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- Esteve-Raventos, Fernando, et al.
(author)
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A Taxonomic and Phylogenetic Contribution on Inosperma Section Inosperma (Agaricales, Inocybaceae) in Europe: Calamistratum and Geraniodorum Groups
- 2024
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In: JOURNAL OF FUNGI. - 2309-608X. ; 10:6
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Journal article (peer-reviewed)abstract
- The aim of this study is to carry out a taxonomic revision of the groups Calamistratum and Geraniodorum of the genus Inosperma sect. Inosperma in Europe. For this purpose, a multigenic phylogenetic analysis was carried out using the ITS, LSU, RPB1 and RPB2 markers, covering a total of 111 sequences, including those generated from the existing type-material collections. This analysis led to the recognition of nine clades or terminal groups for the European continent, correlating with nine morphological species. Three of them, I. calamistratum, I. neohirsutum sp. nov. and I. turietoense sp. nov., are distributed in humid and temperate forests, whereas I. geminum sp. nov., I. geraniodorum, I. gracilentum sp. nov., I. praetermissum comb. nov., I. subhirsutum and I. veliferum seem to be restricted to the colder altimontane, boreal and alpine climates. It is concluded that the study of morphological and ecological characteristics allows the recognition of species without the need for an often-subjective interpretation of organoleptic characteristics. Inocybe hirsuta is considered a synonym of Inosperma calamistratum, Inosperma praetermissum as a different species from I. calamistratum, and Inocybe geraniodora var. gracilenta f. salicis-herbaceae as a synonym of I. praetermissum. Four new species and one new combination are proposed. A key for the recognition of the European species is provided. Illustrations and photographs of macro- and micromorphological characters and SEM spores of all species are presented.
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| 2. |
- Linnemann, Christoph, et al.
(author)
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NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study
- 2024
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In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - 0022-3050 .- 1468-330X.
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Journal article (peer-reviewed)abstract
- BackgroundBlood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites.MethodsComparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72, GRN or MAPT; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer.ResultsNfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12 +/- 1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model.ConclusionsOur results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.
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| 3. |
- Swift, Imogen J, et al.
(author)
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A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
- 2024
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In: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
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Journal article (peer-reviewed)abstract
- Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
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