| 1. |
- Maresova, A., et al.
(author)
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Improved syntheses of P2X(7) ligands based on substituted benzyl amide of pyroglutamic acid motif labelled with iodine-123 or iodine-125
- 2023
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In: Journal of Radioanalytical and Nuclear Chemistry. - 0236-5731.
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Journal article (peer-reviewed)abstract
- P2X(7) sites are emerging targets for molecular imaging research, notably in the context of neurodegeneration and inflammatory conditions. Therefore, we prepared a precursor for (radio)iodination of the P2X(7) ligand VPGIS191. We then developed a radioiodination method with I-123 for SPECT with a radiochemical yield of 71 +/- 13% and I-125 for autoradiography with a radiochemical yield of 85 +/- 6% Autoradiography of [I-125]VPGIS191 in mouse brain cryostat sections demonstrated approximately 36 nM binding affinity and B-max of approximately 400 pmol/gram tissue for P2X(7) binding sites. VPGIS191 (cis) had a two-fold lower affinity compared to its geometric trans-isomer TZ6019.
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| 2. |
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| 3. |
- Biggs, Reinette, et al.
(author)
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Social-ecological change : insights from the Southern African Program on Ecosystem Change and Society
- 2022
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In: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 18:1, s. 447-468
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Journal article (peer-reviewed)abstract
- Social-ecological systems (SES) research has emerged as an important area of sustainability science, informing and supporting pressing issues of transformation towards more sustainable, just and equitable futures. To date, much SES research has been done in or from the Global North, where the challenges and contexts for supporting sustainability transformations are substantially different from the Global South. This paper synthesises emerging insights on SES dynamics that can inform actions and advance research to support sustainability transformations specifically in the southern African context. The paper draws on work linked to members of the Southern African Program on Ecosystem Change and Society (SAPECS), a leading SES research network in the region, synthesizing key insights with respect to the five core themes of SAPECS: (i) transdisciplinary and engaged research, (ii) ecosystem services and human well-being, (iii) governance institutions and management practices, (iv) spatial relationships and cross-scale connections, and (v) regime shifts, traps and transformations. For each theme, we focus on insights that are particularly novel, interesting or important in the southern African context, and reflect on key research gaps and emerging frontiers for SES research in the region going forward. Such place-based insights are important for understanding the variation in SES dynamics around the world, and are crucial for informing a context-sensitive global agenda to foster sustainability transformations at local to global scales.
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| 4. |
- Biggs, Reinette, et al.
(author)
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The Southern African Program on Ecosystem Change and Society : an emergent community of practice
- 2023
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In: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 19:1
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Journal article (peer-reviewed)abstract
- Sustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable, just and equitable futures. This paper synthesises insights from the development of a community of practice on social-ecological systems (SES) research in southern Africa over the past decade, linked to the international Programme on Ecosystem Change and Society (PECS). This community consists of a network of researchers who carry out place-based SES research in the southern African region. They interact through various cross-cutting working groups and also host a variety of public colloquia and student and practitioner training events. Known as the Southern African Program on Ecosystem Change and Society (SAPECS), its core objectives are to: (1) derive new approaches and empirical insights on SES dynamics in the southern African context; (2) have a tangible impact by mainstreaming knowledge into policy and practice; and (3) grow the community of practice engaged in SES research and governance, including researchers, students and practitioners. This paper reflects on experiences in building the SAPECS community, with the aim of supporting the development of similar networks elsewhere in the world, particularly in the Global South.
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| 5. |
- Huber, Maria, et al.
(author)
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Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
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In: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
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Journal article (peer-reviewed)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 6. |
- Meyer-Jacob, Carsten, 1984-, et al.
(author)
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Re-browning of Sudbury (Ontario, Canada) lakes now approaches pre-acid deposition lake-water dissolved organic carbon levels
- 2020
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 725
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Journal article (peer-reviewed)abstract
- Since the implementation of large-scale lake monitoring in the similar to 1980s, water color and dissolved organic carbon (DOC) concentrations have increased in many northern lakes (i.e., lake browning), impacting the functioning of aquatic ecosystems. In regions that formerly experienced high levels of acid deposition, this browning trend has been largely attributed to the recovery from the impacts of past acid deposition. However, the extent to which DOC levels have now returned to naturally higher, pre-industrial conditions is still poorly understood. In this study, we assessed whether DOC levels are still influenced by acid deposition in lakes near Sudbury, Ontario, a region that has been heavily affected by sulfur dioxide emissions from local metal smelting during the 20th century. We analyzed water chemistry monitoring data (1981-2018), together with comparisons between modern and pre-industrial DOC levels inferred from sediment spectroscopy, for 51 acid-sensitive and 24 buffered reference lakes across the Sudbury landscape. Since 1981, DOC concentrations doubled in acid-sensitive lakes, with a mean increase of +1.6 mg/L, whereas in more buffered reference lakes, mean DOC levels increased by only 0.8 mg/L. Similarly, sediment-inferred DOC trends indicate that current DOC levels are, on average, similar to 22% below pre-industrial levels in acid sensitive systems compared to only similar to 10% in buffered lakes. Weakening correlations between DOC and acidification-related water chemistry variables (e.g., pH, alkalinity, metals) further indicate a diminishing influence of acid deposition on DOC in Sudbury lakes. These results highlight the strong impact that acid deposition has historically had on lake-water DOC dynamics in this region, but also suggest that DOC levels are approaching natural baseline levels in less acid-sensitive lakes, and that other drivers, such as changes in climate or vegetation cover, are now becoming the dominant controls on changes in DOC concentrations.
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| 7. |
- Stockbauer, Anna, et al.
(author)
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Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
- 2024
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
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Journal article (peer-reviewed)abstract
- Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
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