| 1. |
- Agirre, Jon, et al.
(författare)
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The CCP4 suite: integrative software for macromolecular crystallography
- 2023
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Ingår i: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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| 2. |
- Bender, Michael, et al.
(författare)
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Future of nuclear fission theory
- 2020
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:11
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Forskningsöversikt (refereegranskat)abstract
- There has been much recent interest in nuclear fission, due in part to a new appreciation of its relevance to astrophysics, stability of superheavy elements, and fundamental theory of neutrino interactions. At the same time, there have been important developments on a conceptual and computational level for the theory. The promising new theoretical avenues were the subject of a workshop held at the University of York in October 2019; this report summarises its findings and recommendations.
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| 3. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 4. |
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| 5. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 6. |
- Pascoal, Tharick A, et al.
(författare)
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Microglial activation and tau propagate jointly across Braak stages.
- 2021
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 27, s. 1592-1599
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Tidskriftsartikel (refereegranskat)abstract
- Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer's disease (AD). We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain. We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([11C]PBR28), amyloid-β (Aβ) ([18F]AZD4694) and tau ([18F]MK-6240) pathologies. We further assessed microglial triggering receptor expressed on myeloid cells 2 (TREM2) cerebrospinal fluid (CSF) concentrations and brain gene expression patterns. We found that [11C]PBR28 correlated with CSF soluble TREM2 and showed regional distribution resembling TREM2 gene expression. Network analysis revealed that microglial activation and tau correlated hierarchically with each other following Braak-like stages. Regression analysis revealed that the longitudinal tau propagation pathways depended on the baseline microglia network rather than the tau network circuits. The co-occurrence of Aβ, tau and microglia abnormalities was the strongest predictor of cognitive impairment in our study population. Our findings support a model where an interaction between Aβ and activated microglia sets the pace for tau spread across Braak stages.
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| 7. |
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| 8. |
- Akiba, K., et al.
(författare)
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LHC forward physics
- 2016
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 43:11
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Beckmann, Holger, et al.
(författare)
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Spectral sensitivity in Onychophora (velvet worms) revealed by electroretinograms, phototactic behaviour and opsin gene expression.
- 2015
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 218:6, s. 915-922
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Tidskriftsartikel (refereegranskat)abstract
- Onychophorans typically possess a pair of simple eyes, inherited from the last common ancestor of Panarthropoda (Onychophora + Tardigrada + Arthropoda). These visual organs are thought to be homologous to the arthropod median ocelli, whereas the compound eyes most likely evolved in the arthropod lineage. To gain insights into the ancestral function and evolution of the visual system in panarthropods, we investigated phototactic behaviour, opsin gene expression and the spectral sensitivity of the eyes in two representative species of Onychophora: Euperipatoides rowelli (Peripatopsidae), and Principapillatus hitoyensis (Peripatidae). Our behavioural analyses, in conjunction with previous data, demonstrate that both species exhibit photonegative responses to wavelengths ranging from ultraviolet to green light (370-530 nm), while electroretinograms reveal that the onychophoran eye is maximally sensitive to blue light (peak sensitivity ~480 nm). Template fits to the obtained sensitivities suggest that the onychophoran eye is monochromatic. To clarify on which type of opsin the single visual pigment is based, we localised the corresponding mRNA in the onychophoran eye and brain using in situ hybridization. Our data show that the r-opsin gene (onychopsin) is expressed exclusively in the photoreceptor cells of the eye, whereas the c-opsin mRNA is confined to optic ganglion cells and the brain. Together, our findings suggest that the onychopsin is involved in vision, whereas the c-opsin might have a photoreceptive, non-visual function in onychophorans.
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| 10. |
- Bianco, L., et al.
(författare)
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Discovery of W-157 and Os-161
- 2010
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 690:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- The nuclides W-157 and Os-161 have been discovered ill reactions of Ni-58 ion beams with a Cd-106 target. The Os-161 alpha-decay energy and half-life were 6890 +/- 12 keV and 640 +/- 60 mu s. The daughter W-157 nuclei beta-decayed with a half-life of 275 +/- 40 ms, populating both low-lying alpha-decaying states in Ta-157, which is consistent with a 7/2(-) ground state in W-157. Fine structure observed in the alpha decay of Os-161 places the lowest excited state in W-157 with 1(pi) = 9/2(-) at 318 +/- 30 key. The branching ratio of 5.5(-2.2)(+3.1)% indicates that Os-161 also has a 7/2(-) ground state. Shell-model calculations analysing the effects of monopole shifts and a tensor force on the relative energies of 2f(7/2) and 1h(9/2) neutron states in N = 83 isotones are presented. (C) 2010 Elsevier B.V. All rights reserved.
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| 11. |
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| 12. |
- Delfabbro, Paul, et al.
(författare)
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Who is doing well : Age 15 predictors of psychological and physical health in young adulthood
- 2019
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Ingår i: Australian psychologist. - : Informa UK Limited. - 0005-0067 .- 1742-9544. ; 54:2, s. 114-124
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAccording to Diener (1984), wellbeing is a multi-faceted concept reflecting satisfaction with life, good physical health, and fewer negative psychological symptoms. Using data from a 10-year longitudinal study of school leavers (n = 390), we examine whether people aged 25 can be differentiated into clusters based on indicators of wellbeing, then whether membership in the healthy as opposed to the less healthy cluster can be predicted by age 15 variables.MethodTested predictor variables at age 15 captured the major influences in Bronfenbrenner's Ecological Theory (1979) including individual, family, and social influences. Young adults (age 25) were differentiated into two clusters based on indicators of mental health and subjective wellbeing.ResultsPoorer health, self-image, family functioning, and peer relations at age 15 predicted poorer overall wellbeing at age 25.ConclusionsResults underscore the potential value of psychological support for adolescents within the school environment and the early identification of individuals at risk of problems which may persist into adulthood.
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| 13. |
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| 14. |
- Imperial, Julita S., et al.
(författare)
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Venomous auger snail Hastula (Impages) hectica (Linnaeus, 1758): Molecular phylogeny, foregut anatomy and comparative toxinology
- 2007
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Ingår i: Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. - : Wiley. - 1552-5007 .- 1552-5015. ; 308B:6, s. 744-756
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Tidskriftsartikel (refereegranskat)abstract
- The > 10,000 living venomous marine snail species [superfamily Conoidea Fleming, 1822] include cone snails (Conus), the overwhelming focus of research. Hastula hectica (Linnaeus, 1758), a venomous snail in the family Terebridae Morch, 1852 was comprehensively investigated. The Terebridae comprise a major monophyletic group within Conoidea. H. hectica has a striking radular tooth to inject venom that looks like a perforated spear; in Conus, the tooth looks like a hypodermic needle. H. hectica venom contains a large complement of small disulfide-rich peptides, but with no apparent overlap with Conus in gene superfamilies expressed. Although Conus peptide toxins are densely post-translationally modified, no post-translationally modified amino acids were found in any Hastula venom peptide. The results suggest that different major lineages of venomous molluscs have strikingly divergent toxinological and venom-delivery strategies. J. Exp. Zool. (Mol. Deu. Euol.) 308B: 744- 756, 2007. (c) 2007 Wiley-Liss, Inc.
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| 15. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 16. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 17. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 18. |
- Mayer, Georg, et al.
(författare)
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Evolution of pigment-dispersing factor neuropeptides in panarthropoda : Insights from onychophora (Velvet Worms) and tardigrada (Water Bears)
- 2015
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 523:13, s. 1865-1885
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Tidskriftsartikel (refereegranskat)abstract
- Pigment-dispersing factor (PDF) denotes a conserved family of homologous neuropeptides present in several invertebrate groups, including mollusks, nematodes, insects and crustaceans (referred to here as pigment-dispersing hormone, PDH). Regarding their encoding genes (pdf, pdh), insects possess only one, nematodes two, and decapod crustaceans up to three, but their phylogenetic relationship is unknown. To shed light on the origin and diversification of pdf/pdh homologs in Panarthropoda (Onychophora + Tardigrada + Arthropoda) and other molting animals (Ecdysozoa), we analyzed the transcriptomes of five distantly related onychophorans and a representative tardigrade and searched for putative pdf homologs in publically available genomes of other protostomes. This revealed only one pdf homolog in several mollusk and annelid species, two in Onychophora, Priapulida and Nematoda, and three in Tardigrada. Phylogenetic analyses suggest that the last common ancestor of Panarthropoda possessed two pdf homologs, one of which was lost in the arthropod or arthropod/tardigrade lineage, followed by subsequent duplications of the remaining homolog in some taxa. Immunolocalization of PDF-like peptides in six onychophoran species, using a broadly reactive antibody that recognizes PDF/PDH peptides in numerous species, revealed an elaborate system of neurons and fibers in their central and peripheral nervous systems. Large varicose projections in the heart suggest that the PDF neuropeptides functioned as both circulating hormones and locally released transmitters in the last common ancestor of Onychophora and Arthropoda. The lack of PDF-like immunoreactive somata associated with the onychophoran optic ganglion conforms to the hypothesis that onychophoran eyes are homologous to the arthropod median ocelli.
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| 19. |
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| 20. |
- Sarin, Nikhil, et al.
(författare)
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Linking the rates of neutron star binaries and short gamma-ray bursts
- 2022
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Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 105:8
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Tidskriftsartikel (refereegranskat)abstract
- Short gamma-ray bursts are believed to be produced by both binary neutron star (BNS) and neutron star-black hole (NSBH) mergers. We use current estimates for the BNS and NSBH merger rates to calculate the fraction of observable short gamma-ray bursts produced through each channel. This allows us to constrain merger rates of a BNS to R-BNS = 384(-213)(+431) Gpc(-3) yr(-1) (90% credible interval), a 16% decrease in the rate uncertainties from the second Laser Interferometer Gravitational Wave Observatory (LIGO)-Virgo Gravitational-Wave Transient Catalog. Assuming a top-hat emission profile with a large Lorentz factor, we constrain the average opening angle of gamma-ray burst jets produced in BNS mergers to approximate to 15 degrees. We also measure the fraction of BNS and NSBH mergers that produce an observable short gamma-ray burst to be 0.02(-0.01)(+0.02) and 0.01 +/- 0.01, respectively, and find that greater than or similar to 40% of BNS mergers launch jets (90% confidence). We forecast constraints for future gravitational-wave detections given different modeling assumptions, including the possibility that BNS and NSBH jets are different. With 24 BNS and 55 NSBH observations, expected within six months of the LIGO-Virgo-Kamioka Gravitational Wave Detector network operating at design sensitivity, it will be possible to constrain the fraction of BNS and NSBH mergers that launch jets with 10% precision. Within a year of observations, we can determine whether the jets launched in NSBH mergers have a different structure than those launched in BNS mergers and rule out whether greater than or similar to 80% of binary neutron star mergers launch jets. We discuss the implications of future constraints on understanding the physics of short gamma-ray bursts and binary evolution.
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| 21. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 22. |
- Schaffer Aguzzoli, Cristiano, et al.
(författare)
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Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease
- 2023
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Ingår i: JAMA network open. - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms. Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum. Design, Setting, and Participants: This cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions. Main Outcomes and Measures: All individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET). Results: Of the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β=7.37; 95% CI, 1.34-13.41; P=.01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β=6.86; 95% CI, 1.77-11.95; P=.008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β=5.72; 95% CI, 0.33-11.10; P=.03). Conclusions and Relevance: In this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.
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| 23. |
- Stevenson, Bradley S, et al.
(författare)
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Hoeflea anabaenae sp. nov., an epiphytic symbiont that attaches to the heterocysts of a strain of Anabaena.
- 2011
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Ingår i: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5034 .- 1466-5026. ; 61:10, s. 2439-2444
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Tidskriftsartikel (refereegranskat)abstract
- The heterotrophic, epiphytic symbiotic bacterial strain WH2K(T) was previously isolated from a two-member culture in which it was attached to the heterocysts of a strain of Anabaena (SSM-00). Analysis of its 16S rRNA genes demonstrated that the symbiont was most closely related to the type strain of Hoeflea marina (96.9% similarity), which belongs to the family Phyllobacteriaceae within the order Rhizobiales of the class Alphaproteobacteria. A polyphasic taxonomic study was performed on strain WH2K(T) that consisted of irregular rods (2-5μm long, 0.2μm wide) that appeared to be narrower at one polar end. Optimal growth was obtained in complex media with 15 g l(-1) sea salts, at 18-34 °C (30 °C optimum) and at pH values in the range of 6.0-8.0 (6.5 optimum). Unknown growth requirements were provided by small amounts of yeast extract but not standard vitamin and trace metal solutions. Of the substrates tested, WH2K(T) was only able to utilize acetate, pyruvate, malate, and fumarate. Growth was only observed under aerobic and microaerobic conditions and nitrate was not reduced. No photosynthetic pigments were detected under any of the growth conditions tested. The predominant fatty acids were present in a summed feature that comprises C (18:1) ω7c, / 9t /12t or any combination of these (64.0%) and an unidentified fatty acid of estimated chain length (ECL of C(17.6) (13.5%), The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphoglycolipid, unknown lipids and an unidentified aminolipid. The only respiratory ubiquinone detected was Q-10. The DNA %G+C content of the strain is 58.1%. The organism can form a site-specific attached symbiotic relationship with a species of Anabaena. Based on phylogenetic and phenotypic evidence it is proposed that strain WH2K(T) be classified as a fourth species of the genus Hoeflea, for which the name Hoeflea anabaenae sp. nov. is proposed. The type strain of Hoeflea anabaenae sp. nov. is WH2K(T) (=CCUG 56626(T) =NRRL B-59520(T)).
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| 24. |
- Stevenson-Hoare, Joshua, et al.
(författare)
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Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease.
- 2023
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 146:2, s. 690-699
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Tidskriftsartikel (refereegranskat)abstract
- Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer's disease with biomarkers rather than clinical assessment, we assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer's disease instead of the risk of dementia. In a cohort of Alzheimer's disease cases (N=1439, mean age 68 years [SD=8.2]) and screened controls (N=508, mean age 82 years [SD=6.8]), we measured plasma concentrations of the 40 and 42 amino acid-long amyloid β fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) using state-of-the-art Single molecule array (Simoa) technology. We tested the relationships between the biomarkers and Alzheimer's disease genetic risk, age at onset, and disease duration. We also conducted a genome-wide association study for association of disease risk genes with these biomarkers. The prediction accuracy of Alzheimer's disease clinical diagnosis by the combination of all biomarkers, APOE and polygenic risk score reached AUC=0.81, with the most significant contributors being ε4, Aβ40 or Aβ42, GFAP and NfL. All biomarkers were significantly associated with age in cases and controls (p<4.3x10-5). Concentrations of the Aβ-related biomarkers in plasma were significantly lower in cases compared with controls, whereas other biomarker levels were significantly higher in cases. In the case-control genome-wide analyses, APOE-ε4 was associated with all biomarkers (p=0.011- 4.78x10-8), except NfL. No novel genome-wide significant SNPs were found in the case-control design; however, in a case-only analysis, we found two independent genome-wide significant associations between the Aβ42/Aβ40 ratio and WWOX and COPG2 genes. Disease prediction modelling by the combination of all biomarkers indicates that the variance attributed to P-tau181 is mostly captured by APOE-ε4, whereas Aβ40, Aβ42, GFAP and NfL biomarkers explain additional variation over and above APOE. We identified novel plausible genome wide-significant genes associated with Aβ42/Aβ40 ratio in a sample which is fifty times smaller than current genome-wide association studies in Alzheimer's disease.
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| 25. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 26. |
- Therriault, Joseph, et al.
(författare)
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Association of Phosphorylated Tau Biomarkers With Amyloid Positron Emission Tomography vs Tau Positron Emission Tomography.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:2, s. 188-99
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Tidskriftsartikel (refereegranskat)abstract
- The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-β plaques and tau neurofibrillary tangles.To determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral β-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET).This was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau181, p-tau217, p-tau231, p-tau235), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau181, p-tau217, p-tau231), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau181, [18F]florbetapir PET, and [18F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging/PET safety contraindications. No participants who met eligibility criteria were excluded.Amyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay.Associations between p-tau biomarkers with amyloid PET and tau PET.A total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P=.006; p-tau217 difference, 11%; 95% CI, 3%-20%; P=.003; p-tau231 difference, 15%; 95% CI, 5%-22%; P<.001; p-tau235 difference, 9%; 95% CI, 1%-19%; P=.02) . These results were replicated with plasma p-tau181 (difference, 11%; 95% CI, 1%-22%; P=.02), p-tau217 (difference, 9%; 95% CI, 1%-19%; P=.02), p-tau231 (difference, 13%; 95% CI, 3%-24%; P=.009), and CSF p-tau181 (difference, 9%; 95% CI, 1%-21%; P=.02) in independent cohorts.Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework.
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| 27. |
- Therriault, Joseph, et al.
(författare)
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Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology
- 2024
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Ingår i: Molecular Neurodegeneration. - 1750-1326. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181, p-tau217 and p-tau231 with established immunoassay techniques. Methods: We measured p-tau181, p-tau217 and p-tau231 concentrations in CSF from 173 participants from the TRIAD cohort and 394 participants from the BioFINDER-2 cohort using both mass spectrometry and immunoassay methods. All subjects were clinically evaluated by dementia specialists and had amyloid-PET and tau-PET assessments. Bland–Altman analyses evaluated the agreement between immunoassay and mass spectrometry p-tau181, p-tau217 and p-tau231. P-tau associations with amyloid-PET and tau-PET uptake were also compared. Receiver Operating Characteristic (ROC) analyses compared the performance of mass spectrometry and immunoassays p-tau concentrations to identify amyloid-PET positivity. Results: Mass spectrometry and immunoassays of p-tau217 were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau181 and p-tau231 concentrations measured using antibody-free mass spectrometry had lower performance compared with immunoassays. Conclusions: Our results suggest that while similar overall, immunoassay-based p-tau biomarkers are slightly superior to antibody-free mass spectrometry-based p-tau biomarkers. Future work is needed to determine whether the potential to evaluate multiple biomarkers within a single run offsets the slightly lower performance of antibody-free mass spectrometry-based p-tau quantification.
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| 28. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 29. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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