| 1. |
- Alafuzoff, Irina, et al.
(författare)
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Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions : an inter-laboratory study by the BrainNet Europe consortium
- 2015
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 122:7, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.
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| 2. |
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| 3. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018-2019 European droughts : a collective need for unifying drought risk management
- 2022
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981. ; 22:6, s. 2201-2217
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Tidskriftsartikel (refereegranskat)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets.
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| 4. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018–2019 European droughts: A collective need for unifying drought risk management
- 2021
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazardous severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts, and how the hazard is perceived by relevant stakeholders for inducing action. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard and impacts. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders’ perceptions of drought, impacts on water resources and beyond, water availability and current drought management strategies at national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perceptions across different countries and in values of implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study concludes with an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and lessen harm to human and natural potentials.
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| 5. |
- Collani, Silvio, et al.
(författare)
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FT Modulates Genome-Wide DNA-Binding of the bZIP Transcription Factor FD
- 2019
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Ingår i: Plant Physiology. - : American Society of Plant Biologists. - 0032-0889 .- 1532-2548. ; 180:1, s. 367-380
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Tidskriftsartikel (refereegranskat)abstract
- The transition to flowering is a crucial step in the plant life cycle that is controlled by multiple endogenous and environmental cues, including hormones, sugars, temperature, and photoperiod. Permissive photoperiod induces the expression of FLOWERING LOCUS T (FT) in the phloem companion cells of leaves. The FT protein then acts as a florigen that is transported to the shoot apical meristem, where it physically interacts with the Basic Leucine Zipper Domain transcription factor FD and 14-3-3 proteins. However, despite the importance of FD in promoting flowering, its direct transcriptional targets are largely unknown. Here, we combined chromatin immunoprecipitation sequencing and RNA sequencing to identify targets of FD at the genome scale and assessed the contribution of FT to DNA binding. We further investigated the ability of FD to form protein complexes with FT and TERMINAL FLOWER1 through interaction with 14-3-3 proteins. Importantly, we observed direct binding of FD to targets involved in several aspects of plant development. These target genes were previously unknown to be directly related to the regulation of flowering time. Our results confirm FD as a central regulator of floral transition at the shoot meristem and provide evidence for crosstalk between the regulation of flowering and other signaling pathways, such as pathways involved in hormone signaling.
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| 6. |
- Fritschi, Sarah K., et al.
(författare)
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A beta seeds resist inactivation by formaldehyde
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Verlag (Germany). - 0001-6322 .- 1432-0533. ; 128:4, s. 477-484
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral beta-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated beta-amyloid (A beta) into young, pre-depositing A beta precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated A beta itself. Here we report that the beta-amyloid-inducing activity of Alzheimers disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated A beta are maintained in fixed tissues. The resistance of A beta seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of A beta aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.
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| 7. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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| 8. |
- Lee, Joanne E., et al.
(författare)
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A gibberellin methyltransferase modulates the timing of floral transition at the Arabidopsis shoot meristem
- 2020
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Ingår i: Physiologia Plantarum. - : John Wiley & Sons. - 0031-9317 .- 1399-3054. ; 170:4, s. 474-487
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Tidskriftsartikel (refereegranskat)abstract
- The transition from vegetative to reproductive growth is a key event in the plant life cycle. Plants therefore use a variety of environmental and endogenous signals to determine the optimal time for flowering to ensure reproductive success. These signals are integrated at the shoot apical meristem (SAM), which subsequently undergoes a shift in identity and begins producing flowers rather than leaves, while still maintaining pluripotency and meristematic function. Gibberellic acid (GA), an important hormone associated with cell growth and differentiation, has been shown to promote flowering in many plant species including Arabidopsis thaliana , but the details of how spatial and temporal regulation of GAs in the SAM contribute to floral transition are poorly understood. In this study, we show that the gene GIBBERELLIC ACID METHYLTRANSFERASE 2 (GAMT2 ), which encodes a GA‐inactivating enzyme, is significantly upregulated at the SAM during floral transition and contributes to the regulation of flowering time. Loss of GAMT2 function leads to early flowering, whereas transgenic misexpression of GAMT2 in specific regions around the SAM delays flowering. We also found that GAMT2 expression is independent of the key floral regulator LEAFY but is strongly increased by the application of exogenous GA. Our results indicate that GAMT2 is a repressor of flowering that may act as a buffer of GA levels at the SAM to help prevent premature flowering.
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| 9. |
- Lee, Joanne E., et al.
(författare)
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CRISPR-based tools for targeted transcriptional and epigenetic regulation in plants
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Programmable gene regulators that can modulate the activity of selected targets in trans are a useful tool for probing and manipulating gene function. CRISPR technology provides a convenient method for gene targeting that can also be adapted for multiplexing and other modifications to enable strong regulation by a range of different effectors. We generated a vector toolbox for CRISPR/dCas9-based targeted gene regulation in plants, modified with the previously described MS2 system to amplify the strength of regulation, and using Golden Gate-based cloning to enable rapid vector assembly with a high degree of flexibility in the choice of promoters, effectors and targets. We tested the system using the floral regulator FLOWERING LOCUS T (FT) as a target and a range of different effector domains including the transcriptional activator VP64, the H3K27 acetyltransferase p300 and the H3K9 methyltransferase KRYPTONITE. When transformed into Arabidopsis thaliana, several of the constructs caused altered flowering time phenotypes that were associated with changes in FT expression and/or epigenetic status, thus demonstrating the effectiveness of the system. The MS2-CRISPR/dCas9 system can be used to modulate transcriptional activity and epigenetic status of specific target genes in plants, and provides a versatile tool that can easily be used with different targets and types of regulation for a range of applications.
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| 10. |
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