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- Salvado, G., et al.
(författare)
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Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers
- 2019
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Centiloid thresholds that maximize the agreement against core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in two large independent cohorts.MethodsA total of 516 participants of the ALFA+ Study (N=205) and ADNI (N=311) underwent amyloid PET imaging ([F-18]flutemetamol and [F-18]florbetapir, respectively) and core AD CSF biomarker determination using Elecsys (R) tests. Tracer uptake was quantified in Centiloid units (CL). Optimal Centiloid cut-offs were sought that maximize the agreement between PET and dichotomous determinations based on CSF levels of A(42), tTau, pTau, and their ratios, using pre-established reference cut-off values. To this end, a receiver operating characteristic analysis (ROC) was conducted, and Centiloid cut-offs were calculated as those that maximized the Youden's J Index or the overall percentage agreement recorded.ResultsAll Centiloid cut-offs fell within the range of 25-35, except for CSF A(42) that rendered an optimal cut-off value of 12 CL. As expected, the agreement of tau/A(42) ratios was higher than that of CSF A(42). Centiloid cut-off robustness was confirmed even when established in an independent cohort and against variations of CSF cut-offs.ConclusionsA cut-off of 12 CL matches previously reported values derived against postmortem measures of AD neuropathology. Together with these previous findings, our results flag two relevant inflection points that would serve as boundary of different stages of amyloid pathology: one around 12 CL that marks the transition from the absence of pathology to subtle pathology and another one around 30 CL indicating the presence of established pathology. The derivation of robust and generalizable cut-offs for core AD biomarkers requires cohorts with adequate representation of intermediate levels.Trial registrationALFA+ Study, NCT02485730ALFA PET Sub-study, NCT02685969
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- Labriere, C., et al.
(författare)
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Structure-Activity Relationship Probing of the Natural Marine Antifoulant Barettin
- 2021
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Ingår i: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 23:6, s. 904-916
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Tidskriftsartikel (refereegranskat)abstract
- The sponge derived 2,5-diketopiperazine metabolite barettin is a potent antifouling compound effective against the settlement and metamorphosis of barnacles. Simplified derivatives of barettin have previously been shown to display similar inhibitory properties. The synthetic derivative benzo[g]dipodazine has been reported to display significantly improved antifouling properties in comparison with the native barettin with inhibitory activities as low a 0.034 mu M reported against barnacle cyprid settlement. In the current study we report the antifouling activity of 29 synthetic analogs designed and inspired by the potent antifouling effect seen for benzo[g]dipodazine. The library contains mainly not only dipodazine derivatives but also disubstituted diketopiperazines and compounds incorporating alternative heterocyclic cores such as hydantoin, creatinine, and rhodanine. Several of the prepared compounds inhibit the settlement of Amphibalanus improvisus cyprids at low micromolar concentrations, in parity with the natural barettin. While several highly active compounds were prepared by incorporating the benzo[g]indole as hydrophobic substituent, the remarkable antifouling effect reported for benzo[g]dipodazine was not observed when evaluated in our study.
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- Raković, Marko, et al.
(författare)
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Geographic patterns of mtDNA and Z-linked sequence variation in the Common Chiffchaff and the ‘chiffchaff complex’
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The Common Chiffchaff Phylloscopus collybita is an abundant, polytypic Palearctic bird. Validity of some of its subspecies is controversial and birds from some parts of the species range remain unclassified taxonomically. The relationships among populations from different geographic areas have not been sufficiently explored with molecular data. In this study we analyzed the relationships among the four species in the ‘chiffchaff complex’ (Common Chiffchaff, Iberian Chiffchaff P. ibericus, Canary Islands Chiffchaff P. canariensis and Mountain Chiffchaff P. sindianus), and the patterns of intraspecific geographic variation in the mtDNA ND2 gene and intron 9 of the Z-linked aconitase gene (ACO1I9) across the Common Chiffchaff range, including a recently discovered population breeding on Mt. Hermon (Anti-Lebanon mountains). Our data supported the monophyly of the chiffchaff complex and its current systematics at the species level. Within the Common Chiffchaff, the Siberian race P. c. tristis was the most differentiated subspecies and may represent a separate or incipient species. Other Common Chiffchaff subspecies also were differentiated in their mtDNA, however, lineages of neighboring subspecies formed wide zones of introgression. The Mt. Hermon population was of mixed genetic origin but contained some birds with novel unique lineage that could not be assigned to known subspecies. All Common Chiffchaff lineages diverged at the end of the Ionian stage of Pleistocene. Lineage sorting of ACO1I9 alleles was not as complete as that of mtDNA. Chiffchaff species were mostly distinct at ACO1I9, except the Common and Canary Islands Chiffchaffs that shared multiple alleles. An AMOVA identified geographic structure in Common Chiffchaff ACO1I9 variation that was broadly consistent with that of mtDNA ND2 gene. The genetic and other data suggest the chiffchaff complex to be a group of evolutionarily young taxa that represent a paradigm of ‘species evolution in action’ from intergrading subspecies through to apparently complete biological speciation.
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- Visch, Wouter, et al.
(författare)
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Underpinning the Development of Seaweed Biotechnology: Cryopreservation of Brown Algae (Saccharina latissima) Gametophytes
- 2019
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Ingår i: Biopreservation and Biobanking. - : Mary Ann Liebert Inc. - 1947-5535 .- 1947-5543. ; 17:5, s. 378-386
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Tidskriftsartikel (refereegranskat)abstract
- Sugar kelp (Saccharina latissima) is an economically important species, and natural populations provide diverse and productive habitats as well as important ecosystem services. For seaweed aquaculture to be successful in newly emerging industry in Europe and other Western countries, it will have to develop sustainable production management strategies. A key feature in this process is the capacity to conserve genetic diversity for breeding programs aimed at developing seed stock for onward cultivation, as well as in the management of wild populations, as potentially interesting genetic resources are predicted to disappear due to climate change. In this study, the cryopreservation of male and female gametophytes (haploid life stage) of S. latissima by different combinations of two-step cooling methods and cryoprotectants was explored. We report here that cryopreservation constitutes an attractive option for the long-term preservation of S. latissima gametophytes, with viable cells in all treatment combinations. The highest viabilities for both male and female gametophytes were found using controlled-rate cooling methods combined with dimethyl sulfoxide 10% (v/v). Morphological normal sporophytes were observed to develop from cryopreserved vegetative gametophytic cells, independent of treatment. This indicates that cryopreservation is a useful preservation method for male and female S. latissima gametophytes.
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- Barboza, F. R., et al.
(författare)
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Geographic variation in fitness-related traits of the bladderwrack Fucus vesiculosus along the Baltic Sea-North Sea salinity gradient
- 2019
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:16, s. 9225-9238
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Tidskriftsartikel (refereegranskat)abstract
- In the course of the ongoing global intensification and diversification of human pressures, the study of variation patterns of biological traits along environmental gradients can provide relevant information on the performance of species under shifting conditions. The pronounced salinity gradient, co-occurrence of multiple stressors, and accelerated rates of change make the Baltic Sea and its transition to North Sea a suitable region for this type of study. Focusing on the bladderwrack Fucus vesiculosus, one of the main foundation species on hard-bottoms of the Baltic Sea, we analyzed the phenotypic variation among populations occurring along 2,000km of coasts subjected to salinities from 4 to >30 and a variety of other stressors. Morphological and biochemical traits, including palatability for grazers, were recorded at 20 stations along the Baltic Sea and four stations in the North Sea. We evaluated in a common modeling framework the relative contribution of multiple environmental drivers to the observed trait patterns. Salinity was the main and, in some cases, the only environmental driver of the geographic trait variation in F.vesiculosus. The decrease in salinity from North Sea to Baltic Sea stations was accompanied by a decline in thallus size, photosynthetic pigments, and energy storage compounds, and affected the interaction of the alga with herbivores and epibiota. For some traits, drivers that vary locally such as wave exposure, light availability or nutrient enrichment were also important. The strong genetic population structure in this macroalgae might play a role in the generation and maintenance of phenotypic patterns across geographic scales. In light of our results, the desalination process projected for the Baltic Sea could have detrimental impacts on F.vesiculosus in areas close to its tolerance limit, affecting ecosystem functions such as habitat formation, primary production, and food supply.
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