Evaluation of Adeno-Associated Viral Vectors for Liver-Directed Gene Transfer in Dogs

This study evaluated six adeno-associated viral (AAV) vectors expressing green fluorescent protein (GFP) from the liver-specific thyroid hormone–binding globulin (TBG) promoter made with novel capsids in canine liver-directed gene transfer. Studies in 1.5-month-old dogs, which were administered vector through a peripheral vein, showed that AAV8 capsid vectors had the most favorable performance profiles. Interestingly, the absolute levels of hepatocyte transduction achieved with AAV8 were lower in dogs compared with what had been achieved in mice and nonhuman primates. Additional studies were performed with AAV8 delivered into the hepatic artery in adult dogs, with higher doses of vector used to assess potential dose-limiting toxicities. These studies showed good transduction on day 7 in one dog that apparently was lost by day 28 in another dog through the generation of GFP-specific T cells. Each adult dog was carefully monitored for any hemodynamic changes associated with vector infusion. Both animals demonstrated mild to moderate hypotension and bradycardia, which appeared to be anesthesia-related, making it difficult to evaluate contributions of the vector

Antarctic sonobuoy surveys for blue whales from 2006-2021 reveal contemporary distribution, changes over time, and paths to further our understanding of their distribution and biology

Seven passive acoustic surveys for marine mammal sounds were conducted by deploying sonobuoys along ship tracks during Antarctic voyages spanning years 2006-2021. These surveys included nearly 330° of longitude throughout Antarctic (south of 60°S) and sub-Antarctic (between 50-60°S) latitudes. Here, we summarise the presence of calls from critically endangered Antarctic blue whales (Balaenoptera musculus intermedia) detected on all seven of these surveys. We describe and compare the spatial distribution of detections of three different types of Antarctic blue whale calls: unit-A, Z-calls, and D-calls. Three sets of voyages partially overlapped spatially but in different years, providing three regions (Indian Sector, Dumont d’Urville Sea, Ross Sea) to investigate differences over time for these three different call types. The proportion of sonobuoys with calls present was significantly higher in the more recent years for seven of the 15 combinations of years, regions, and call type. The proportion of sonobuoys with calls present was significantly lower only for one of the 15 combinations (unit A in the Ross Sea between 2015 vs 2017), and not significantly different for the remaining seven pairwise comparisons. We discuss possible explanations for these observations including: differences in probability of detection, whale behaviour, whale distribution, and abundance. These explanations are not mutually exclusive and cannot yet be resolved without application of complex analytical methods and collection of additional data. Lastly, we discuss future work that could help clarify the contributions of each of these potential drivers of acoustic detection. We propose continued acoustic data collection, application of new analytical methods, and collection of other synergistic data from Antarctic blue whales on their feeding grounds as a basis for future work on this species. This could provide a cost effective and holistic means of monitoring their status after the effects of 20th century industrial whaling, as well as their responses to natural and anthropogenic changes to their main prey, Antarctic krill, and a changing climate

No distinct local cuisines among humpback whales: A population diet comparison in the Southern Hemisphere

Southern hemisphere humpback whale (Megaptera novaeangliae, SHHW) breeding populations follow a high-fidelity Antarctic krill (Euphausia superba) diet while feeding in distinct sectors of the Southern Ocean. Their capital breeding life history requires predictable ecosystem productivity to fuel migration and migration-related behaviours. It is therefore postulated that populations feeding in areas subject to the strongest climate change impacts are more likely to show the first signs of a departure from a high-fidelity krill diet. We tested this hypothesis by investigating blubber fatty acid profiles and skin stable isotopes obtained from five SHHW populations in 2019, and comparing them to Antarctic krill stable isotopes sampled in three SHHW feeding areas in the Southern Ocean in 2019. Fatty acid profiles and δ13C and δ15N varied significantly among all five populations, however, calculated trophic positions did not (2.7 to 3.1). Similarly, fatty acid ratios, 16:1ω7c/16:0 and 20:5ω3/22:6ω3 were above 1, showing that whales from all five populations are secondary heterotrophs following an omnivorous diet with a diatom-origin. Thus, evidence for a potential departure from a high-fidelity Antarctic krill diet was not seen in any population. δ13C of all populations were similar to δ13C of krill sampled in productive upwelling areas or the marginal sea-ice zone. Consistency in trophic position and diet origin but significant fatty acid and stable isotope differences demonstrate that the observed variability arises at lower trophic levels. Our results indicate that, at present, there is no evidence of a divergence from a high-fidelity krill diet. Nevertheless, the characteristic isotopic signal of whales feeding in productive upwelling areas, or in the marginal sea-ice zone, implies that future cryosphere reductions could impact their feeding ecology

Surfacing rates, swim speeds, and patterns of movement of Antarctic blue whales

During three surveys in the austral summers of 2013, 2015, 2019, data on Antarctic blue whale blow rates, dive times, swim speeds, and broadscale movements were collected using video photogrammetric tracking and intra-voyage photo-identification. A total of 24.4 hours of video observations were suitable for blow interval or movement analysis. Similar to other blue whale populations, Antarctic blue whale dive behaviour comprised a sequence of short dives followed by a long dive with a mean dive time for short dives of 17.6 s, and a mean long dive time of 189.3 s. Two separate methods were used to estimate the average blow rate for Antarctic blue whales, giving estimates of 59.7 and 63.2 blows per hour. The overall mean swim speed over the course of all suitable video track segments was 1.59 ms-1, but there were significant differences between years in the mean of the overall movement rate for each track; average movement rates were lower in 2015 compared to 2013 and 2019 (0.90 ms-1, 1.84 and 1.55 ms-1 respectively), with higher rates of turning in 2015. In 2019, there was faster overall movement through the study area in a consistent direction. The total number of photo-identified blue whales re-sighted intra-season in 2013 was nine (out of 50 identified individuals); in 2015 it was seven (out of 46); in 2019 two (out of 25). Whales remained for several days with little overall movement within the 2015 study area, whereas they were moving through the study area in 2019, which would explain the low number of intra-season resights. The predominant heading in 2019 was towards the area of Antarctic blue whale concentrations at the entrance to the Ross Sea observed in previous years. The photo-identification data also show a high proportion of resighted whales with coherent movements. This suggests that Antarctic blue whales might travel together, at least over periods of several days or sometimes up to a month. The differences between behaviours in 2015 and 2019 in particular may be related to differences in the characteristics of krill swarms between the study areas

Ace Lake: three decades of research on a meromictic, Antarctic lake

Ace Lake (Vestfold Hills, Antarctica) has been investigated since the 1970s. Its close proximity to Davis Station has allowed year-long, as well as summer only, investigations. Ace Lake is a saline meromictic (permanently stratified) lake with strong physical and chemical gradients. The lake is one of the most studied lakes in continental Antarctica. Here we review the current knowledge of the history, the physical and chemical environment, community structure and functional dynamics of the mixolimnion, littoral benthic algal mats, the lower anoxic monimolimnion and the sediment within the monimolimnion. In common with other continental meromictic Antarctic lakes, Ace Lake possesses a truncated food web dominated by prokaryote and eukaryote microorganisms in the upper aerobic mixolimnion, and an anaerobic prokaryote community in the monimolimnion, where methanogenic Archaea, sulphate-reducing and sulphur-oxidizing bacteria occur. These communities are functional in winter at subzero temperatures, when mixotrophy plays an important role in survival in dominant photosynthetic eukaryotic microorganisms in the mixolimnion. The productivity of Ace Lake is comparable to other saline lakes in the Vestfold Hills, but higher than that seen in the more southerly McMurdo Dry Valley lakes. Finally we identify gaps in the current knowledge and avenues that demand further investigation, including comparisons with analogous lakes in the North Polar region

Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe

Annual plankton dynamics in an Antarctic saline lake

Summary 1. The plankton dynamics of Ace Lake, a saline, meromictic basin in the Vestfold Hills, eastern Antarctica was studied between December 1995 and February 1997. 2. The lake supported two distinct plankton communities; an aerobic microbial community in the upper oxygenated mixolimnion and an anaerobic microbial community in the lower anoxic monimolimnion. 3. Phytoplankton development was limited by nitrogen availability. Soluble reactive phosphorus was never limiting. Chlorophyll a concentrations in the mixolimnion ranged between 0.3 and 4.4 μg L−−1 during the study period and a deep chlorophyll maximum persisted throughout the year below the chemo/oxycline. 4. Bacterioplankton abundance showed considerable seasonal variation related to light and substrate availability. Autotrophic bacterial abundance ranged between 0.02 and 8.94 × 108 L−−1 and heterotrophic bacterial abundance between 1.26 and 72.8 × 108 L−−1 throughout the water column. 5. The mixolimnion phytoplankton was dominated by phytoflagellates, in particular Pyramimonas gelidicola. P. gelidicola remained active for most of the year by virtue of its mixotrophic behaviour. Photosynthetic dinoflagellates occurred during the austral summer, but the entire population encysted for the winter. 6. Two communities of heterotrophic flagellates were apparent; a community living in the upper monimolimnion and a community living in the aerobic mixolimnion. Both exhibited different seasonal dynamics. 7. The ciliate community was dominated by the autotroph Mesodinium rubrum. The abundance of M. rubrum peaked in summer. A proportion of the population encysted during winter. Only one other ciliate, Euplotes sp., occurred regularly. 8. Two species of Metazoa occurred in the mixolimnion; a calanoid copepod (Paralabidocera antarctica) and a rotifer (Notholca sp.). However, there was no evidence of grazing pressure on the microbial community. In common with most other Antarctic lakes, Ace Lake appears to be driven by ‘bottom-up’ forces

Protozoan growth rates in Antarctic lakes

The growth rates of heterotrophic nanoflagellates (HNAN), mixotrophic cryptophytes, dinoflagellates and ciliates in field assemblages from Ace Lake in the Vestfold Hills (eastern Antarctica) and Lakes Fryxell and Hoare (McMurdo Dry Valleys, western Antarctica), were determined during the austral summers of 1996/1997 and 1997/1998. The response of the nanoflagellates to temperature differed between lakes in eastern and western Antarctica. In Ace Lake the available bacterial food resources had little impact on growth rate, while temperature imposed an impact, whereas in Lake Hoare increased bacterial food resources elicited an increase in growth rate. However, the incorporation of published data from across Antarctica showed that temperature had the greater effect, but that growth is probably controlled by a suite of factors not solely related to bacterial food resources and temperature. Dinoflagellates had relatively high specific growth rates (0.0057–0.384 h−1), which were comparable to Antarctic lake ciliates and to dinoflagellates from warmer, lower latitude locations. Temperature did not appear to impose any significant impact on growth rates. Mixotrophic cryptophytes in Lake Hoare had lower specific growth rates than HNAN (0.0029–0.0059 h−1 and 0.0056–0.0127 h−1, respectively). They showed a marked seasonal variation in growth rate, which was probably related to photosynthetically active radiation under the ice at different depths in the water column. Ciliates' growth rates showed no relationship between food supply and mean cell volume, but did show a response to temperature. Specific growth rates ranged between 0.0033 and 0.150 h−1 for heterotrophic ciliates, 0.0143 h−1 for a mixotrophic Plagiocampa species and 0.0075 h−1 for the entirely autotrophic ciliate, Mesodinium rubrum. The data indicated that the scope for growth among planktonic Protozoa living in oligotrophic, cold extreme lake ecosystems is limited. These organisms are likely to suffer prolonged physiological stress, which may account for the highly variable growth rates seen within and between Antarctic lakes

Assessment of bacterial dependence on marine primary production along a northern latitudinal gradient

Recent observations in polar marine waters have shown that a large fraction of primary production may be lost to respiration by planktonic bacteria due to very low bacterial growth efficiencies in cold waters. Here we report that sea temperature may be a key factor influencing the interaction between bacteria and primary production in North Atlantic and Arctic waters, suggesting that low primary production rates could not sustain bacterial carbon demand in the coldest Arctic waters. The use of freshly produced phytoplankton exudate by bacteria in early- and mid-summer was assessed, together with the bacterial uptake of dissolved inorganic nitrogen (DIN = nitrate and ammonium), in surface waters along a latitudinal gradient from the North Sea to the Arctic sea ice. Bacterial production was independent of the low primary production measured in the coldest waters. Under these conditions, heterotrophic bacteria can consume a large fraction of DIN and N-rich organic matter, making them strong contributors to N fluxes in these waters