Nunalleq, Stories from the Village of Our Ancestors:Co-designing a multivocal educational resource based on an archaeological excavation

This work was funded by the UK-based Arts and Humanities Research Council through grants (AH/K006029/1) and (AH/R014523/1), a University of Aberdeen IKEC Award with additional support for travel and subsistence from the University of Dundee, DJCAD Research Committee RS2 project funding. Thank you to the many people who contributed their support, knowledge, feedback, voices and faces throughout the project, this list includes members of the local community, colleagues, specialists, students, and volunteers. If we have missed out any names we apologize but know that your help was appreciated. Jimmy Anaver, John Anderson, Alice Bailey, Kieran Baxter, Pauline Beebe, Ellinor Berggren, Dawn Biddison, Joshua Branstetter, Brendan Body, Lise Bos, Michael Broderick, Sarah Brown, Crystal Carter, Joseph Carter, Lucy Carter, Sally Carter, Ben Charles, Mary Church, Willard Church, Daniele Clementi, Annie Cleveland, Emily Cleveland, Joshua Cleveland, Aron Crowell, Neil Curtis, Angie Demma, Annie Don, Julia Farley, Veronique Forbes, Patti Fredericks, Tricia Gillam, Sean Gleason, Sven Haakanson, Cheryl Heitman, Grace Hill, Diana Hunter, Joel Isaak, Warren Jones, Stephan Jones, Ana Jorge, Solveig Junglas, Melia Knecht, Rick Knecht, Erika Larsen, Paul Ledger, Jonathan Lim Soon, Amber Lincoln, Steve Luke, Francis Lukezic, Eva Malvich, Pauline Matthews, Roy Mark, Edouard Masson-MacLean, Julie Masson-MacLean, Mhairi Maxwell, Chuna Mcintyre, Drew Michael, Amanda Mina, Anna Mossolova, Carl Nicolai Jr, Chris Niskanen, Molly Odell, Tom Paxton, Lauren Phillips, Lucy Qin, Charlie Roberts, Chris Rowe, Rufus Rowe,Chris Rowland, John Rundall, Melissa Shaginoff, Monica Shah, Anna Sloan, Darryl Small Jr, John Smith, Mike Smith, Joey Sparaga, Hannah Strehlau, Dora Strunk, Larissa Strunk, Lonny Strunk, Larry Strunk, Robbie Strunk, Sandra Toloczko, Richard Vanderhoek, the Qanirtuuq Incorporated Board, the Quinhagak Dance Group and the staff at Kuinerrarmiut Elitnaurviat. We also extend our thanks to three anonymous reviewers for their valuable comments on our paper.Peer reviewedPublisher PD

New Antarctic gravity anomaly grid for enhanced geodetic and geophysical studies in Antarctica

Gravity surveying is challenging in Antarctica because of its hostile environment and inaccessibility. Nevertheless, many ground-based, airborne, and shipborne gravity campaigns have been completed by the geophysical and geodetic communities since the 1980s. We present the first modern Antarctic-wide gravity data compilation derived from 13 million data points covering an area of 10 million km2, which corresponds to 73% coverage of the continent. The remove-compute-restore technique was applied for gridding, which facilitated leveling of the different gravity data sets with respect to an Earth gravity model derived from satellite data alone. The resulting free-air and Bouguer gravity anomaly grids of 10 km resolution are publicly available. These grids will enable new high-resolution combined Earth gravity models to be derived and represent a major step forward toward solving the geodetic polar data gap problem. They provide a new tool to investigate continental-scale lithospheric structure and geological evolution of Antarctica

Exploring the Dynamic Range of the Kinetic Exclusion Assay in Characterizing Antigen-Antibody Interactions

Therapeutic antibodies are often engineered or selected to have high on-target binding affinities that can be challenging to determine precisely by most biophysical methods. Here, we explore the dynamic range of the kinetic exclusion assay (KinExA) by exploiting the interactions of an anti-DKK antibody with a panel of DKK antigens as a model system. By tailoring the KinExA to each studied antigen, we obtained apparent equilibrium dissociation constants (KD values) spanning six orders of magnitude, from approximately 100 fM to 100 nM. Using a previously calibrated antibody concentration and working in a suitable concentration range, we show that a single experiment can yield accurate and precise values for both the apparent KD and the apparent active concentration of the antigen, thereby increasing the information content of an assay and decreasing sample consumption. Orthogonal measurements obtained on Biacore and Octet label-free biosensor platforms further validated our KinExA-derived affinity and active concentration determinations. We obtained excellent agreement in the apparent affinities obtained across platforms and within the KinExA method irrespective of the assay orientation employed or the purity of the recombinant or native antigens

Wnt signalling in human breast cancer: expression of the putative Wnt inhibitor Dickkopf-3 (DKK3) is frequently suppressed by promoter hypermethylation in mammary tumours

INTRODUCTION: Expression of the putative Wnt signalling inhibitor Dickkopf-3 (DKK3) is frequently lost in human cancer tissues because of aberrant 5'-cytosine methylation within the DKK3 gene promoter. Since other Wnt signalling inhibitors have been reported to be targets of epigenetic inactivation in human breast cancer, we questioned if DKK3 expression is also epigenetically silenced during breast carcinogenesis and therefore might contribute to oncogenic Wnt signalling commonly found in this disease. METHODS: DKK3 mRNA expression and DKK3 promoter methylation were determined by RT-PCR, realtime PCR and methylation-specific PCR in breast cell lines (n = 9), normal breast tissues (n = 19) and primary breast carcinomas (n = 150), respectively. In vitro DNA demethylation was performed by incubating breast cell lines with 5-aza-2'-deoxycytidine and trichostatin A. DKK3 protein expression was analysed by immunohistochemistry in breast carcinomas (n = 16) and normal breast tissues (n = 8). Methylation data were statistically correlated with clinical patient characteristics. All statistical evaluations were performed with SPSS 14.0 software. RESULTS: DKK3 mRNA was downregulated in 71% (five of seven) of breast cancer cell lines and in 68% of primary breast carcinomas (27 of 40) compared with benign cell lines and normal breast tissues, respectively. A DNA demethylating treatment of breast cell lines resulted in strong induction of DKK3 mRNA expression. In tumourous breast tissues, DKK3 mRNA downregulation was significantly associated with DKK3 promoter methylation (p < 0.001). Of the breast carcinomas, 61% (92 of 150) revealed a methylated DKK3 promoter, whereas 39% (58 of 150) retained an unmethylated promoter. Loss of DKK3 expression in association with DKK3 promoter methylation (p = 0.001) was also confirmed at the protein level (p < 0.001). In bivariate analysis, DKK3 promoter methylation was not associated with investigated clinicopathological parameters except patient age (p = 0.007). CONCLUSIONS: DKK3 mRNA expression and consequently DKK3 protein expression become frequently downregulated during human breast cancer development due to aberrant methylation of the DKK3 promoter. Since DKK3 is thought to negatively regulate oncogenic Wnt signalling, DKK3 may be a potential tumour suppressor gene in normal breast tissue

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size