occur at a spatial scale comparable to the ion gyroradius. We use a new visualization method to simultaneously show the angular distribution of median energy and differential flux. A fitting procedure extracts the bulk speed of the solar wind protons, separated into components parallel and perpendicular to the gyration plane, as well as the gyration velocity. The results are compared with models and put into context of the global comet environment. We find that the formation mechanism of these partial rings of solar wind protons is entirely different from the well-known partial rings of cometary pickup ions at high-activity comets. A density enhancement layer of solar wind protons around the comet is a focal point for proton trajectories originating from different regions of the upstream solar wind. If the spacecraft location coincides with this density enhancement layer, the different trajectories are observed as an energy-angle dispersion and manifest as partial rings in velocity space.
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| 6. |
- Richter, Kai, et al.
(författare)
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Elucidating structure-property relationships in imidazolium-based halide ionic liquids : crystal structures and thermal behavior
- 2020
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Ingår i: Zeitschrift für Kristallographie - Crystalline Materials. - : Walter de Gruyter GmbH. - 2194-4946 .- 2196-7105. ; 235:8-9, s. 365-374
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Tidskriftsartikel (refereegranskat)abstract
- A set of imidazolium-based ionic liquids (ILs), 1-(2-hydroxyethyl)-3-methylimidazolium chloride (1), 1,3-bis-(2-hydroxyethyl)-imidazolium chloride (2), and 1-butyl-2,3,4,5-tetramethylimidazolium bromide (3), has been synthesized and their structural and thermal behavior studied. Organic halides are well-known IL formers with imidazolium halides being the most prominent ones. Functionalization of the imidazolium cation by enhancing its hydrogen bonding capacity, i.e. through introduction of -OH groups or by diminishing it, i.e. through substitution of the ring hydrogen atoms by methyl groups is expected to change the inter-ionic interactions. Consequently, the solid-state structures of 1-3 have been characterized with means of single X-ray diffraction to shed light on preferential inter-ionic interactions for obtaining valuable information on anti-crystal engineering, i.e. designing ion combinations that favor a low melting point and exhibit a low tendency for crystallization. The study reveals that endowing IL forming ions with an enhanced hydrogen bonding capacity leads to a depression in melting points and kinetically hinders crystallization. This study provides hints towards new design concepts for IL design, similar to the common strategy of employing conformationally flexible ions.
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| 7. |
- Schädlich, Philip, et al.
(författare)
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Domain Boundary Formation Within an Intercalated Pb Monolayer Featuring Charge-Neutral Epitaxial Graphene
- 2023
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Ingår i: Advanced Materials Interfaces. - 2196-7350. ; 10:27
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of new graphene-based quantum materials by intercalation is an auspicious approach. However, an accompanying proximity coupling depends crucially on the structural details of the new heterostructure. It is studied in detail the Pb monolayer structure after intercalation into the graphene buffer layer on the SiC(0001) interface by means of photoelectron spectroscopy, x-ray standing waves, and scanning tunneling microscopy. A coherent fraction close to unity proves the formation of a flat Pb monolayer on the SiC surface. An interlayer distance of 3.67 Å to the suspended graphene underlines the formation of a truly van der Waals heterostructure. The 2D Pb layer reveals a quasi ten-fold periodicity due to the formation of a grain boundary network, ensuring the saturation of the Si surface bonds. Moreover, the densely-packed Pb layer also efficiently minimizes the doping influence by the SiC substrate, both from the surface dangling bonds and the SiC surface polarization, giving rise to charge-neutral monolayer graphene. The observation of a long-ranged ((Formula presented.)) reconstruction on the graphene lattice at tunneling conditions close to Fermi energy is most likely a result of a nesting condition to be perfectly fulfilled.
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