Alternative splicing of exon 10 in the tau gene as a target for treatment of tauopathies

Tau aggregation is one of the major features in Alzheimer's disease and in several other tauopathies, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and progressive supranuclear palsy (PSP). More than 35 mutations in the tau gene have been identified from FTDP-17 patients. A group of these mutations alters splicing of exon 10, resulting in an increase in exon 10 inclusion into tau mRNA. Abnormal splicing with inclusion of exon 10 into tau mRNA has also been observed in PSP and AD patients. These results indicate that abnormal splicing of exon 10, leading to the production of tau with exon 10, is probably one of the mechanisms by which tau accumulates and aggregates in tauopathic brains. Therefore, modulation of exon 10 splicing in the tau gene could potentially be targeted to prevent tauopathies. To identify small molecules or compounds that could potentially be developed into drugs to treat tauopathies, we established a cell-based high-throughput screening assay. In this review, we will discuss how realistic, specific biological molecules can be found to regulate exon 10 splicing in the tau gene for potential treatment of tauopathies

Local flexibility in feeding behaviour and contrasting microhabitat use of an omnivore across latitudes

As the environment is getting warmer and species are redistributed, consumers can be forced to adjust their interactions with available prey, and this could have cascading effects within food webs. To better understand the capacity for foraging flexibility, our study aimed to determine the diet variability of an ectotherm omnivore inhabiting kelp forests, the sea urchin Echinus esculentus, along its entire latitudinal distribution in the northeast Atlantic. Using a combination of gut content and stable isotope analyses, we determined the diet and trophic position of sea urchins at sites in Portugal (42° N), France (49° N), southern Norway (63° N), and northern Norway (70° N), and related these results to the local abundance and distribution of putative food items. With mean estimated trophic levels ranging from 2.4 to 4.6, omnivory and diet varied substantially within and between sites but not across latitudes. Diet composition generally reflected prey availability within epiphyte or understorey assemblages, with local affinities demonstrating that the sea urchin adjusts its foraging to match the small-scale distribution of food items. A net “preference” for epiphytic food sources was found in northern Norway, where understorey food was limited compared to other regions. We conclude that diet change may occur in response to food source redistribution at multiple spatial scales (microhabitats, sites, regions). Across these scales, the way that key consumers alter their foraging in response to food availability can have important implication for food web dynamics and ecosystem functions along current and future environmental gradients

Overwintering individuals of the Arctic krill Thysanoessa inermis appear tolerant to short-term exposure to low pH conditions

Areas of the Arctic Ocean are already experiencing seasonal variation in low pH/elevated pCO2 and are predicted to be the most affected by future ocean acidification (OA). Krill play a fundamental ecological role within Arctic ecosystems, serving as a vital link in the transfer of energy from phytoplankton to higher trophic levels. However, little is known of the chemical habitat occupied by Arctic invertebrate species, and of their responses to changes in seawater pH. Therefore, understanding krill’s responses to low pH conditions has important implications for the prediction of how Arctic marine communities may respond to future ocean change. Here, we present natural seawater carbonate chemistry conditions found in the late polar winter (April) in Kongsfjord, Svalbard (79°North) as well as the response of the Arctic krill, Thysanoessa inermis, exposed to a range of low pH conditions. Standard metabolic rate (measured as oxygen consumption) and energy metabolism markers (incl. adenosine triphosphate (ATP) and l-lactate) of T. inermis were examined. We show that after a 7 days experiment with T. inermis, no significant effects of low pH on MO2, ATP and l-lactate were observed. Additionally, we report carbonate chemistry from within Kongsfjord, which showed that the more stratified inner fjord had lower total alkalinity, higher dissolved inorganic carbon, pCO2 and lower pH than the well-mixed outer fjord. Consequently, our results suggest that overwintering individuals of T. inermis may possess sufficient ability to tolerate short-term low pH conditions due to their migratory behaviour, which exposes T. inermis to the naturally varying carbonate chemistry observed within Kongsfjord, potentially allowing T. inermis to tolerate future OA scenarios

Influence of iron, cobalt, and vitamin B12 supply on phytoplankton growth in the tropical East Pacific during the 2015 El Niño

Iron (Fe), cobalt (Co), and vitamin B12 addition experiments were performed in the eastern Equatorial Pacific/Peruvian upwelling zone during the 2015 El Niño event. Near the Peruvian coastline, apparent photosystem II photochemical efficiencies (Fv/Fm) were unchanged by nutrient addition and chlorophyll‐a tripled in untreated controls over two days, indicating nutrient replete conditions. Conversely, Fe amendment further away from the coastline in the high nitrate, low Fe zone significantly increased Fv/Fm and chlorophyll‐a concentrations. Mean chlorophyll‐a was further enhanced following supply of Fe+Co and Fe+B12 relative to Fe alone, but this was not statistically significant; further offshore, reported Co depletion relative to Fe could enhance responses. The persistence of Fe limitation in this system under a developing El Niño, as previously demonstrated under non‐El Niño conditions, suggests that diminished upwelled Fe is likely an important factor driving reductions in offshore phytoplankton productivity during these events