Mapping pathogenic processes contributing to neurodegeneration in Drosophila models of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people and currently lacking available disease-modifying treatments. Appropriate disease models are necessary to investigate disease mechanisms and potential treatments. Drosophila melanogaster models of AD include the Aβ fly model and the AβPP-BACE1 fly model. In the Aβ fly model, the Aβ peptide is fused to a secretion sequence and directly overexpressed. In the AβPP-BACE1 model, human AβPP and human BACE1 are expressed in the fly, resulting in in vivo production of Aβ peptides and other AβPP cleavage products. Although these two models have been used for almost two decades, the underlying mechanisms resulting in neurodegeneration are not yet clearly understood. In this study, we have characterized toxic mechanisms in these two AD fly models. We detected neuronal cell death and increased protein carbonylation (indicative of oxidative stress) in both AD fly models. In the Aβ fly model, this correlates with high Aβ1-42 levels and down-regulation of the levels of mRNA encoding lysosomal-associated membrane protein 1, lamp1 (a lysosomal marker), while in the AβPP-BACE1 fly model, neuronal cell death correlates with low Aβ1-42 levels, up-regulation of lamp1 mRNA levels and increased levels of C-terminal fragments. In addition, a significant amount of AβPP/Aβ antibody (4G8)-positive species, located close to the endosomal marker rab5, was detected in the AβPP-BACE1 model. Taken together, this study highlights the similarities and differences in the toxic mechanisms which result in neuronal death in two different AD fly models. Such information is important to consider when utilizing these models to study AD pathogenesis or screening for potential treatments

Shipworm ecology in Swedish coastal waters

Shipworms (Teredinidae) are marine bivalves adopted for boring into submerged wood, which they efficiently fragmentize and consume. They thereby perform a vital ecosystem service, yet simultaneously they cause extensive damage to important man-made marine structures. In Swedish waters, which this thesis focuses on, shipworms are not only a threat against marine cultural buildings, ships, bridges, and harbour structures (all made of wood), but also against the invaluable historical wrecks in the Baltic Sea. Thus, it is crucial to have knowledge about their recruitment in this region. Shipworms, as many other marine species, have change its geographical distribution in numerous areas in concert with climate change. The first aim of my thesis was therefore to investigate the distribution and abundance of shipworms along the Swedish coast and to test the hypothesis that they had expanded their range into the Baltic Sea. Wooden test panels were submerged at 18 harbours along the coast, from Strömstad to Ystad, and around the Danish island of Bornholm. By comparing the results of this investigation to those from similar work in the 1970’s, it was clear that there was no evidence for range expansion of shipworms in the surface waters in this part of the Baltic Sea the last 35 years. The second aim was then to determine the probability of spread of shipworms further into the Baltic Sea in the near-future. A simple, GISbased, mechanistic climate envelope model was developed to predict the temporal and spatial distribution of environmental conditions that would permit reproduction and larval metamorphosis of the shipworm Teredo navalis. The model was parameterized with published tolerances for temperature, salinity and oxygen. In addition, a high-resolution three-dimensional hydrographic model was used to simulate the likelihood of spread of T. navalis larvae within the study area. The climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread to at present uninfested areas typically spread to areas unfavourable for their survival. Consequently, there is a low probability of natural spread of T. navalis further into the Baltic Sea in the near-future. The predicted prolongation of the breeding season was shown in the third study, where a substantial phenological shift in the time of recruitment of T. navalis over the last 35 years was observed. The period of intensive recruitment during the study period (2004 – 2006) was on average one month longer than that observed in the 1970´s. This extension was primarily at the end of the breeding season: intensive recruitment ended 26 days later in the 2000´s than in the 1970’s. These results correlated well with a highly significant increase of the sea surface temperature since the 1970´s. Strong positive relationships were also found between a mean sea surface temperature of 16 °C (the reported temperature at which T. navalis release larvae) and the day of the year on which intensive larval recruitment began, and ended. The prolongation of the breeding season observed here increases the likelihood of successful recruitment of shipworms at the range margins, and thereby increases the risk of damage to man-made structures in the future. Finally, factors influencing substrate detection and settlement (chemical cues and small-scale turbulence and flow) of shipworm larvae were investigated. Field experiments showed, for the first time, that natural populations of shipworm larvae are attracted to wooden substrates by waterborne chemical cues. Subsequent laboratory experiments indicated, however, that small-scale hydrodynamic patterns are probably more important in determining settlement success. In the field, significantly greater numbers of competent larvae were found adjacent to plankton net bags contained wooden panels than to empty control nets. Laboratory flume experiments using ecologically relevant flow conditions showed, however, that active swimming by larvae would only influence settlement probability within a few body lengths of the substrate to reach it by altering behaviour (swimming). Thus it seems probable that chemical cues are only important for settlement when currents have advected larvae close to wooden substrata

Data from: A phenological shift in the time of recruitment of the shipworm, Teredo navalis L., mirrors marine climate change

For many species, seasonal changes in key environmental variables such as food availability, light, and temperature drive the timing (“phenology”) of major life-history events. Extensive evidence from terrestrial, freshwater, and marine habitats shows that global warming is changing the timings of many biological events; however, few of these studies have investigated the effects of climate change on the phenology of larval recruitment in marine invertebrates. Here, we studied temperature-related phenological shifts in the breeding season of the shipworm Teredo navalis (Mollusca, Bivalvia). We compared data for the recruitment period of T. navalis along the Swedish west coast during 2004–2006 with similar data from 1971–1973, and related differences in recruitment timing to changes in sea surface temperature over the same period. We found no significant shift in the timing of onset of recruitment over this ~30-year time span, but the end of recruitment was an average of 26 days later in recent years, leading to significantly longer recruitment periods. These changes correlated strongly with increased sea surface temperatures and coincided with published thermal tolerances for reproduction in T. navalis. Our findings are broadly comparable with other reports of phenological shifts in marine species, and suggest that warmer sea surface temperatures are increasing the likelihood of successful subannual reproduction and intensifying recruitment of T. navalis in this region

Data for manuscript ECE-2015-11-00758.R1

Sea surface temperature (Celsius), and time of recruitment of the shipworm Teredo navalis (individuals/area) onto wooden test panels at the Swedish west coast 1971 - 1973 and 2004 - 2006

Climate envelope modeling and dispersal simulations show little risk of range extension of the Shipworm, Teredo navalis (L.), in the Baltic sea.

The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future

Natural Populations of Shipworm Larvae Are Attracted to Wood by Waterborne Chemical Cues

<div><p>The life cycle of many sessile marine invertebrates includes a dispersive planktonic larval stage whose ability to find a suitable habitat in which to settle and transform into benthic adults is crucial to maximize fitness. To facilitate this process, invertebrate larvae commonly respond to habitat-related chemical cues to guide the search for an appropriate environment. Furthermore, small-scale hydrodynamic conditions affect dispersal of chemical cues, as well as swimming behavior of invertebrate larvae and encounter with potential habitats. Shipworms within the family Teredinidae are dependent on terrestrially derived wood in order to complete their life cycle, but very little is known about the cues and processes that promote settlement. We investigated the potential for remote detection of settling substrate via waterborne chemical cues in teredinid larvae through a combination of empirical field and laboratory flume experiments. Natural populations of teredinid larvae were significantly more abundant close to wooden structures enclosed in plankton net compared to empty control nets, clearly showing that shipworm larvae can sense and respond to chemical cues associated with suitable settling substrate in the field. However, the flume experiments, using ecologically relevant flow velocities, showed that the boundary layer around experimental wooden panels was thin and that the mean flow velocity exceeded larval swimming velocity approximately 5 mm (≈ 25 larval body lengths) from the panel surface. Therefore, we conclude that the scope for remote detection of waterborne cues is limited and that the likely explanation for the higher abundance of shipworm larvae associated with the wooden panels in the field is a response to a cue during or after attachment on, or very near, the substrate. Waterborne cues probably guide the larva in its decision to remain attached and settle, or to detach and continue swimming and drifting until the next encounter with a solid substrate.</p></div

Field measurements.

<p>Proportional distribution of field flow velocities measured at 1 m depth outside the floating dock where wooden panels were deployed. Velocities were recorded every hour during 3 weeks using an acoustic doppler current profiler (ADCP).</p

Field experiment.

<p>Number of shipworm larvae collected around wooden panels wrapped in plankton net (Wood) or plankton net only (Controls) at two occasions (Tow 1 and 2). Letters above bars indicate significant differences between mean values based on the Student-Newman-Keuls multiple comparisons test (SNK, <i>P</i> < 0.05). Error bars show + SEM (n = 8).</p

Laboratory flume experiment.

<p>Flow velocity fields around wooden panels measured with particle image velocimetry (PIV). Green color represents masked out areas that could not be analyzed and these are somewhat larger than the wooden panel. Coloured areas represent flow velocities below 0.4 cm s^-1 i.e. twice the competent shipworm larva swimming speed. In white areas the flow velocity exceeds 0.4 cm s^-1.</p