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| 4. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 5. |
- Alic, I., et al.
(författare)
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Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10, s. 5766-5788
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Tidskriftsartikel (refereegranskat)abstract
- A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of beta-amyloid-(A beta)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar A beta deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical beta and gamma-secretase inhibition. We found that T21 organoids secrete increased proportions of A beta-preventing (A beta 1-19) and A beta-degradation products (A beta 1-20 and A beta 1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in similar to 30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.
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| 6. |
- Babulal, Ganesh M, et al.
(författare)
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Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.
- 2019
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:2, s. 292-312
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.
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| 7. |
- Portnichenko, P. Y., et al.
(författare)
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Momentum-space structure of quasielastic spin fluctuations in Ce3Pd20Si6
- 2015
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 91:9
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Tidskriftsartikel (refereegranskat)abstract
- Among heavy-fermion metals, Ce3Pd20Si6 is one of the heaviest-electron systems known to date. Here we used high-resolution neutron spectroscopy to observe low-energy magnetic scattering from a single crystal of this compound in the paramagnetic state. We investigated its temperature dependence and distribution in momentum space, which was not accessible in earlier measurements on polycrystalline samples. At low temperatures, a quasielastic magnetic response with a half-width Gamma approximate to 0.1 meV persists with varying intensity all over the Brillouin zone. It forms a broad hump centered at the (111) scattering vector, surrounded by minima of intensity at (002), (220), and equivalent wave vectors. The momentum-space structure distinguishes this signal from a simple crystal-field excitation at 0.31 meV, suggested previously, and rather lets us ascribe it to short-range dynamical correlations between the neighboring Ce ions, mediated by the itinerant heavy f electrons via the Ruderman-Kittel-Kasuya-Yosida mechanism. With increasing temperature, the energy width of the signal follows the conventional T-1/2 law, Gamma(T) = Gamma(0) + A root T. The momentum-space symmetry of the quasielastic response suggests that it stems from the simple-cubic Ce sublattice occupying the 8c Wyckoff site, whereas the crystallographically inequivalent 4a site remains magnetically silent in this material.
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| 8. |
- Pape, S. E., et al.
(författare)
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The reliability and validity of DSM 5 diagnostic criteria for neurocognitive disorder and relationship with plasma neurofilament light in a down syndrome population
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The validity of dementia diagnostic criteria depends on their ability to distinguish dementia symptoms from pre-existing cognitive impairments. The study aimed to assess inter-rater reliability and concurrent validity of DSM-5 criteria for neurocognitive disorder in Down syndrome. The utility of mild neurocognitive disorder as a distinct diagnostic category, and the association between clinical symptoms and neurodegenerative changes represented by the plasma biomarker neurofilament light were also examined. 165 adults with Down syndrome were included. Two clinicians independently applied clinical judgement, DSM-IV, ICD-10 and DSM-5 criteria for dementia (or neurocognitive disorder) to each case. Inter-rater reliability and concurrent validity were analysed using the kappa statistic. Plasma neurofilament light concentrations were measured for 55 participants as a marker of neurodegeneration and between group comparisons calculated. All diagnostic criteria showed good inter-rater reliability apart from mild neurocognitive disorder which was moderate (k=0.494). DSM- 5 criteria had substantial concurrence with clinical judgement (k=0.855). When compared to the no neurocognitive disorder group, average neurofilament light concentrations were higher in both the mild and major neurocognitive disorder groups. DSM-5 neurocognitive disorder criteria can be used reliably in a Down syndrome population and has higher concurrence with clinical judgement than the older DSM-IV and ICD-10 criteria. Whilst the inter-rater reliability of the mild neurocognitive disorder criteria was modest, it does appear to identify people in an early stage of dementia with underlying neurodegenerative changes, represented by higher average NfL levels.
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| 9. |
- Startin, C. M., et al.
(författare)
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Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer's disease
- 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
- BackgroundDown syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and controls will aid in understanding AD development in DS. We explored group differences in plasma concentrations of amyloid- peptides and tau (as their accumulation is a characteristic feature of AD) and cytokines (as the inflammatory response has been implicated in AD development, and immune dysfunction is common in DS).MethodsWe used ultrasensitive assays to compare plasma concentrations of the amyloid- peptides A(40) and A(42), total tau (t-tau), and the cytokines IL1, IL10, IL6, and TNF between adults with DS (n=31), adults with sAD (n=27), and controls age-matched to the group with DS (n=27), and explored relationships between molecular concentrations and with age within each group. In the group with DS, we also explored relationships with neurofilament light (NfL) concentration, due to its potential use as a biomarker for AD in DS.ResultsA(40), A(42), and IL1 concentrations were higher in DS, with a higher A(42)/A(40) ratio in controls. The group with DS showed moderate positive associations between concentrations of t-tau and both A(42) and IL1. Only NfL concentration in the group with DS showed a significant positive association with age.ConclusionsConcentrations of A(40) and A(42) were much higher in adults with DS than in other groups, reflecting APP gene triplication, while no difference in the A(42)/A(40) ratio between those with DS and sAD may indicate similar processing and deposition of A(40) and A(42) in these groups. Higher concentrations of IL1 in DS may reflect an increased vulnerability to infections and/or an increased prevalence of autoimmune disorders, while the positive association between IL1 and t-tau in DS may indicate IL1 is associated with neurodegeneration. Finally, NfL concentration may be the most suitable biomarker for dementia progression in DS. The identification of such a biomarker is important to improve the detection of dementia and monitor its progression, and for designing clinical intervention studies.
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| 10. |
- Adroja, D. T., et al.
(författare)
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Competing 4 f-electron dynamics in Ce(Ru1-xFex)(2)Al-10 (0
- 2013
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 87:22
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Tidskriftsartikel (refereegranskat)abstract
- We have carried out muon spin relaxation (mu SR), neutron diffraction, and inelastic neutron scattering (INS) investigations on polycrystalline samples of Ce(Ru1-xFex)(2)Al-10 (x = 0, 0.3, 0.5, 0.8, and 1) to investigate the nature of the ground state (magnetic ordered versus paramagnetic) and the origin of the spin-gap formation as evident from the bulk measurements in the end members. Our zero-field mu SR spectra clearly reveal coherent two-frequency oscillations at low temperature in x = 0, 0.3, and 0.5 samples, which confirm the long-range magnetic ordering of the Ce moment with Neel temperature T-N = 27, 26, and 21 K, respectively. On the other hand, the mu SR spectra of x = 0.8 and x = 1 down to 1.4 K and 0.045 K, respectively, exhibit a temperature-independent Kubo-Toyabe term, confirming a paramagnetic ground state. The long-range magnetic ordering in x = 0.5 below 21 K has been confirmed through the neutron diffraction study. INS measurements of x = 0 clearly reveal the presence of a sharp inelastic excitation near 8 meV between 5 K and 26 K, due to an opening of a gap in the spin excitation spectrum, which transforms into a broad response at and above 30 K. Interestingly, at 4.5 K, the spin-gap excitation broadens in x = 0.3 and exhibits two clear peaks at 8.4(3) and 12.0(5) meV in x = 0.5. In the x = 0.8 sample, which remains paramagnetic down to 1.2 K, there is a clear signature of a spin gap of 10-12 meV at 7 K, with a strong wave-vector-dependent intensity. Evidence of a spin gap of 12.5(5) meV has also been found in x = 1. The observation of a spin gap in the paramagnetic samples (x = 0.8 and 1) is an interesting finding in this study, and it challenges our understanding of the origin of the semiconducting gap in CeT2Al10 (T = Ru and Os) compounds in terms of a hybridization gap opening only a small part of the Fermi surface, gapped spin waves, or a spin-dimer gap.
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| 12. |
- Strydom, A., et al.
(författare)
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Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome
- 2018
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Down syndrome (DS) may be considered a genetic form of Alzheimer's disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions. Methods: We measured blood NF-L concentrations in 100 adults with DS using Simoa NF-light® assays, and we examined relationships with age as well as cross-sectional and longitudinal dementia diagnosis. Results: NF-L concentrations increased with age (Spearman's rho = 0.789, p < 0.001), with a steep increase after age 40, and they were predictive of dementia status (p = 0.022 adjusting for age, sex, and APOE4), but they showed no relationship with long-standing epilepsy or premorbid ability. Baseline NF-L concentrations were associated with longitudinal dementia status. Conclusions: NF-L is a biomarker for neurodegeneration in DS with potential for use in future clinical trials to prevent or delay dementia.
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| 13. |
- Costalago, David, et al.
(författare)
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Using stable isotope analysis to study the diet of Gilchristella aestuaria larvae : preliminary insights into the foodwebs of six South African estuaries
- 2016
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Ingår i: African Journal of Aquatic Science. - : National Inquiry Services Center (NISC). - 1608-5914 .- 1727-9364. ; 41:4, s. 389-398
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Tidskriftsartikel (refereegranskat)abstract
- South African estuarine systems are becoming increasingly altered by anthropogenic and environmental factors, but the consequences of such changes for these systems are still not fully understood. The most common approach for evaluating the ecological status of aquatic systems is studying their associated foodwebs. Due to their high abundance and important ecological role, the larvae of estuarine round herring Gilchristella aestuaria (Gilchrist, 1913) are key candidates for examining the foodweb structure and function of southern African estuaries. The foodwebs and trophic interactions of G. aestuaria larvae in six estuaries in South Africa were compared using larvae sampled in November 2013 and analysed using delta C-13 and delta N-15 and Bayesian isotopic mixing models. The main prey type for G. aestuaria larvae in all estuaries was zooplankton. We found a high similarity among the Kariega, Gamtoos, Great Fish and Sundays estuaries in terms of consumers and potential sources for both d13C and delta N-15 signatures. Significant differences were found in delta C-13 values among marine-dominated estuaries, such as the Kromme Estuary, and the more freshwater-dominated systems. In addition, in the Kromme Estuary particulate organic matter was very important in the diet of G. aestuaria larvae. Our results suggest that both food availability and physical environmental parameters strongly affect the diet and condition of G. aestuaria and, consequently, the entire foodweb in the system.
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| 14. |
- Lopez-Varela, Elisa, et al.
(författare)
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Drug concentration at the site of disease in children with pulmonary tuberculosis
- 2022
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 77:6, s. 1710-1719
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Tidskriftsartikel (refereegranskat)abstract
- Background Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. Objectives To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. Methods We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. Results Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. Conclusions Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.
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| 16. |
- Ashton, Nicholas J., et al.
(författare)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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| 17. |
- Costalago, David, et al.
(författare)
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Influence of environmental variables on the larval stages of anchovy, Engraulis encrasicolus, and sardine, Sardinops sagax, in Algoa Bay, South Africa
- 2018
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Ingår i: Environmental Biology of Fishes. - : Springer Science and Business Media LLC. - 0378-1909 .- 1573-5133. ; 101:2, s. 225-236
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the environmental drivers of larval abundance of anchovy Engraulis encrasicolus and sardine Sardinops sagax in Algoa Bay, Eastern Cape (South Africa). This study comprised a pre-drought post-drought time period, comparing the responses of the fish larvae to different factors before and after the drought. The current study presents, for the first time, which environmental variables are affecting the anchovy and sardine larvae populations in the region. Easterly wind speed and zooplankton density were the only environmental variables that presented a significant change between the pre- and post-drought periods, increasing after the drought. Generalized additive models (GAMs) were used in order to explore the effects that environmental factors might have in the abundance of anchovy and sardine larvae in Algoa Bay. Specifically, the GAM that best explained the deviance of the anchovy larvae dynamics included the covariates rainfall, easterly wind speed, Chl a concentration, sardine larvae abundance and the interactions SST*Chla and sard*SST. The GAM best explaining sardine larvae abundance included only the easterly wind speed as a covariate. This model showed that there was a positive relationship between the higher values of wind speed and sardine larvae abundance.
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| 18. |
- Montoliu-Gaya, Laia, et al.
(författare)
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Blood Biomarkers for Alzheimer's Disease in Down Syndrome
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:16
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer's disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-beta, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression-such as inflammatory dysregulation, energetic imbalance, or oxidative stress-have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future.
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