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- Falahzadeh, A., et al.
(author)
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A New Coastal Crawler Prototype to Expand the Ecological Monitoring Radius of OBSEA Cabled Observatory
- 2023
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In: Journal of Marine Science and Engineering. ; 11:4
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Journal article (peer-reviewed)abstract
- The use of marine cabled video observatories with multiparametric environmental data collection capability is becoming relevant for ecological monitoring strategies. Their ecosystem surveying can be enforced in real time, remotely, and continuously, over consecutive days, seasons, and even years. Unfortunately, as most observatories perform such monitoring with fixed cameras, the ecological value of their data is limited to a narrow field of view, possibly not representative of the local habitat heterogeneity. Docked mobile robotic platforms could be used to extend data collection to larger, and hence more ecologically representative areas. Among the various state-of-the-art underwater robotic platforms available, benthic crawlers are excellent candidates to perform ecological monitoring tasks in combination with cabled observatories. Although they are normally used in the deep sea, their high positioning stability, low acoustic signature, and low energetic consumption, especially during stationary phases, make them suitable for coastal operations. In this paper, we present the integration of a benthic crawler into a coastal cabled observatory (OBSEA) to extend its monitoring radius and collect more ecologically representative data. The extension of the monitoring radius was obtained by remotely operating the crawler to enforce back-and-forth drives along specific transects while recording videos with the onboard cameras. The ecological relevance of the monitoring-radius extension was demonstrated by performing a visual census of the species observed with the crawler's cameras in comparison to the observatory's fixed cameras, revealing non-negligible differences. Additionally, the videos recorded from the crawler's cameras during the transects were used to demonstrate an automated photo-mosaic of the seabed for the first time on this class of vehicles. In the present work, the crawler travelled in an area of 40 m away from the OBSEA, producing an extension of the monitoring field of view (FOV), and covering an area approximately 230 times larger than OBSEA's camera. The analysis of the videos obtained from the crawler's and the observatory's cameras revealed differences in the species observed. Future implementation scenarios are also discussed in relation to mission autonomy to perform imaging across spatial heterogeneity gradients around the OBSEA.
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- Hornemann, S, et al.
(author)
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Mechanistic and structural aspects of the interaction of luminescent conjugated polymers with amyloid oligomers
- 2010
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In: Amyloid. - : Informa Healthcare. - 1350-6129 .- 1744-2818. ; 17:S1, s. 98-99
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Journal article (other academic/artistic)abstract
- Protein misfolding and aggregation diseases, such as e.g. Alzheimer’s disease, are associated by the accumulation of a disease-related protein. The pathogenic mechanisms involved in these confor- mational diseases are only poorly understood. Luminescent-conjugated polymers (LCPs) have been shown as a sensitive tool for detection of amyloid deposits. In contrast to commonly used amyloidotropic dyes such as thioflavins or Congo Red, LCPs are composed of flexible polythiophene chains which allow rotation of the molecule. Upon binding to amyloids, the LCPs alter their spectral properties in a conformation dependent manner. However, there is still limited information available on the binding mechanism and binding properties of the LCPs to amyloid fibrils and oligomers.We have produced recombinant human Aβ1-42 (recAβ1-42) protein in Escherichia coli and purified it by conventional chromatographic techniques in large quantities. The recAβ-protein was incubated in the presence of SDS to induce formation of homogenous, globular Aβ-oligomers with a size of approximately 60 kDa, known as Aβ-globulomers. We present first biophysical and spectroscopic data used to study the binding and structural properties of the complex formed by the globulomers and LCPs with various charged side chains. These data will provide a more detailed knowledge of the binding mode of amyloidogenic probes which is essential for understanding the structural char- acteristics of amyloid fibrils detected by thesemolecules.
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- Losa, Marco, et al.
(author)
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The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis
- 2024
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In: EMBO Molecular Medicine. - : SPRINGERNATURE. - 1757-4676 .- 1757-4684.
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Journal article (peer-reviewed)abstract
- Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed A beta amyloid in Alzheimer's disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Recombinant ASC specks accelerated SAA fibril formation and mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain (PYD). In a murine model of inflammatory AA amyloidosis, splenic amyloid load was conspicuously decreased in Pycard-/- mice which lack ASC. Treatment with anti-ASC(PYD) antibodies decreased amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (-logEC(50 )>= 2) in 19,334 hospital patients was <0.01%, suggesting that anti-ASC antibody treatment modalities would not be confounded by natural autoimmunity. These findings expand the role played by ASC and IL-1 independent inflammasome employments to extraneural proteinopathies and suggest that anti-ASC immunotherapy may contribute to resolving such diseases.
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- Meisl, Georg, et al.
(author)
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Scaling behaviour and rate-determining steps in filamentous self-assembly
- 2017
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 8:10, s. 7087-7097
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Journal article (peer-reviewed)abstract
- The formation of filaments from naturally occurring protein molecules is a process at the core of a range of functional and aberrant biological phenomena, such as the assembly of the cytoskeleton or the appearance of aggregates in Alzheimer's disease. The macroscopic behaviour associated with such processes is remarkably diverse, ranging from simple nucleated growth to highly cooperative processes with a well-defined lagtime. Thus, conventionally, different molecular mechanisms have been used to explain the self-assembly of different proteins. Here we show that this range of behaviour can be quantitatively captured by a single unifying Petri net that describes filamentous growth in terms of aggregate number and aggregate mass concentrations. By considering general features associated with a particular network connectivity, we are able to establish directly the rate-determining steps of the overall aggregation reaction from the system's scaling behaviour. We illustrate the power of this framework on a range of different experimental and simulated aggregating systems. The approach is general and will be applicable to any future extensions of the reaction network of filamentous self-assembly.
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- Ries, Jonas, et al.
(author)
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Superresolution Imaging of Amyloid Fibrils with Binding-Activated Probes
- 2013
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In: ACS Chemical Neuroscience. - : American Chemical Society. - 1948-7193. ; 4:7, s. 1057-1061
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Journal article (peer-reviewed)abstract
- Protein misfolding into amyloid-like aggregates underlies many neurodegenerative diseases. Thus, insights into the structure and function of these amyloids will provide valuable information on the pathological mechanisms involved and aid in the design of improved drugs for treating amyloid-based disorders. However, determining the structure of endogenous amyloids at high resolution has been difficult. Here we employ binding-activated localization microscopy (BALM) to acquire superresolution images of alpha-synuclein amyloid fibrils with unprecedented optical resolution. We propose that BALM imaging can be extended to study the structure of other amyloids, for differential diagnosis of amyloid-related diseases and for discovery of drugs that perturb amyloid structure for therapy.
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- Schuetz, Anne K., et al.
(author)
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Binding of Polythiophenes to Amyloids : Structural Mapping of the Pharmacophore
- 2018
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In: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:3, s. 475-481
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Journal article (peer-reviewed)abstract
- Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. 560 We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene.
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- Sigurdson, C.J., et al.
(author)
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Prion strain discrimination using luminescent conjugated polymers
- 2007
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 4:12, s. 1023-1030
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Journal article (peer-reviewed)abstract
- The occurrence of multiple strains of prions may reflect conformational variability of PrPSc, a disease-associated, aggregated variant of the cellular prion protein, PrPC. Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes.
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20. |
- Weaver, P. P.E., et al.
(author)
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Assessing plume impacts caused by polymetallic nodule mining vehicles
- 2022
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In: Marine Policy. - 0308-597X. ; 139
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Journal article (peer-reviewed)abstract
- Deep-sea mining may be just a few years away and yet society is struggling to assess the positive aspects, such as increasing the supply of metals for battery production to fuel the green revolution, versus the potentially large environmental impacts. Mining of polymetallic (manganese) nodules from the deep ocean is likely to be the first mineral resource targeted and will involve direct impacts to hundreds of km2 of seabed per mine per year. However, the mining activity will also cause the generation of large sediment plumes that will spread away from the mine site and have both immediate and long-term effects over much wider areas. We discuss what the impacts of plumes generated near the seabed by mining vehicles may be and how they might be measured in such challenging environments. Several different mining vehicles are under development around the world and depending on their design some may create larger plumes than others. We discuss how these vehicles could be compared so that better engineering designs could be selected and to encourage innovation in dealing with plume generation and spread. These considerations will aid the International Seabed Authority (ISA) that has the task of regulating mining activities in much of the deep sea in its commitment to promote the Best Available Technology (BAT) and Best Environmental Practice (BEP).
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