| 1. |
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| 2. |
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| 3. |
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| 4. |
- van Doorn, Ljcv, et al.
(författare)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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| 5. |
- Solana, E, et al.
(författare)
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Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 16805-
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Tidskriftsartikel (refereegranskat)abstract
- The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.
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| 6. |
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| 7. |
- Zumla, A, et al.
(författare)
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Towards host-directed therapies for tuberculosis
- 2015
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 14:8, s. 511-
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Iulita, M. F., et al.
(författare)
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Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome
- 2023
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-beta 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein.4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein.4, female.4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein.4 and biomarkers showed that female.4 carriers tended to exhibit lower CSF amyloid-beta 42/amyloid-beta 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein.4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.
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| 9. |
- Nitschke, S., et al.
(författare)
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Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2361-2377
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Tidskriftsartikel (refereegranskat)abstract
- Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease. This pathology, amylopectinosis, is caused by mutations in a series of single genes whose functions are under active study toward understanding the mechanisms of proper glycogen construction. Concurrently, we are characterizing the physicochemical particularities of glycogen and polyglucosans associated with each gene. These genes include GBE1, EPM2A and EPM2B, which respectively encode the glycogen branching enzyme, the glycogen phosphatase laforin and the laforin-interacting E3 ubiquitin ligase malin, for which an unequivocal function is not yet known. Mutations in GBE1 cause a motor neuron disease (adult polyglucosan body disease), and mutations in EPM2A or EPM2B a fatal progressive myoclonus epilepsy (Lafora disease). RBCK1 deficiency causes an amylopectinosis with fatal skeletal and cardiac myopathy (polyglucosan body myopathy 1, OMIM# 615895). RBCK1 is a component of the linear ubiquitin chain assembly complex, with unique functions including generating linear ubiquitin chains and ubiquitinating hydroxyl (versus canonical amine) residues, including of glycogen. In a mouse model we now show (i) that the amylopectinosis of RBCK1 deficiency, like in adult polyglucosan body disease and Lafora disease, affects the brain; (ii) that RBCK1 deficiency glycogen, like in adult polyglucosan body disease and Lafora disease, has overlong branches; (iii) that unlike adult polyglucosan body disease but like Lafora disease, RBCK1 deficiency glycogen is hyperphosphorylated; and finally (iv) that unlike laforin-deficient Lafora disease but like malin-deficient Lafora disease, RBCK1 deficiency's glycogen hyperphosphorylation is limited to precipitated polyglucosans. In summary, the fundamental glycogen pathology of RBCK1 deficiency recapitulates that of malin-deficient Lafora disease. Additionally, we uncover sex and genetic background effects in RBCK1 deficiency on organ-and brain-region specific amylopectinoses, and in the brain on consequent neuroinflammation and behavioural deficits. Finally, we exploit the portion of the basic glycogen pathology that is common to adult polyglucosan body disease, both forms of Lafora disease and RBCK1 deficiency, namely overlong branches, to show that a unified approach based on downregulating glycogen synthase, the enzyme that elongates glycogen branches, can rescue all four diseases.
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| 10. |
- Rincon, E., et al.
(författare)
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Bioactive pectic polysaccharides from bay tree pruning waste : Sequential subcritical water extraction and application in active food packaging
- 2021
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 272
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Tidskriftsartikel (refereegranskat)abstract
- The potential isolation of bio-active polysaccharides from bay tree pruning waste was studied using sequential subcritical water extraction using different time-temperature combinations. The extracted polysaccharides were highly enriched in pectins while preserving their high molecular mass (10-100 kDa), presenting ideal properties for its application as additive in food packaging. Pectin-enriched chitosan films were prepared, improving the optical properties (>= 95% UV-light barrier capacity), antioxidant capacity (.95% radical scavenging activity) and water vapor permeability (<= 14 g center dot Pa-1 center dot s(-1)center dot m(-1)center dot 10(-7)) in comparison with neat chitosan-based films. Furthermore, the antimicrobial activity of chitosan was maintained in the hybrid films. Addition of 10% of pectins improved mechanical properties, increasing the Young's modulus 12%, and the stress resistance in 51%. The application of pectin-rich fractions from bay tree pruning waste as an additive in active food packaging applications, with triple action as antioxidant, barrier, and antimicrobial has been demonstrated.
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| 11. |
- Rodriguez-Vieitez, E, et al.
(författare)
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Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:12, s. 7813-7822
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Tidskriftsartikel (refereegranskat)abstract
- Noninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer’s disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72.5 [9.4] years; 114 women [58.2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11C-Pittsburgh compound-B-PET, 18F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3.72 (1.96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3.2 (1.7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.
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| 12. |
- Bejanin, A., et al.
(författare)
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Association of Apolipoprotein e ϵ4 Allele with Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults with down Syndrome
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:8, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ϵ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Objective: To investigate the association of the APOE ϵ4 allele with clinical and multimodal biomarkers of AD in adults with DS. Design, Setting, and Participants: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ϵ4 allele carriers or noncarriers. Main Outcomes and Measures: Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ϵ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume. Results: Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ϵ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P =.56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ϵ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P =.02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aβ1-42 to Aβ1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ϵ4 allele carriers. Conclusions and Relevance: In this study, the APOE ϵ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS. © 2021 American Medical Association. All rights reserved.
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| 13. |
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| 14. |
- Berglund, Jennie, et al.
(författare)
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Wood hemicelluloses exert distinct biomechanical contributions to cellulose fibrillar networks
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Hemicelluloses, a family of heterogeneous polysaccharides with complex molecular structures, constitute a fundamental component of lignocellulosic biomass. However, the contribution of each hemicellulose type to the mechanical properties of secondary plant cell walls remains elusive. Here we homogeneously incorporate different combinations of extracted and purified hemicelluloses (xylans and glucomannans) from softwood and hardwood species into self-assembled networks during cellulose biosynthesis in a bacterial model, without altering the morphology and the crystallinity of the cellulose bundles. These composite hydrogels can be therefore envisioned as models of secondary plant cell walls prior to lignification. The incorporated hemicelluloses exhibit both a rigid phase having close interactions with cellulose, together with a flexible phase contributing to the multiscale architecture of the bacterial cellulose hydrogels. The wood hemicelluloses exhibit distinct biomechanical contributions, with glucomannans increasing the elastic modulus in compression, and xylans contributing to a dramatic increase of the elongation at break under tension. These diverging effects cannot be explained solely from the nature of their direct interactions with cellulose, but can be related to the distinct molecular structure of wood xylans and mannans, the multiphase architecture of the hydrogels and the aggregative effects amongst hemicellulose-coated fibrils. Our study contributes to understanding the specific roles of wood xylans and glucomannans in the biomechanical integrity of secondary cell walls in tension and compression and has significance for the development of lignocellulosic materials with controlled assembly and tailored mechanical properties.
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| 15. |
- McKee, Lauren S., et al.
(författare)
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A GH115 alpha-glucuronidase from Schizophyllum commune contributes to the synergistic enzymatic deconstruction of softwood glucuronoarabinoxylan
- 2016
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Ingår i: Biotechnology for Biofuels. - : BioMed Central. - 1754-6834. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lignocellulosic biomass from softwood represents a valuable resource for the production of biofuels and bio-based materials as alternatives to traditional pulp and paper products. Hemicelluloses constitute an extremely heterogeneous fraction of the plant cell wall, as their molecular structures involve multiple monosaccharide components, glycosidic linkages, and decoration patterns. The complete enzymatic hydrolysis of wood hemicelluloses into monosaccharides is therefore a complex biochemical process that requires the activities of multiple degradative enzymes with complementary activities tailored to the structural features of a particular substrate. Glucuronoarabinoxylan (GAX) is a major hemicellulose component in softwood, and its structural complexity requires more enzyme specificities to achieve complete hydrolysis compared to glucuronoxylans from hardwood and arabinoxylans from grasses. Results: We report the characterisation of a recombinant alpha-glucuronidase (Agu115) from Schizophyllum commune capable of removing (4-O-methyl)-glucuronic acid ((Me) GlcA) residues from polymeric and oligomeric xylan. The enzyme is required for the complete deconstruction of spruce glucuronoarabinoxylan (GAX) and acts synergistically with other xylan-degrading enzymes, specifically a xylanase (Xyn10C), an alpha-l-arabinofuranosidase (AbfA), and a beta-xylosidase (XynB). Each enzyme in this mixture showed varying degrees of potentiation by the other activities, likely due to increased physical access to their respective target monosaccharides. The exo-acting Agu115 and AbfA were unable to remove all of their respective target side chain decorations from GAX, but their specific activity was significantly boosted by the addition of the endo-Xyn10C xylanase. We demonstrate that the proposed enzymatic cocktail (Agu115 with AbfA, Xyn10C and XynB) achieved almost complete conversion of GAX to arabinofuranose (Araf), xylopyranose (Xylp), and MeGlcA monosaccharides. Addition of Agu115 to the enzymatic cocktail contributes specifically to 25 % of the conversion. However, traces of residual oligosaccharides resistant to this combination of enzymes were still present after deconstruction, due to steric hindrances to enzyme access to the substrate. Conclusions: Our GH115 alpha-glucuronidase is capable of finely tailoring the molecular structure of softwood GAX, and contributes to the almost complete saccharification of GAX in synergy with other exo- and endo-xylan-acting enzymes. This has great relevance for the cost-efficient production of biofuels from softwood lignocellulose.
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| 16. |
- Moran-Velizquez, Dalia C., et al.
(författare)
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Unravelling Chemical Composition of Agave Spines : News from Agave fourcroydes Lem.
- 2020
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Ingår i: PLANTS. - : MDPI. - 2223-7747. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Spines are key plant modifications developed to deal against herbivores; however, its physical structure and chemical composition have been little explored in plant species. Here, we took advantage of high-throughput chromatography to characterize chemical composition of Agave fourcroydes Lem. spines, a species traditionally used for fiber extraction. Analyses of structural carbohydrate showed that spines have lower cellulose content than leaf fibers (52 and 72%, respectively) but contain more than 2-fold the hemicellulose and 1.5-fold pectin. Xylose and galacturonic acid were enriched in spines compared to fibers. The total lignin content in spines was 1.5-fold higher than those found in fibers, with elevated levels of syringyl (S) and guaiacyl (G) subunits but similar S/G ratios within tissues. Metabolomic profiling based on accurate mass spectrometry revealed the presence of phenolic compounds including quercetin, kaempferol, (+)-catechin, and (-)-epicatechin in A. fourcroydes spines, which were also detected in situ in spines tissues and could be implicated in the color of these plants' structures. Abundance of (+)-catechins could also explain proanthocyanidins found in spines. Agave spines may become a plant model to obtain more insights about cellulose and lignin interactions and condensed tannin deposition, which is valuable knowledge for the bioenergy industry and development of naturally dyed fibers, respectively.
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| 17. |
- Rautio, D, et al.
(författare)
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Validity and reliability of the diagnostic codes for hypochondriasis and dysmorphophobia in the Swedish National Patient Register: a retrospective chart review
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:12, s. e051853-
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Tidskriftsartikel (refereegranskat)abstract
- In the International Classification of Diseases, Tenth Edition (ICD-10), hypochondriasis (illness anxiety disorder) and dysmorphophobia (body dysmorphic disorder) share the same diagnostic code (F45.2). However, the Swedish ICD-10 allows for these disorders to be coded separately (F45.2 and F45.2A, respectively), potentially offering unique opportunities for register-based research on these conditions. We assessed the validity and reliability of their ICD-10 codes in the Swedish National Patient Register (NPR).DesignRetrospective chart review.MethodsSix hundred individuals with a diagnosis of hypochondriasis or dysmorphophobia (300 each) were randomly selected from the NPR. Their medical files were requested from the corresponding clinics, located anywhere in Sweden. Two independent raters assessed each file according to ICD-10 definitions and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and Fifth Edition criteria. Raters also completed the Clinical Global Impression–Severity (CGI-S) and the Global Assessment of Functioning (GAF).Primary outcome measurePer cent between-rater agreement and positive predictive value (PPV). Intraclass correlation coefficients for the CGI-S and the GAF.ResultsEighty-four hypochondriasis and 122 dysmorphophobia files were received and analysed. The inter-rater agreement rate regarding the presence or absence of a diagnosis was 95.2% for hypochondriasis and 92.6% for dysmorphophobia. Sixty-seven hypochondriasis files (79.8%) and 111 dysmorphophobia files (91.0%) were considered ‘true positive’ cases (PPV=0.80 and PPV=0.91, respectively). CGI-S scores indicated that symptoms were moderately to markedly severe, while GAF scores suggested moderate impairment for hypochondriasis cases and moderate to serious impairment for dysmorphophobia cases. CGI-S and GAF inter-rater agreement were good for hypochondriasis and moderate for dysmorphophobia.ConclusionsThe Swedish ICD-10 codes for hypochondriasis and dysmorphophobia are sufficiently valid and reliable for register-based studies. The results of such studies should be interpreted in the context of a possible over-representation of severe and highly impaired cases in the register, particularly for dysmorphophobia.
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| 18. |
- Sullivan, Mitchell A., et al.
(författare)
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Skeletal Muscle Glycogen Chain Length Correlates with Insolubility in Mouse Models of Polyglucosan-Associated Neurodegenerative Diseases
- 2019
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Ingår i: Cell Reports. - : cell press. - 2211-1247. ; 27:5, s. 1334-1344.e6
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Tidskriftsartikel (refereegranskat)abstract
- Lafora disease (LD) and adult polyglucosan body disease (APBD) are glycogen storage diseases characterized by a pathogenic buildup of insoluble glycogen. Mechanisms causing glycogen insolubility are poorly understood. Here, in two mouse models of LD (Epm2a(-/-) and Epm2b(-/-)) and one of APBD (Gbe1(ys/ys)), the separation of soluble and insoluble muscle glycogen is described, enabling separate analysis of each fraction. Total glycogen is increased in LD and APBD mice, which, together with abnormal chain length and molecule size distributions, is largely if not fully attributed to insoluble glycogen. Soluble glycogen consists of molecules with distinct chain length distributions and differential corresponding solubility, providing a mechanistic link between soluble and insoluble glycogen in vivo. Phosphorylation states differ across glycogen fractions and mouse models, demonstrating that hyperphosphorylation is not a basic feature of insoluble glycogen. Lastly, model-specific variances in protein and activity levels of key glycogen synthesis enzymes suggest uninvestigated regulatory mechanisms.
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| 19. |
- Valdés, A., et al.
(författare)
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Gelatin-based antimicrobial films incorporating pomegranate (Punica granatum L.) seed juice by-product
- 2020
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Pomegranate (Punica granatum L.) seed juice by-product (PSP) was added as reinforcing and antimicrobial agent to fish gelatin (FG) films as a promising eco-friendly active material for food packaging applications. A complete linkage analysis of polysaccharides in PSP showed xylan and cellulose as main components. This residue showed also high total phenolic content and antioxidant activity. Three formulations were processed by adding PSP to FG (0, 10, 30 wt. %) by the casting technique, showing films with 10 wt. % of PSP the best performance. The addition of PSP decreased elongation at break and increased stiffness in the FG films, particularly for 30 wt. % loading. A good compatibility between FG and PSP was observed by SEM. No significant (p < 0.05) differences were obtained for barrier properties to oxygen and water vapour permeability compared to the control with the incorporation of PSP, whereas water resistance considerably increased and transparency values decreased (p < 0.05). High thermal stability of films and inhibition against S. aureus were observed. The addition of PSP at 10 wt. % into FG was shown as a potential strategy to maintain the integrity of the material and protect food against lipid oxidation, reducing huge amounts of pomegranate and fish wastes.
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| 20. |
- Vilaplana-Perez, A., et al.
(författare)
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Association of social anxiety disorder with objective indicators of educational attainment : A nation-wide register-based sibling control study
- 2019
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 29:Suppl. 6, s. S150-S151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Social Anxiety Disorder (SAD) is a relatively frequent psychiatric disorder, with a lifetime prevalence of about 4% [1], which usually starts in adolescence [2]. As in the case of other mental disorders, [3] SAD has also been linked to academic impairment and school drop-out [4,5], but this previous research has a number of methodological limitations, mainly the use of modest sample sizes, retrospective designs, self-reported measures, and focusing in a single educational level.Aim: We aim to investigate the association between SAD and educational outcomes at all levels using objectively collected measures, controlling for a number of covariates and unmeasured factors shared between siblings.Method: Using the Swedish nationwide registers, we designed this population-based birth cohort study, which included 2,244,191 individuals born in Sweden between 1973 and 1997, who were followed up from 1991 until 2013. A total of 15,765 individuals had a record of SAD in the Swedish National Patient Register, according to the International Classification of Diseases, 10th edition. Logistic regression models tested the association between SAD and the prospectively-collected and objectively measured educational outcomes. These educational milestones included: the year grades in the final year of compulsory school, the eligibility to access upper secondary school after compulsory education (for both, vocational and academical programs), finishing upper secondary school, starting university, finishing a university degree, and completing post-graduate education. In order to reduce the impact of possible confounders, we took into account a number of covariates such as age, sex, maternal and paternal age at birth and year of birth. The impact of common psychiatric comorbidities of SAD was also taken into account. In order to control for unmeasured shared familial factors, we performed a sibling comparison analysis. We identified 786,766 families with 2 or more siblings, and identified 11,950 families with full siblings discordant for SAD.Results: Compared to the unexposed individuals, individuals with SAD were less likely to pass all subjects in the last year of compulsory school (adjusted odds ratios [aOR] ranging from 0.19 to 0.44). They were also less likely to access a vocational program or an academic program in upper secondary education (aOR=0.31 [95% CI, 0.30–0.33] and aOR=0.52 [95% CI, 0.51–0.55], respectively). SAD cases also had 81% lower odds of finishing upper secondary education (aOR=0.19 [95% CI, 0.19–0.20]), 53% lower odds of starting a university degree (aOR=0.47 [95% CI, 0.45–0.49]), 65% lower odds of finishing a university degree (aOR=0.35 [95% CI, 0.33–0.37]), and 42% lower odds of finishing postgraduate education (aOR=0.58 [95% CI, 0.43-0.80]). Results were attenuated but remained significant in fully adjusted sibling comparison models. When comorbidities were taken into account, results were maintained.Conclusion: SAD has an adverse impact on educational attainment throughout the life-span, even after controlling for confounders and factors shared between siblings.
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| 21. |
- Yilmaz Turan, Secil, et al.
(författare)
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Cascade extraction of proteins and feruloylated arabinoxylans from wheat bran
- 2020
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 333
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Tidskriftsartikel (refereegranskat)abstract
- A cascade process for the sequential recovery of proteins and feruloylated arabinoxylan from wheat bran is proposed, involving a protein isolation step, enzymatic destarching and subcritical water extraction. The protein isolation step combining lactic acid fermentation and cold alkaline extraction reduced the recalcitrance of wheat bran, thus improving the total yields of the subsequent subcritical water extraction. The time evolution of subcritical water extraction of feruloylated arabinoxylan was compared at two temperatures (160 °C and 180 °C). Longer residence times enhanced the purity of target feruloylated arabinoxylans, whereas higher temperatures resulted in faster extraction at the expense of significant molar mass reduction. The radical scavenging activity of the extracted feruloylated arabinoxylans was preserved after the initial protein isolation step. This study opens new possibilities for the cascade valorization of wheat bran into enriched protein and non-starch polysaccharide fractions, which show potential to be used as functional food ingredients.
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