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Sökning: WFRF:(Delarue M)

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  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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  • Janssen, O., et al. (författare)
  • Characteristics of subjective cognitive decline associated with amyloid positivity
  • 2022
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1832-1845
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
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  • Bethlehem, RAI, et al. (författare)
  • Brain charts for the human lifespan
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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  • Boerjan, W., et al. (författare)
  • Superroot, a recessive mutation in Arabidopsis, confers auxin overproduction
  • 1995
  • Ingår i: The Plant Cell. - : JSTOR. - 1040-4651 .- 1532-298X. ; 7:9, s. 1405-1419
  • Tidskriftsartikel (refereegranskat)abstract
    • We have isolated seven allelic recessive Arabidopsis mutants, designated superroot (sur1-1 to sur1-7), displaying several abnormalities reminiscent of auxin effects. These characteristics include small and epinastic cotyledons, an elongated hypocotyl in which the connection between the stele and cortical and epidermal cells disintegrates, the development of excess adventitious and lateral roots, a reduced number of leaves, and the absence of an inflorescence. When germinated in the dark, sur1 mutants did not develop the apical hook characteristic of etiolated seedlings, We were able to phenocopy the Sur1(-) phenotype by supplying auxin to wild-type seedlings, to propagate sur7 explants on phytohormone-deficient medium, and to regenerate shoots from these explants by the addition of cytokinins alone to the culture medium. Analysis by gas chromatography coupled to mass spectrometry indicated increased levels of both free and conjugated indole-3-acetic acid. sur1 was crossed to the mutant axr2 and the altered-auxin response mutant ctr1. The phenotype of both double mutants was additive. The sur1 gene was mapped on chromosome 2 at 0.5 centimorgans from the gene encoding phytochrome B.
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  • Seo, M., et al. (författare)
  • Higher activity of an aldehyde oxidase in the auxin-overproducing superroot1 mutant of Arabidopsis thaliana
  • 1998
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 116:2, s. 687-693
  • Tidskriftsartikel (refereegranskat)abstract
    • Aldehyde oxidase (AO; EC 1.2.3.1) activity was measured in seedlings of wild type or an auxin-overproducing mutant, superroot1 (sur1), of Arabidopsis thaliana. Activity staining for AO after native polyacrylamide gel electrophoresis separation of seedling extracts revealed that there were three major bands with AO activity (AO1-3) in wild-type and mutant seedlings. One of them (AO1) had a higher substrate preference for indole-3-aldehyde. This AO activity was significantly higher in sur1 mutant seedlings than in the wild type. The difference in activity was most apparent 7 d after germination, the same time required for the appearance of the remarkable sur1 phenotype, which includes epinastic cotyledons, elongated hypocotyls, and enhanced root development. Higher activity was observed in the root and hypocotyl region of the mutant seedlings. We also assayed the indole-3-acetaldehyde oxidase activity in extracts by high-performance liquid chromatography detection of indole-3-acetic acid (IAA). The activity was about 5 times higher in the extract of the sur1 seedlings, indicating that AO1 also has a substrate preference for abscisic aldehyde. Treatment of the wild-type seedlings with picloram or IAA caused no significant increase in AO1 activity. This result suggested that the higher activity of AO1 in sur1 mutant seedlings was not induced by IAA accumulation and, thus, strongly supports the possible role of AO1 in IAA biosynthesis in Arabidopsis seedlings.
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  • Delarue, M., et al. (författare)
  • cristal mutations in Arabidopsis confer a genetically heritable, recessive, hyperhydric phenotype
  • 1997
  • Ingår i: Planta. - : Springer Science and Business Media LLC. - 0032-0935 .- 1432-2048. ; 202:1, s. 51-61
  • Tidskriftsartikel (refereegranskat)abstract
    • A new class of recessive Arabidopsis mutants, designated cristal (cii) has been isolated which display several abnormalities reminiscent of hyperhydric symptoms. These characteristics include translucent and wrinkled cotyledons and leaves, abnormal chloroplast organization, a reduced amount of chlorophyll, a reduced dry weight and a decreased number of palisade cells in the leaves accompanied by an increase of intercellular space, and therefore give a vitreous appearance to the aerial part. The phenotype is also dependent on the culture medium water potential. The cril gene was mapped on chromosome 4 close to the DHS1 marker.
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  • Delarue, M., et al. (författare)
  • Sur2 mutations of Arabidopsis thaliana define a new locus involved in the control of auxin homeostasis
  • 1998
  • Ingår i: The Plant Journal. - 0960-7412 .- 1365-313X. ; 14:5, s. 603-611
  • Tidskriftsartikel (refereegranskat)abstract
    • A new auxin homeostasis gene in Arabidopsis called SUR2 has been identified. This gene, mapped to the bottom of chromosome 4, is defined by two recessive nuclear mutants designated superroot2 (sur2), which display several abnormalities reminiscent of auxin effects. A number of these characteristics are similar to the phenotype of the previously described auxin-overproducing mutant superroot1 (sur1); however, several lines of evidences reveal that the SUR2 gene defines a new key point in the regulation of endogenous auxin concentrations. The phenotype of the sur1 sur2 double mutant is additive. Analysis by gas chromatography coupled to mass spectrometry indicated increased levels of free indole-3-acetic acid correlated with a decreased level of bound auxin in the sur2 mutant. These results suggest that SUR2 may be involved in the control of auxin conjugation.
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  • Santoni, V., et al. (författare)
  • A comparison or two-dimensional electrophoresis data with phenotypical traits in Arabidopsis leads to the identification of a mutant (cri1) that accumulates cytokinins
  • 1997
  • Ingår i: Planta. - : Springer Science and Business Media LLC. - 0032-0935 .- 1432-2048. ; 202:1, s. 62-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Total proteins extracted from developmental mutants of Arabidopsis thaliana (L.) Heyhn, and from wild-type plants cultivated in the presence of various hormones were analyzed by two-dimensional (2-D) gel electrophoresis. Computer analysis of 2-D gels followed by a statistical treatment of data allowed us to build a phenogram that describes the biochemical distances between the different genotypes. Analysis of the 2-D electrophoresis data allowed us to discriminate mutants in agreement with phenotypical and physiological traits. This biochemical analysis helped us to develop a working hypothesis which led us to show that one developmental mutant (cril) overaccumulates cytokinins.
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  • Sytiuk, Anna, et al. (författare)
  • Predicting the structure and functions of peatland microbial communities from Sphagnum phylogeny, anatomical and morphological traits and metabolites
  • 2022
  • Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 110:1, s. 80-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Sphagnum mosses are keystone species in northern peatlands. Notably, they play an important role in peatland carbon (C) cycling by regulating the composition and activity of microbial communities. However, it remains unclear whether information on Sphagnum phylogeny and/or traits-based composition (i.e. anatomical and morphological traits and metabolites) can be used to predict the structure of microbial communities and their functioning. Here we evaluated whether Sphagnum phylogeny and traits predict additional variation in peatland microbial community composition and functioning beyond what would be predicted from environmental characteristics (i.e. climatic and edaphic conditions).We collected Sphagnum and microbial data from five European peatlands distributed along a latitudinal gradient from northern Sweden to southern France. These data allowed us to assess Sphagnum anatomical and morphological traits and metabolites at different sites along changing environmental conditions. Using structural equation modelling (SEM) and phylogenetic distance analyses, we investigated the role of Sphagnum traits in shaping microbial community composition and functioning along with environmental conditions.We show that microbial community composition and traits varied independently from both Sphagnum phylogeny and the latitudinal gradient. Specifically, the addition of Sphagnum traits to climatic and edaphic variables to the SEM allowed it to explain a larger proportion of the explained variance (R2). This observation was most apparent for the biomass of decomposers (+42%) and phototrophs (+19%), as well as for growth yield microbial traits (+10%). As such, that Sphagnum metabolites were important drivers for microbial community structure and traits, while Sphagnum anatomical and morphological traits were poor predictors.Synthesis. Our results highlight that Sphagnum metabolites are more likely to influence peatland microbial food web structure and functioning than Sphagnum anatomical and morphological traits. We provide further evidence that measurements of the plant metabolome, when combined with classical functional traits, improve our understanding of how the plants interact with their associated microbiomes.
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  • Delarue, M., et al. (författare)
  • Increased auxin efflux in the IAA-overproducing sur1 mutant of Arabidopsis thaliana: A mechanism for reducing auxin levels?
  • 1999
  • Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317 .- 1399-3054. ; 107:1, s. 120-127
  • Tidskriftsartikel (refereegranskat)abstract
    • With the aim of investigating the mechanisms that maintain auxin homeostasis in plants, we have monitored the net uptake and metabolism of exogenously supplied indole-3-acetic acid (IAA) and naphthalene-1-acetic acid (NAA) in seedlings of wild type and the IAA-overproducing mutant sur1 of Arabidopsis thaliana. Tritiated IAA and NAA entered the seedling tissues within minutes and were mostly accumulated as metabolites, probably amino acid and sugar conjugates, The mutant seedlings were marked by a strong increase of [H-3]IAA metabolism and a reduction of the accumulation levels of both free [H-3]IAA and [H-3]NAA. The same characteristics were observed in wild-type seedlings grown on 5 mu M picloram. We measured [H-3]NAA uptake in the presence of high concentrations of unlabeled NAA or the auxin efflux carrier inhibitor naphthylphthalamic acid (NPA). This abolished the difference in free [H-3]NAA accumulation between the mutant or picloram-treated seedlings and wild-type seedlings. These data indicated that active auxin efflux carriers were present in Arabidopsis seedling tissues. Picloram-treated seedlings and seedlings of the IAA-overproducing mutant sur1 displayed increased auxin efflux carrier activity as well as elevated conjugation of IAA. There is previous evidence to suggest that conjugation is a means to remove excess IAA in plant cells. Here, we discuss the possibility of efflux constituting an additional mechanism for regulating free IAA levels in the face of an excess auxin supply.
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  • Mollier, P., et al. (författare)
  • Promoterless GUS expression in a large number of Arabidopsis thaliana transformants obtained by the in planta infiltration method
  • 1995
  • Ingår i: Comptes rendus de l'Académie des sciences. Série 3, Sciences de la vie. - 0764-4469 .- 1878-5565. ; 318:4, s. 465-474
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of Arabidopsis thaliana transformant T2 families were obtained using in planta infiltration method. A T-DNA containing 2 resistance genes for the selection of the transformants and the promoterless gus gene for promoter-trapping was transferred from the Agrobacterium cells to the plant genome. The GUS activity of each transformant was tested histochemically an 15-day-old seedlings grown in vitro either under light or dark conditions. For each transformant, the GUS activity spatial pattern in plant organs and tissues and the light influence on the GUS activity were studied. Vast variation of GUS activity spatial patterns was observed. A majority of transformants displayed a strictly light-dependent GUS activity Lastly, it was seen that certain transformants could give variable GUS patterns at different stages of development. These spatial, temporal and light-dependent GUS activity features allowed us to characterize the activity of the putative corresponding promoter.
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  • Sytiuk, Anna, et al. (författare)
  • Biochemical traits enhance the trait concept in Sphagnum ecology
  • 2022
  • Ingår i: Oikos. - : John Wiley & Sons. - 0030-1299 .- 1600-0706. ; :4
  • Tidskriftsartikel (refereegranskat)abstract
    • Sphagnum mosses are key to northern peatland carbon sequestration. They have a range of morphological and anatomical characteristics that allow them to cope with environmental stress. Sphagnum also produces a plethora of biochemicals that may prevent stress-induced cell-damage. However, the linkages between Sphagnum anatomical, morphological and biochemical traits (i.e. metabolites, pigments and antioxidant enzyme activities) are poorly known, neither are their joint responses to environmental change. Here, we quantify and link an array of Sphagnum anatomical, morphological and biochemical traits in five Sphagnum-dominated peatlands distributed along a latitudinal gradient in Europe, covering a range of regional and local environmental conditions. Sphagnum morphological and anatomical traits were intrinsically linked to Sphagnum metabolites and enzyme activities, and these relationships were driven by shared responses to local and regional environmental factors. More particularly, we found that Sphagnum traits can be grouped into four clusters related to growth, biomass, defense and water stress tolerance. We used regional and local environmental conditions data to further show that biochemicals and their specific linkages with some morphological traits describe dimensions of physiology not captured by anatomical and morphological traits alone. These results suggest that Sphagnum morphology and function is rooted in the metabolome, and that incorporating biochemicals into the functional trait space concept can enhance our mechanistic understanding and predictive power in Sphagnum ecology.
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