| 1. |
- Schijven, Dick, et al.
(författare)
-
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
-
Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
|
|
| 2. |
- Dorst, Johannes, et al.
(författare)
-
Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 90
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The emergence of potentially effective new therapies for genetic forms of amyotrophic lateral sclerosis (ALS) necessitates the identification of biomarkers to facilitate early treatment, prior to the onset of motor symptoms. Here, we sought to investigate whether metabolic alterations are detectable in presymptomatic ALS gene mutation carriers, and whether such alterations precede neurofilament light chain (NfL) changes in serum.Methods: Between 02/2014 and 11/2021, we prospectively studied 60 presymptomatic ALS gene mutation carriers (40% male, age 48.7 ± 14.9; 28 C9orf72, 22 SOD1, 10 other) compared to 73 individuals from the same families (47% male, age 47.4 ± 12.9) without pathogenic mutations as controls. Bioimpedance analysis (BIA) and indirect calorimetry were performed, and Body Mass Index (BMI), Fat Mass (FM), Body Fat Percentage, Body Water (BW), Lean Body Mass (LBM), Extracellular Mass (ECM), Body Cell Mass (BCM), ECM/BCM ratio, Cells Percentage, Phase Angle, Resting Metabolic Rate (RMR), Metabolic Ratio (MR), and NfL were measured. Participants and evaluators were blinded regarding gene carrier status.Findings: Presymptomatic ALS gene carriers showed reduced LBM (p = 0.02), BCM (p = 0.004), Cells Percentage (p = 0.04), BW (p = 0.02), Phase Angle (p = 0.04), and increased ECM/BCM ratio (p = 0.04), consistently indicating a loss of metabolically active body cells. While in C9orf72 mutation carriers all tissue masses were reduced, only metabolically active tissue was affected in SOD1 mutation carriers. Unexpectedly, RMR (p = 0.009) and MR (p = 0.01) were lower in presymptomatic ALS gene carriers compared to non-carriers. NfL serum levels were similar in mutation carriers and non-carriers (p = 0.60).Interpretation: The observed metabolic phenomena might reflect reduced physical activity and/or preemptive, insufficient compensatory mechanisms to prepare for the later hypermetabolic state. As pre-symptomatic biomarkers we propose ECM/BCM ratio and Phase Angle for SOD1, and a 4-compartment affection in BIA for C9orf72 mutation carriers.
|
|
| 3. |
|
|
| 4. |
- Haubold, Thorben, et al.
(författare)
-
How Phosphorous Flame Retardant Additives Affect Benzoxazine-Based Monomer and Polymer Properties
- 2023
-
Ingår i: Macromolecular materials and engineering. - : John Wiley and Sons Inc. - 1438-7492 .- 1439-2054. ; 308:11
-
Tidskriftsartikel (refereegranskat)abstract
- The phosphorous-based flame retardant additives poly(m-phenylene methylphosphonate) (PMP) and resorcinol bis(diphenyl phosphate) (RDP) are reacted with bisphenol F and aniline–based benzoxazine (BF-a). DSC, rheological analysis, FT-IR, and soxhlet extraction reveal the covalent incorporation of both FR additives—initiating phenols in PMP structure as well as free phenols generated via transesterification reaction in the case of RDP. In contrast to PMP, RDP elongates the processing window but decreases the thermo–mechanical properties. Both additives increase the resistance in reactions against small flames with solely a phosphorous loading of 0.3 wt%, resulting in a V-0 rating and an improvement in the OI value by up to 2% for RDP and 4% for PMP. Both FRs reduce the heat release rate but increase the smoke production and the smoke toxicity in the case of RDP.
|
|
| 5. |
- Kessler, Thorsten, et al.
(författare)
-
Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
- 2019
-
Ingår i: Cardiovascular Research. - : OXFORD UNIV PRESS. - 0008-6363 .- 1755-3245. ; 115:10, s. 1512-1518
-
Tidskriftsartikel (refereegranskat)abstract
- Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.
|
|
| 6. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 7. |
|
|
| 8. |
- Wolter, Nick, et al.
(författare)
-
Carbon, glass and basalt fiber reinforced polybenzoxazine : The effects of fiber reinforcement on mechanical, fire, smoke and toxicity properties
- 2020
-
Ingår i: Polymers. - : MDPI AG. - 2073-4360. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Bisphenol F and aniline-based benzoxazine monomers were selected to fabricate basalt, glass and carbon fiber reinforced polybenzoxazine via vacuum infusion, respectively. The impacts of the type of fiber reinforcement on the resulting material properties of the fiber reinforced polymers (FRPs) were studied. FRPs exhibited a homogenous morphology with completely impregnated fibers and near-zero porosity. Carbon fiber reinforced polybenzoxazine showed the highest specific mechanical properties because of its low density and high modulus and strength. However, regarding the flammability, fire, smoke and toxicity properties, glass and basalt reinforced polybenzoxazine outperformed carbon fiber reinforced polybenzoxazine. This work offers a deeper understanding of how different types of fiber reinforcement affect polybenzoxazinebased FRPs and provides access to FRPs with inherently good fire, smoke and toxicity performance without the need for further flame retardant additives. © 2020 by the authors.
|
|
| 9. |
- Wolter, Nick, et al.
(författare)
-
Effects of flame-retardant additives on the manufacturing, mechanical, and fire properties of basalt fiber-reinforced polybenzoxazine
- 2021
-
Ingår i: Polymer Engineering and Science. - : John Wiley and Sons Inc. - 0032-3888 .- 1548-2634. ; 61:2, s. 551-561
-
Tidskriftsartikel (refereegranskat)abstract
- Basalt fiber-reinforced polybenzoxazines (BFRP) were manufactured through vacuum infusion using resorcinol bis (diphenyl phosphate) and poly-(m-phenylene methylphosphonate) together with bisphenol-F and aniline based benzoxazine. Different types and loadings of flame-retardant additives showed to have catalysis or dilution effects in viscosity measurements. BFRPs show well-penetrated fibers and near-zero porosity. Additive addition did not influence tensile properties, while apparent interlaminar shear strength decreased indicating a lower adhesion between fiber and matrix. BFRP's heat and smoke release properties increased, though time to ignition increased and flammability behavior improved by decreasing delamination yielding oxygen indices in between 72 and 91%. © 2020 The Authors.
|
|
| 10. |
- Yilmazer-Hanke, Deniz, et al.
(författare)
-
Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts
- 2020
-
Ingår i: Acta neuropathologica communications. - : Springer Nature. - 2051-5960. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.
|
|
