Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). In cell-free assays, Httex1p also inhibits the acetyltransferase activity of at least three enzymes: p300, P/CAF and CBP. Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC). In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease. These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms.
Various species of algae can produce marine toxins under certain circumstances. These toxins can then accumulate in shellfish such as mussels, oysters and scallops. When these contaminated shellfish species are consumed severe intoxication can occur. The different types of syndromes that can occur after consumption of contaminated shellfish, the corresponding toxins and relevant legislation are discussed in this review. Amnesic Shellfish Poisoning (ASP), Paralytic Shellfish Poisoning (PSP), Diarrheic Shellfish Poisoning (DSP) and Azaspiracid Shellfish Poisoning (AZP) occur worldwide, Neurologic Shellfish Poisoning (NSP) is mainly limited to the USA and New Zealand while the toxins causing DSP and AZP occur most frequently in Europe. The latter two toxin groups are fat-soluble and can therefore also be classified as lipophilic marine toxins. A detailed overview of the official analytical methods used in the EU (mouse or rat bioassay) and the recently developed alternative methods for the lipophilic marine toxins is given. These alternative methods are based on functional assays, biochemical assays and chemical methods. From the literature it is clear that chemical methods offer the best potential to replace the animal tests that are still legislated worldwide. Finally, an overview is given of the situation of marine toxins in The Netherlands. The rat bioassay has been used for monitoring DSP and AZP toxins in The Netherlands since the 1970s. Nowadays, a combination of a chemical method and the rat bioassay is often used. In The Netherlands toxic events are mainly caused by DSP toxins, which have been found in Dutch shellfish for the first time in 1961, and have reoccurred at irregular intervals and in varying concentrations. From this review it is clear that considerable effort is being undertaken by various research groups to phase out the animal tests that are still used for the official routine monitoring programs.
The “Dutch Energy Agreement” motivates governments and industries to invest in renewable energy sources, of which offshore wind energy is one of the solutions to meet the agreed target of 16% of the total energy budget from renewable resources by 2023. An option for the multi-use of wind farms is nature-inclusive building, in which the design and construction of wind farms make use of the potential for co-design with oyster bed restoration. This can support the government’s ambitions, for the Dutch North Sea, to achieve biodiversity goals, restore ecosystem functions, and enhance ecosystem services, including future seafood production. For the recovery of flat oyster (Ostrea edulis) beds, knowledge is required about the conditions under which active restoration of this species in the North Sea can be successfully implemented. This paper gives a framework and presents results to determine suitability of wind farms for flat oyster restoration, and provides recommendations for pilot studies. Our analysis showed that a number of wind farms in the Dutch section of the North Sea are suitable locations for development of flat oyster beds. Combining oyster restoration and oyster culture, as a protein source, is a viable option worth investigating.
Tetrodotoxin (TTX) is traditionally associated with seafood from tropical regions, but recently TTX was detected in bivalve mollusks in more temperate European waters. In The Netherlands it was therefore decided to monitor TTX in shellfish harvested from Dutch production areas. All shellfish production areas were monitored in 2015, 2016 and 2017. Samples were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In total 1063 samples were investigated, and the highest concentrations were observed in 2016, i.e., 253 µg TTX/kg in oysters and 101 µg TTX/kg in mussels. No TTX analogues, with the exception of 4-epi-TTX in one single sample, were found and contaminated samples also showed positive results in the neuro-2a bioassay. The occurrence of TTX seems to be consistent over the last three years with the highest concentrations observed annually in late June. The causative organism and the reasons why specific Dutch production areas are affected while others are not, are still unclear. Initially in The Netherlands an action limit of 20 µg TTX/kg was used to ensure the safety of consumers (2016), but recently The European Food Safety Authority (EFSA) established an acute reference dose, and based on a high portion size of consuming 400 g mussels, this dose was translated into a safe concentration of 44 µg TTX per kg for shellfish. This concentration is now used as an action limit and TTX is formally included in the Dutch shellfish monitoring program.
Seaweeds are increasingly seen as an alternative to land-grown products in food and feed applications. Interest in production of seaweeds in temperate waters is rising, in particular in combination with offshore wind energy generation. This article reports an investigation of the economic feasibility of seaweed production in the North Sea using economic modelling. Often, an overly positive picture of the costs and benefits of seaweed production is sketched. Based on current available information, offshore seaweed production in the North Sea is not economically feasible. Sensitivity analysis shows that revenues would have to increase by roughly 300%, all other things equal, to make a profit. A number of opportunities to improve the economic feasibility of a North Sea seaweed value chain are identified. Technical innovation and the design of systems that enable multiple harvests per year can reduce production costs. Successful marketing of seaweed as human food, and the development of biorefinery concepts can increase the value of the produced seaweed.
Following the Blue Growth ambition of the European Commission, the interest in the potential of offshore is growing. This paper aimed to contribute to the discussion on the feasibility of offshore aquaculture development and its potential for multi-use with other maritime activities. A review of national and international projects forms the basis of the paper, where the Dutch North Sea is used as a case-study area. Analysis of technical, economic and ecological boundaries indicated that the potential of fish culture is limited, that seaweed cultivation is likely to gain potential when challenges related to processing will be overcome and that mussel culture has the highest potential in the near future. The North Sea is an area where many stakeholders claim space, which might set boundaries to the number of sites available for mussel culture. Competing claims are a potential source of conflict but may also lead to mutual benefits when smart combinations are sought, e.g. with wind parks, fisheries and nature conservation; especially, the possibility of combining mussel culture in or around wind parks is worthwhile to be further explored. A spatial distribution model adapted for the Dutch North Sea conditions demonstrated that offshore mussel production in wind farms can be profitable. Yet, the commercial interest for offshore development of mussel culture is still limited. Actions required to stimulate further development of the offshore mussel industry are presented for the government, the private sector, research institutes and civil society organizations.
In fish farming, economic values (EV) of breeding goal traits are lacking, even though they are key parameters when defining selection objectives. The aim of this study was to develop a bioeconomic model to estimate EV of 2 traits representing production performances in fish farming: the thermal growth coefficient (TGC) and the feed conversion ratio (FCR). This approach was applied to a farm producing African catfish (Clarias gariepinus) in a recirculating aquaculture system (RAS). In the RAS, 2 factors could limit production level: the nitrogen treatment capacity of the biofilter or the fish density in rearing tanks at harvest. Profit calculation includes revenue from fish sales, cost of juveniles, cost of feed, cost of waste water treatment, and fixed costs. In the reference scenario, profit was modeled to zero. EV were calculated as the difference in profit per kilogram of fish between the current population mean for both traits (µt) and the next generation of selective breeding (µt+Δt) for either TGC or FCR. EV of TGC and FCR were calculated for three generations of hypothetical selection on either TGC or FCR (respectively 6.8% and 7.6% improvement per generation). The results show that changes in TGC and FCR can affect both the number of fish that can be stocked (number of batches per year and number of fish per batch) and the factor limiting production. The EV of TGC and FCR vary and depend on the limiting factors. When dissolved NH3-N is the limiting factor for both µt and µt+Δt, increasing TGC decreases the number of fish that can be stocked but increases the number of batches that can be grown. As a result, profit remains constant and EVTGC is zero. Increasing FCR, however, increases the number of fish stocked and the ratio of fish produced per kilogram of feed consumed ("economic efficiency"). The EVFCR is 0.14 €/kg of fish, and profit per kilogram of fish increases by about 10%. When density is the limiting factor for both µt and µt+Δt, the number of fish stocked per batch is fixed; therefore, extra profit is obtained by increasing either TGC, which increases the annual number of batches, or by decreasing FCR, which decreases annual feed consumption. EVTGC is 0.03 €/kg of fish and EVFCR is 0.05-0.06 €/kg of fish. These results emphasize the importance of calculating economic values in the right context to develop efficient future breeding programs in aquaculture.
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