76 results on '"Max Friesen"'
Search Results
2. SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
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Alexsia Richards, Max Friesen, Andrew Khalil, M. Inmaculada Barrasa, Lee Gehrke, and Rudolf Jaenisch
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Health sciences ,immunology ,virology ,stem cells research ,transcriptomics ,Science - Abstract
Summary: Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.
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- 2022
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3. LINE1-Mediated Reverse Transcription and Genomic Integration of SARS-CoV-2 mRNA Detected in Virus-Infected but Not in Viral mRNA-Transfected Cells
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Liguo Zhang, Punam Bisht, Anthony Flamier, M. Inmaculada Barrasa, Max Friesen, Alexsia Richards, Stephen H. Hughes, and Rudolf Jaenisch
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SARS-CoV-2 ,LINE1 ,retrotransposition ,WGS ,enrichment sequencing ,RNA transfection ,Microbiology ,QR1-502 - Abstract
SARS-CoV-2 sequences can be reverse-transcribed and integrated into the genomes of virus-infected cells by a LINE1-mediated retrotransposition mechanism. Whole-genome sequencing (WGS) methods detected retrotransposed SARS-CoV-2 subgenomic sequences in virus-infected cells overexpressing LINE1, while an enrichment method (TagMap) identified retrotranspositions in cells that did not overexpress LINE1. LINE1 overexpression increased retrotranspositions about 1000-fold as compared to non-overexpressing cells. Nanopore WGS can directly recover retrotransposed viral and flanking host sequences, but its sensitivity depends on the depth of sequencing (a typical 20-fold sequencing depth would only examine 10 diploid cell equivalents). In contrast, TagMap enriches the host–virus junctions and can interrogate up to 20,000 cells and is able to detect rare viral retrotranspositions in LINE1 non-overexpressing cells. Although Nanopore WGS is 10–20-fold more sensitive per tested cell, TagMap can interrogate 1000–2000-fold more cells and, therefore, can identify infrequent retrotranspositions. When comparing SARS-CoV-2 infection and viral nucleocapsid mRNA transfection by TagMap, retrotransposed SARS-CoV-2 sequences were only detected in infected but not in transfected cells. Retrotransposition in virus-infected cells, in contrast to transfected cells, may be facilitated because virus infection, in contrast to viral RNA transfection, results in significantly higher viral RNA levels and stimulates LINE1 expression by causing cellular stress.
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- 2023
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4. Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease
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Max Friesen, Raymond Camahort, Youn-Kyoung Lee, Fang Xia, Robert E. Gerszten, Eugene P. Rhee, Rahul C. Deo, and Chad A. Cowan
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human adipocytes ,adipose inflammation ,metabolic disease ,IRF1 ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation.
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- 2017
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5. Hunter-gatherer aggregations writ large: Economy, interaction, and ritual in the final days of the Tuniit (Late Dorset) culture
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Max Friesen, T.
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- 2022
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6. SAA Current Perspectives: Archaeology on the Arctic Rim of North America
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Owen K. Mason, T. Max Friesen and Owen K. Mason, T. Max Friesen
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- 2018
7. Paleogeography of Human Settlement at Iqaluktuuq, Victoria Island, Nunavut
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Julie M. Ross and T. Max Friesen
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sea level ,nunavut ,archaeology ,arctic ,settlement patterns ,Dorset ,Thule ,Inuit human-environment relationship ,environmental archaeology ,General Earth and Planetary Sciences - Abstract
Change in sea levels, be they isostatic or eustatic, impact humans and the paleogeography they inhabit. In this paper we examine paleogeography at Iqaluktuuq, a section of the Ekalluk River, Victoria Island, Nunavut, between Tahiryuaq (Ferguson Lake) and Wellington Bay. The area’s isostatic rebound impacted the Ekalluk River’s development and the use of the area by two essential subsistence resources, Arctic char (Salvelinus alpinus) and caribou (Rangifer tarandus). This, in turn, impacted the choices of Pre-Dorset, Middle and Late Dorset, and Thule/Inuit people regarding site locations. A new relative sea-level curve developed using calibrated radiocarbon dates on marine shells and terrestrial material from archaeological sites is produced for Iqaluktuuq. Based on the data, large scale (1:50,000) paleogeography maps are presented for the period of human occupation of Iqaluktuuq, 3100 calibrated years Before Present (B.P. cal) to present, revealing how paleogeography impacts people’s settlement choices.
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- 2022
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8. Heightened apoptotic priming of vascular cells across tissues and life span predisposes them to cancer therapy–induced toxicities
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Johan K. E. Spetz, Mary H. C. Florido, Cameron S. Fraser, Xingping Qin, Jonathan Choiniere, Stacey J. Yu, Rumani Singh, Max Friesen, Lee L. Rubin, Joe-Elie Salem, Javid J. Moslehi, and Kristopher A. Sarosiek
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Adult ,Multidisciplinary ,Neoplasms ,Longevity ,Induced Pluripotent Stem Cells ,Humans ,Endothelial Cells ,Muscle, Smooth, Vascular ,Cells, Cultured - Abstract
Although major organ toxicities frequently arise in patients treated with cytotoxic or targeted cancer therapies, the mechanisms that drive them are poorly understood. Here, we report that vascular endothelial cells (ECs) are more highly primed for apoptosis than parenchymal cells across many adult tissues. Consequently, ECs readily undergo apoptosis in response to many commonly used anticancer agents including cytotoxic and targeted drugs and are more sensitive to ionizing radiation and BH3 mimetics than parenchymal cells in vivo. Further, using differentiated isogenic human induced pluripotent stem cell models of ECs and vascular smooth muscle cells (VSMCs), we find that these vascular cells exhibit distinct drug toxicity patterns, which are linked to divergent therapy–induced vascular toxicities in patients. Collectively, our results demonstrate that vascular cells are highly sensitive to apoptosis-inducing stress across life span and may represent a “weakest link” vulnerability in multiple tissues for development of toxicities.
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- 2022
9. The Arctic CHAR Project: Climate Change Impacts on the Inuvialuit Archaeological Record
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T. Max Friesen
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archaeology ,climate change ,Arctic ,Inuvialuit ,Mackenzie delta ,Archaeology ,CC1-960 - Abstract
Around the circumpolar North, archaeologists and heritage managers are growing increasingly concerned about the destruction of archaeological sites due to modern climate change. This paper describes the Arctic CHAR project, designed to address this issue in the Mackenzie Delta region of northwestern Canada. The Mackenzie Delta is home to the Inuvialuit, whose rich history is recorded in many coastal sites. Due to permafrost melt and increasing relative sea level, these sites are being destroyed at an alarming rate. Arctic CHAR consists of two main components: survey to assess the condition of heritage resources across the region, and excavation of the most important threatened sites.
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- 2015
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10. Tracing hepatitis B virus (HBV) genotype B5 (formerly B6) evolutionary history in the circumpolar Arctic through phylogeographic modelling
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Remco Bouckaert, Brenna C. Simons, Henrik Krarup, T. Max Friesen, and Carla Osiowy
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Hepatitis B virus ,Genotype ,Evolution ,Arctic ,Inuit ,Host-pathogen balance ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Indigenous populations of the circumpolar Arctic are considered to be endemically infected (>2% prevalence) with hepatitis B virus (HBV), with subgenotype B5 (formerly B6) unique to these populations. The distinctive properties of HBV/B5, including high nucleotide diversity yet no significant liver disease, suggest virus adaptation through long-term host-pathogen association. Methods To investigate the origin and evolutionary spread of HBV/B5 into the circumpolar Arctic, fifty-seven partial and full genome sequences from Alaska, Canada and Greenland, having known location and sampling dates spanning 40 years, were phylogeographically investigated by Bayesian analysis (BEAST 2) using a reversible-jump-based substitution model and a clock rate estimated at 4.1 × 10−5 substitutions/site/year. Results Following an initial divergence from an Asian viral ancestor approximately 1954 years before present (YBP; 95% highest probability density interval [1188, 2901]), HBV/B5 coalescence occurred almost 1000 years later. Surprisingly, the HBV/B5 ancestor appears to locate first to Greenland in a rapid coastal route progression based on the landscape aware geographic model, with subsequent B5 evolution and spread westward. Bayesian skyline plot analysis demonstrated an HBV/B5 population expansion occurring approximately 400 YBP, coinciding with the disruption of the Neo-Eskimo Thule culture into more heterogeneous and regionally distinct Inuit populations throughout the North American Arctic. Discussion HBV/B5 origin and spread appears to occur coincident with the movement of Neo-Eskimo (Inuit) populations within the past 1000 years, further supporting the hypothesis of HBV/host co-expansion, and illustrating the concept of host-pathogen adaptation and balance.
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- 2017
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11. Development of a physiological insulin resistance model in human stem cell–derived adipocytes
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Max Friesen, Andrew S. Khalil, M. Inmaculada Barrasa, Jacob F. Jeppesen, David J. Mooney, and Rudolf Jaenisch
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Glucose ,Multidisciplinary ,Diabetes Mellitus, Type 2 ,Stem Cells ,Adipocytes ,Humans ,Insulin ,Insulin Resistance - Abstract
Adipocytes are key regulators of human metabolism, and their dysfunction in insulin signaling is central to metabolic diseases including type II diabetes mellitus (T2D). However, the progression of insulin resistance into T2D is still poorly understood. This limited understanding is due, in part, to the dearth of suitable models of insulin signaling in human adipocytes. Traditionally, adipocyte models fail to recapitulate in vivo insulin signaling, possibly due to exposure to supraphysiological nutrient and hormone conditions. We developed a protocol for human pluripotent stem cell–derived adipocytes that uses physiological nutrient conditions to produce a potent insulin response comparable to in vivo adipocytes. After systematic optimization, this protocol allows robust insulin-stimulated glucose uptake and transcriptional insulin response. Furthermore, exposure of sensitized adipocytes to physiological hyperinsulinemia dampens insulin-stimulated glucose uptake and dysregulates insulin-responsive transcription. Overall, our methodology provides a novel platform for the mechanistic study of insulin signaling and resistance using human pluripotent stem cell–derived adipocytes.
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- 2022
12. An Igluryuaq Unearthed: A Pre-Contact Inuvialuit Cruciform House from Arctic Canada
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T. Max Friesen and Rémi Méreuze
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Delta ,010506 paleontology ,Archeology ,060102 archaeology ,Ethnohistory ,06 humanities and the arts ,Complex type ,01 natural sciences ,Archaeology ,Geography ,Cruciform ,Arctic ,0601 history and archaeology ,0105 earth and related environmental sciences - Abstract
Across the North American Arctic, Inuit societies constructed a broad array of sophisticated dwellings. One particularly large and complex type known from the Mackenzie Delta region is the crucifor...
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- 2020
13. Climate variability of the Common Era (AD 1–2000) in the eastern North American Arctic: Impacts on human migrations
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Andrew S. Medeiros, Sarah A. Finkelstein, and T. Max Friesen
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010506 paleontology ,education.field_of_study ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Human migration ,business.industry ,Population ,Climate change ,15. Life on land ,01 natural sciences ,Geography ,Arctic ,13. Climate action ,Effects of global warming ,Paleoclimatology ,Archipelago ,Physical geography ,education ,business ,Roman Warm Period ,0105 earth and related environmental sciences ,Earth-Surface Processes - Abstract
The eastern North American Arctic has a complex 5000-year prehistory, during which many human population movements occurred over great distances. Archaeologists have interpreted these movements as resulting from many factors, however the effects of climate change are often hypothesized as primary drivers that can “push” human groups to leave some regions, or “pull” them to move to others. Here, we examine climate change at the regional scale over the Common Era using Arctic paleoclimate data derived from a wide suite of biological proxies and geochemical tracers. We consider available statistical composites of high resolution (sub-decadal) paleo-temperature reconstructions for the Arctic region, as well as local-scale reconstructions at century or sub-century scale resolution in three focal regions of archaeological significance relevant to population movements: Victoria Island, Foxe Basin/Baffin Island, and the High Arctic (Ellesmere Island/Northwestern Greenland). We emphasize the two most widespread, though variable, climate change events characteristic of this period: the Medieval Climatic Anomaly and Little Ice Age in the second millennium AD; we also evaluate the evidence for the Roman Warm Period and Dark Ages Cold Period in the first millennium AD, as context for later events. We integrate information on the timing and magnitude of these events across the Canadian Arctic Archipelago, and assess the degree to which they coincide with current understanding of major population movements, with particular emphasis on three migration episodes. First, the expansion of Late Dorset Paleo-Inuit to the Central and High Arctic beginning in the late first millennium AD is plausibly linked to warming temperatures of the MCA. Second, the migration of Thule Inuit from Alaska to the Eastern Arctic beginning ca AD 1250 is not linked to warmer temperatures as previously hypothesized, and is therefore more likely related to social factors in Alaska. Third, the abandonment of northern regions and new settlement of southern regions by Inuit in the mid-second millennium AD is likely linked to a combination of cooling climate and increasing availability of European trade goods. Together, these three case studies indicate that linkages between climate change and migration are complex, variable, and mediated through social and economic factors.
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- 2020
14. Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes
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Haojie Yu, John L. Rinn, Chad A. Cowan, Takafumi Toyohara, Benjamin D. Pope, Qiurong Ding, Curtis R. Warren, Max Friesen, Mary H.C. Florido, Loyal A. Goff, and Carolyn Sayre
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0301 basic medicine ,mitochondrial metabolism ,MTLN ,Cell Respiration ,Mitochondrial trifunctional protein ,adipocyte ,Biochemistry ,Article ,Cell Line ,Mitochondrial Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adipocyte ,Adipocytes ,Genetics ,Animals ,Humans ,Lipolysis ,Amino Acid Sequence ,Gene ,Conserved Sequence ,Mice, Knockout ,biology ,Triglyceride ,Cell Biology ,Lipid Metabolism ,metabolic disease ,Lipids ,human stem cells ,Phenotype ,Mitochondria ,Cell biology ,030104 developmental biology ,chemistry ,Adipogenesis ,Knockout mouse ,biology.protein ,Energy Metabolism ,Oxidation-Reduction ,metabolism ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Summary We previously discovered in mouse adipocytes an lncRNA (the homolog of human LINC00116) regulating adipogenesis that contains a highly conserved coding region. Here, we show human protein expression of a peptide within LINC00116, and demonstrate that this peptide modulates triglyceride clearance in human adipocytes by regulating lipolysis and mitochondrial β-oxidation. This gene has previously been identified as mitoregulin (MTLN). We conclude that MTLN has a regulatory role in adipocyte metabolism as demonstrated by systemic lipid phenotypes in knockout mice. We also assert its adipocyte-autonomous phenotypes in both isolated murine adipocytes as well as human stem cell-derived adipocytes. MTLN directly interacts with the β subunit of the mitochondrial trifunctional protein, an enzyme critical in the β-oxidation of long-chain fatty acids. Our human and murine models contend that MTLN could be an avenue for further therapeutic research, albeit not without caveats, for example, by promoting white adipocyte triglyceride clearance in obese subjects., Highlights • MTLN is expressed in human stem cell-derived adipocytes and murine adipose tissue • MTLN localizes to mitochondria and associates with mitochondrial trifunctional enzyme • Adipocytes display decreased fatty acid oxidation upon MTLN knockout • MTLN KO affects murine serum lipid levels and adipocyte triglyceride accumulation, Cowan and colleagues have demonstrated the expression of mitoregulin (MTLN) in murine adipose tissue as well as human stem cell-derived adipocytes. MTLN affects triglyceride accumulation and lipolysis in adipocytes. It does so through mitochondrial localization and interaction with complexes involved in fatty acid oxidation.
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- 2020
15. Radiocarbon Evidence for Fourteenth-Century Dorset Occupation in the Eastern North American Arctic
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T. Max Friesen
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010506 paleontology ,Archeology ,History ,geography ,060102 archaeology ,Museology ,Significant part ,Victoria island ,06 humanities and the arts ,Hiatus ,01 natural sciences ,Archaeology ,law.invention ,Arts and Humanities (miscellaneous) ,Arctic ,law ,Population Distributions ,geography.geographical_feature ,Period (geology) ,0601 history and archaeology ,Radiocarbon dating ,0105 earth and related environmental sciences - Abstract
One of the most persistent debates in the archaeology of the North American Arctic relates to thirteenth-century AD population distributions and movements. Around this time, the final culture of the long-lived Paleo-Inuit tradition, known as Late Dorset, was replaced by Thule Inuit, who migrated from Alaska to the Eastern Arctic. Due to the almost complete lack of evidence for direct interaction between Dorset and Thule, there are currently two contrasting models for this transitional period. The first proposes a temporal hiatus between Late Dorset and Thule during which the Eastern Arctic was unoccupied. The second proposes that Late Dorset persisted to at least the late thirteenth century and still occupied some regions of the Eastern Arctic when Thule arrived. Resolution of this question depends largely on radiocarbon dates, particularly for the poorly understood Late Dorset period. This article presents 56 new AMS radiocarbon dates from three Late Dorset sites in the Iqaluktuuq region of southeastern Victoria Island in the Central Arctic. They resolve a significant part of the debate by confirming that Dorset settlement continued in this region later than AD 1300, thus overlapping with Thule settlement in adjacent regions for decades, and perhaps as much as a century.
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- 2019
16. SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
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Alexsia Richards, Max Friesen, Andrew Khalil, M. Inmaculada Barrasa, Lee Gehrke, and Rudolf Jaenisch
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Multidisciplinary - Abstract
Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.
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- 2021
17. Ancestral landscapes
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Max Friesen
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- 2021
18. Hunter-gatherer aggregations writ large: Economy, interaction, and ritual in the final days of the Tuniit (Late Dorset) culture
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T. Max Friesen
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Archeology ,History ,Human Factors and Ergonomics - Published
- 2022
19. Looking back while moving forward: How past responses to climate change can inform future adaptation and mitigation strategies in the Arctic
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Peter Jordan, Sean P.A. Desjardins, T. Max Friesen, and Arctic and Antarctic studies
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010506 paleontology ,Coping (psychology) ,Food security ,Global warming ,Climate change ,010502 geochemistry & geophysics ,01 natural sciences ,Indigenous ,The arctic ,Arctic ,Political science ,Environmental planning ,0105 earth and related environmental sciences ,Earth-Surface Processes ,Economic change - Abstract
Modern Arctic Indigenous peoples face many interconnected pressures, not the least of which is anthropogenic climate change, which is emerging as one of the most dramatic drivers of social and economic change in recent memory. In this paper, we investigate whether or not insights into premodern strategies for coping with climate change—and especially the “deeper histories” of traditional ways-of-knowing—can play a useful role in future planning, management and mitigation efforts. We do this in two ways. First, we assess this special issue's 17 archaeological case studies, in order to determine whether they are conducted within a framework that is consistent with approaches to resilience in studies of modern Arctic communities. Second, we focus on three climate-driven challenges faced by Canadian Arctic Inuit: safe travel, food security and food safety. For each, we identify specific ways in which studies of past social-ecological systems intersect with modern climate adaptation. We conclude that since archaeological insights highlight the operation of decision-making processes within long-term culture-adaptive trajectories, they can offer unique insights into the much shorter-term processes currently underway. While we highlight many potential directions for productive collaboration, much more work is required in local and regional settings to demonstrate the full potential of archaeology for future-oriented planning and mitigation efforts.
- Published
- 2020
20. Modeling the Effects of Severe Metabolic Disease by Genome Editing of hPSC-Derived Endothelial Cells Reveals an Inflammatory Phenotype
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Gregor Dernick, Chad A. Cowan, Natalie Bordag, Jitao David Zhang, Claas A. Meyer, Antje Wagner-Golbs, Max Friesen, Mark Burcin, Martin Ebeling, Yanjun Lan, Martin Graf, Christoph Patsch, Klaus Christensen, Filip Roudnicky, and Andreas Staempfli
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Pluripotent Stem Cells ,Chemokine ,Inflammation ,Biology ,Models, Biological ,Article ,Catalysis ,endothelial dysfunction ,Proinflammatory cytokine ,Inorganic Chemistry ,Downregulation and upregulation ,medicine ,Humans ,genome editing ,Physical and Theoretical Chemistry ,Endothelial dysfunction ,Induced pluripotent stem cell ,Molecular Biology ,Spectroscopy ,Gene Editing ,Metabolic Syndrome ,AKT2 ,Organic Chemistry ,Endothelial Cells ,General Medicine ,pluripotent-stem-cell-derived endothelial cells ,medicine.disease ,Computer Science Applications ,Endothelial stem cell ,Insulin receptor ,inflammation ,Gene Knockdown Techniques ,biology.protein ,Cancer research ,medicine.symptom - Abstract
The kinase AKT2 (PKB) is an important mediator of insulin signaling, for which loss-of-function knockout (KO) mutants lead to early onset diabetes mellitus, and dominant active mutations lead to early development of obesity and endothelial cell (EC) dysfunction. To model EC dysfunction, we used edited human pluripotent stem cells (hPSCs) that carried either a homozygous deletion of AKT2 (AKT2 KO) or a dominant active mutation (AKT2 E17K), which, along with the parental wild type (WT), were differentiated into ECs. Profiling of EC lines indicated an increase in proinflammatory and a reduction in anti-inflammatory fatty acids, an increase in inflammatory chemokines in cell supernatants, increased expression of proinflammatory genes, and increased binding to the EC monolayer in a functional leukocyte adhesion assay for both AKT2 KO and AKT2 E17K. Collectively, these findings suggest that vascular endothelial inflammation that results from dysregulated insulin signaling (homeostasis) may contribute to coronary artery disease, and that either downregulation or upregulation of the insulin pathway may lead to inflammation of endothelial cells. This suggests that the standard of care for patients must be expanded from control of metabolic parameters to include control of inflammation, such that endothelial dysfunction and cardiovascular disorders can ultimately be prevented.
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- 2019
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21. Technology, Taphonomy, and Seasonality: Understanding Differences between Dorset and Thule Subsistence Strategies at Iqaluktuuq, Victoria Island
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T. Max Friesen and Lesley Howse
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010506 paleontology ,Taphonomy ,060102 archaeology ,Ecology ,Victoria island ,Subsistence agriculture ,Subsistence economy ,06 humanities and the arts ,Seasonality ,medicine.disease ,01 natural sciences ,Predation ,Geography ,Arctic ,geography.geographical_feature ,medicine ,0601 history and archaeology ,Ecology, Evolution, Behavior and Systematics ,Zooarchaeology ,0105 earth and related environmental sciences - Abstract
This paper examines differences between Late Dorset and Thule Inuit subsistence economies at the Bell site on Victoria Island, Nunavut. This location is relatively unusual in the eastern Arctic region because local subsistence was based largely on caribou and fish, rather than the sea mammals that dominate in most other regions. For both periods, animal bone samples are quantified in terms of taxonomic frequencies, element (body part) distributions, seasonality, prey demography, and bone modifications such as cutting, burning, and gnawing. A comparison between the periods indicates many broad similarities in subsistence, but some subtle differences suggest that the Thule had a more focal and specialized economy, with a slightly different seasonal profile.
- Published
- 2017
22. A coagulation defect arising from heterozygous premature termination of tissue factor
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Sol Schulman, Emale El-Darzi, Kathelijne Peerlinck, Chad A. Cowan, Calvin R. Schuster, Marisa A Brake, Mary H.C. Florido, Robert Flaumenhaft, Ernest Turro, Max Friesen, Nihr BioResource, Kathleen Freson, Willem H. Ouwehand, Glenn Merrill-Skoloff, Bruce Furie, Randal J. Westrick, and Lin Lin
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0301 basic medicine ,Male ,medicine.medical_specialty ,Heterozygote ,Vascular smooth muscle ,Induced Pluripotent Stem Cells ,Haploinsufficiency ,Frameshift mutation ,Thromboplastin ,03 medical and health sciences ,Tissue factor ,Mice ,0302 clinical medicine ,Blood Coagulation Disorders, Inherited ,Internal medicine ,medicine ,Animals ,Humans ,Thrombus ,Frameshift Mutation ,Gene Editing ,Mice, Knockout ,Hematology ,Base Sequence ,business.industry ,Abnormal bleeding ,General Medicine ,Peptide Chain Termination, Translational ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Phenotype ,Coagulation ,Codon, Nonsense ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business ,Research Article - Abstract
Tissue factor (TF) is the primary initiator of blood coagulation in vivo and the only blood coagulation factor for which a human genetic defect has not been described. As there are no routine clinical assays that capture the contribution of endogenous TF to coagulation initiation, the extent to which reduced TF activity contributes to unexplained bleeding is unknown. Using whole genome sequencing, we identified a heterozygous frameshift variant (p.Ser117HisfsTer10) in F3, the gene encoding TF, causing premature termination of TF ("TFshort") in a woman with unexplained bleeding. Routine hematological laboratory evaluation of the proposita was normal. CRISPR-edited human induced pluripotent stem cells recapitulating the variant were differentiated into vascular smooth muscle and endothelial cells that demonstrated haploinsufficiency of TF. The variant F3 transcript is eliminated by nonsense-mediated decay. Neither overexpression nor addition of exogenous recombinant TFshort inhibited factor Xa or thrombin generation, excluding a dominant negative mechanism. F3+/- mice provide an animal model of TF haploinsufficiency and exhibited prolonged bleeding times, impaired thrombus formation, and reduced survival following major injury. Heterozygous TF deficiency is present in at least 1 in 25,000 individuals and could limit coagulation initiation in undiagnosed individuals with abnormal bleeding but a normal routine laboratory evaluation.
- Published
- 2019
23. Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis
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Toshiaki Nakano, Shunsuke Katsuki, Chad A. Cowan, Max Friesen, Takafumi Toyohara, Minjin Lee, Haojie Yu, Masanori Aikawa, Lee L. Rubin, Alexandre C. Pereira, Takaaki Abe, Torsten B. Meissner, Leon M. Ptaszek, Mary H.C. Florido, Lance S. Davidow, and Filip Roudnicky
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Apolipoprotein E ,medicine.medical_specialty ,Vascular smooth muscle ,Cell ,Induced Pluripotent Stem Cells ,Myocytes, Smooth Muscle ,Biology ,Article ,Muscle, Smooth, Vascular ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Lipid droplet ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Cholesterol ,Cell migration ,Lipid metabolism ,Cell Biology ,musculoskeletal system ,Atherosclerosis ,Endothelial stem cell ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Diabetes Mellitus, Type 2 ,cardiovascular system ,Cancer research ,Molecular Medicine ,Stem cell ,Arylacetamide deacetylase ,biology.gene ,030217 neurology & neurosurgery - Abstract
Although susceptibility to cardiovascular disease (CVD) is different for every patient, why some patients with type 2 diabetes mellitus (T2DM) develop CVD while others are protected has not yet been clarified. Using T2DM-patient-derived human induced pluripotent stem cells (hiPSCs), we found that in patients protected from CVD, there was significantly elevated expression of an esterase, arylacetamide deacetylase (AADAC), in vascular smooth muscle cells (VSMCs). We overexpressed this esterase in human primary VSMCs and VSMCs differentiated from hiPSCs and observed that the number of lipid droplets was significantly diminished. Further metabolomic analyses revealed a marked reduction in storage lipids and an increase in membrane phospholipids, suggesting changes in the Kennedy pathway of lipid bioassembly. Cell migration and proliferation were also significantly decreased in AADAC-overexpressing VSMCs. Moreover, apolipoprotein E (Apoe)-knockout mice overexpressing VSMC-specific Aadac showed amelioration of atherosclerotic lesions. Our findings suggest that higher AADAC expression in VSMCs protects T2DM patients from CVD.
- Published
- 2019
24. Palaeo-Eskimo genetic ancestry and the peopling of Chukotka and North America
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Denise Keating, N. Ezgi Altınışık, Thiseas Christos Lamnidis, Jonas Oppenheimer, Pavel Flegontov, Elizaveta Veselovskaya, Johannes Krause, Alexander M. Kim, Nicole Adamski, Thomas K. Harper, Piya Changmai, Francesca Candilio, Douglas J. Kennett, Ron Pinhasi, M. Geoffrey Hayes, Jennifer Raff, Brendan J. Culleton, Ben A. Potter, Choongwon Jeong, T. Max Friesen, Olga Flegontova, David Reich, Nadin Rohland, Pontus Skoglund, Robert A. Sattler, Ann Marie Lawson, Edward J. Vajda, Swapan Mallick, Iñigo Olalde, Sergey Vasilyev, Dennis H. O'Rourke, Nasreen Broomandkhoshbacht, Kristin Stewardson, Stephan Schiffels, and Deborah A. Bolnick
- Subjects
0303 health sciences ,education.field_of_study ,peopling of Chukotka and North America ,Multidisciplinary ,060102 archaeology ,Native american ,Genetic genealogy ,Population ,Population genetics ,Genetic relationship ,06 humanities and the arts ,Palaeo-Eskimo ,Article ,ancient DNA ,03 medical and health sciences ,Phylogeography ,Geography ,Arctic ,Ethnology ,0601 history and archaeology ,education ,Holocene ,030304 developmental biology - Abstract
Much of the American Arctic was first settled 5,000 years ago, by groups of people known as Palaeo-Eskimos. They were subsequently joined and largely displaced around 1,000 years ago by ancestors of the present-day Inuit and Yup’ik1–3. The genetic relationship between Palaeo-Eskimos and Native American, Inuit, Yup’ik and Aleut populations remains uncertain4–6. Here we present genomic data for 48 ancient individuals from Chukotka, East Siberia, the Aleutian Islands, Alaska, and the Canadian Arctic. We co-analyse these data with data from present-day Alaskan Inupiat and West Siberian populations and published genomes. Using methods based on rare-allele and haplotype sharing, as well as established techniques4,7–9, we show that Palaeo-Eskimo-related ancestry is ubiquitous among people who speak Na-Dene and Eskimo–Aleut languages. We develop a comprehensive model for the Holocene peopling events of Chukotka and North America, and show that Na-Dene-speaking peoples, people of the Aleutian Islands, and Yup’ik and Inuit across the Arctic region all share ancestry from a single Palaeo-Eskimo-related Siberian source. DNA analysis of ancient individuals and modern populations suggests that the population history of North America can be explained by the admixture of two ancestral lineages—Palaeo-Eskimos and First Peoples.
- Published
- 2019
25. Bjarne Grønnow . The frozen Saqqaq sites of Disko Bay, West Greenland. Qeqertasussuk and Qajaa (2400–900 BC). 2017. 490 pages, 106 colour and 210 b&w illustrations, 30 tables. Copenhagen & Chicago (IL): Museum Tusculanum Press & University of Chicago Press; 978-87-635-4561-7 hardback $70
- Author
-
T. Max Friesen
- Subjects
Archeology ,Geography ,General Arts and Humanities ,Bay ,Archaeology - Published
- 2017
26. Asialoglycoprotein receptor 1 is a specific cell-surface marker for isolating hepatocytes derived from human pluripotent stem cells
- Author
-
Chad A. Cowan, Christopher A. Henderson, Max Friesen, Fang Xia, Kiran Musunuru, Derek T. Peters, Caroline E. Becker, and Curtis R. Warren
- Subjects
0301 basic medicine ,Induced Pluripotent Stem Cells ,Population ,Asialoglycoprotein Receptor ,Biology ,Cell Line ,Transcriptome ,03 medical and health sciences ,Directed differentiation ,Albumins ,Gene expression ,medicine ,Humans ,Urea ,Induced pluripotent stem cell ,education ,Molecular Biology ,Embryonic Stem Cells ,education.field_of_study ,Cell Membrane ,Cell Differentiation ,Flow Cytometry ,Stem Cells and Regeneration ,Molecular biology ,In vitro ,030104 developmental biology ,medicine.anatomical_structure ,Hepatocyte ,Hepatocytes ,Cytochromes ,Asialoglycoprotein receptor ,Developmental Biology - Abstract
Hepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. Increased differentiation efficiency and more accurate approximation of the in vivo hepatocyte gene expression profile would improve the utility of hPSCs. Towards this goal, we demonstrate the purification of a subpopulation of functional HLCs using the hepatocyte surface marker asialoglycoprotein receptor 1 (ASGR1). We analyzed the expression profile of ASGR1-positive cells by microarray, and tested their ability to perform mature hepatocyte functions (albumin and urea secretion, cytochrome activity). By these measures, ASGR1-positive HLCs are enriched for the gene expression profile and functional characteristics of primary hepatocytes compared with unsorted HLCs. We have demonstrated that ASGR1-positive sorting isolates a functional subpopulation of HLCs from among the heterogeneous cellular population produced by directed differentiation.
- Published
- 2016
27. Adipocyte Metabolism and Insulin Signaling Perturbations: Insights from Genetics
- Author
-
Max Friesen and Chad A. Cowan
- Subjects
Endocrinology, Diabetes and Metabolism ,Regulator ,Adipose tissue ,030209 endocrinology & metabolism ,Genome-wide association study ,Type 2 diabetes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Adipocyte ,Adipocytes ,Medicine ,Animals ,Humans ,Insulin ,Obesity ,Genetics ,biology ,business.industry ,medicine.disease ,Insulin receptor ,chemistry ,biology.protein ,Insulin Resistance ,business ,Genome-Wide Association Study - Abstract
Insulin resistance (IR) is a rapidly growing pandemic. It poses an enormous health burden given its comorbidity with obesity, type 2 diabetes (T2D), and other metabolic and cardiovascular diseases (CVDs). Adipose tissue has been established as a key regulator of whole-body metabolic homeostasis, with interest growing rapidly. Emerging evidence suggests that adipocytes play an important role in these afflictions and contribute to IR. Genome-wide association studies (GWAS) have begun to illuminate the genetics underlying obesity, T2D, and IR, and this will allow further study into the disease mechanisms of the genes implicated in these metabolic diseases. Progress towards understanding the molecular mechanisms underlying diseased adipocytes will be discussed here, with an eye towards the future in developing novel therapeutics to combat metabolic disease.
- Published
- 2018
28. Climate change and the deteriorating archaeological and environmental archives of the Arctic
- Author
-
Jørgen Hollesen, Rasmus Fenger-Nielsen, T. Max Friesen, Anne M. Jensen, Tom Dawson, Adam Markham, Vladimir V. Pitulko, Vibeke Vandrup Martens, Martin Callanan, Marcy Rockman, University of St Andrews. School of History, and University of St Andrews. Scottish Oceans Institute
- Subjects
010506 paleontology ,Archeology ,Arts and Humanities(all) ,archaeological mitigation strategies ,T-NDAS ,Climate change ,Conservation ,Archaeological mitigation strategies ,Permafrost ,01 natural sciences ,Arctic ,Climate of the Arctic ,Effects of global warming ,SDG 13 - Climate Action ,Cultural heritage management ,0601 history and archaeology ,Heritage management ,0105 earth and related environmental sciences ,060102 archaeology ,General Arts and Humanities ,conservation ,06 humanities and the arts ,CC Archaeology ,CC ,Archaeology ,The arctic ,Coastal erosion ,Geography ,climate change ,heritage management - Abstract
Hollesen and Fenger-Nielsen thank VELUX FONDEN (33813) and the Danish National Research Foundation (CENPERM DNRF100) for financial support, as well as colleagues at the National Museum of Denmark and Greenland National Museum. Callanan thanks the Norwegian Research Council (Miljø 2015) for post-doctoral funding. Dawson thanks Historic Environment Scotland. Markham thanks the J.M. Kaplan Fund, the Barr Foundation and the Rockefeller Brothers Fund. Martens thanks The Research Council of Norway for funding project 212900. Pitulko thanks the Russian Science Foundation for supporting project 16-18-10265-RNF. The cold, wet climate of the Arctic has led to the extraordinary preservation of archaeological sites and materials that offer important contributions to the understanding of our common cultural and ecological history. This potential, however, is quickly disappearing due to climate-related variables, including the intensification of permafrost thaw and coastal erosion, which are damaging and destroying a wide range of cultural and environmental archives around the Arctic. In providing an overview of the most important effects of climate change in this region and on archaeological sites, the authors propose the next generation of research and response strategies, and suggest how to capitalise on existing successful connections among research communities and between researchers and the public. Publisher PDF
- Published
- 2018
29. Out of the Cold : Archaeology on the Arctic Rim of North America
- Author
-
Owen K. Mason, T. Max Friesen, Owen K. Mason, and T. Max Friesen
- Subjects
- Arctic peoples--Antiquities, Prehistoric peoples--Arctic regions, Excavations (Archaeology)--Arctic regions, Social archaeology--Arctic regions
- Abstract
The Arctic rim of North America presents one of the most daunting environments for humans. Cold and austere, it is lacking in plants but rich in marine mammals-primarily the ringed seal, walrus, and bowhead whale. In this book in the SAA Press Current Perspectives Series, the authors track the history of cultural innovations in the Arctic and Subarctic for the past 12,000 years, including the development of sophisticated architecture, watercraft, fur clothing, hunting technology, and worldviews. Climate change is linked to many of the successes and failures of its inhabitants; warming or cooling periods led to periods of resource abundance or collapse, and in several instances to long-distance migrations. At its western and eastern margins, the Arctic also experienced the impact of Asian and European world systems, from that of the Norse in the East to the Russians in the Bering Strait.
- Published
- 2017
30. FPLD2 LMNA mutation R482W dysregulates iPSC-derived adipocyte function and lipid metabolism
- Author
-
Chad A. Cowan and Max Friesen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Induced Pluripotent Stem Cells ,Biophysics ,Adipose tissue ,Biology ,Biochemistry ,LMNA ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Adipocyte ,Internal medicine ,medicine ,Adipocytes ,Autophagy ,Humans ,Point Mutation ,Molecular Biology ,Cells, Cultured ,Triglycerides ,Adipogenesis ,Hypertriglyceridemia ,Lipid metabolism ,Cell Biology ,medicine.disease ,Lamin Type A ,Lipid Metabolism ,Lipodystrophy, Familial Partial ,030104 developmental biology ,Endocrinology ,chemistry ,Lipodystrophy ,Insulin Resistance ,030217 neurology & neurosurgery - Abstract
Lipodystrophies are disorders that directly affect lipid metabolism and storage. Familial partial lipodystrophy type 2 (FPLD2) is caused by an autosomal dominant mutation in the LMNA gene. FPLD2 is characterized by abnormal adipose tissue distribution. This leads to metabolic deficiencies, such as insulin-resistant diabetes mellitus and hypertriglyceridemia. Here we have derived iPSC lines from two individuals diagnosed with FPLD2, and differentiated these cells into adipocytes. Adipogenesis and certain adipocyte functions are impaired in FPLD2-adipocytes. Consistent with the lipodystrophic phenotype, FPLD2-adipocytes appear to accumulate markers of autophagy and catabolize triglycerides at higher levels than control adipocytes. These data are suggestive of a mechanism causing the lack of adipose tissue in FPLD2 patients.
- Published
- 2017
31. Documenter par la 3D un site en contexte arctique, entre recherche archéologique et changements environnementaux : Kuukpak, Territoires du Nord-Ouest, Canada
- Author
-
Rémi Méreuze, Pete Dawson, T. Max Friesen, and Adam Jarhaus
- Subjects
General Medicine - Abstract
Dans l'Arctique canadien, comme dans l'ensemble du monde septentrional, les recents changements climatiques ont grandement affecte l'environnement. Les sous-sols geles fondent, le niveau moyen des mers augmente et l'erosion est accrue un peu plus chaque annee. Dans ce contexte sensible, le projet Arctic CHAR a pour mission de sauvegarder au mieux le patrimoine inuvialuit du delta du Mackenzie. Parallelement au monitorat des cotes et a la prospection, le site de Kuukpak fait l'objet de fouilles depuis l'ete 2014. La structure fouillee, une maison principalement composee de bois, est fragile, le bois commencant a se decomposer des sa mise au jour, et complexe, l'effondrement de la charpente ayant abouti a l'amalgame de ces pieces structurelles. Deux methodes de releve 3D ont ete utilisees pour soutenir cette operation de fouille, la lasergrammetrie et la photogrammetrie. La premiere, dans le but de conserver le plus fidelement possible ce patrimoine voue a la destruction ; la deuxieme pour assurer un enregistrement regulier durant l'avancee des fouilles.
- Published
- 2017
32. Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease
- Author
-
Chad A. Cowan, Eugene P. Rhee, Fang Xia, Robert E. Gerszten, Rahul C. Deo, Raymond Camahort, Youn-Kyoung Lee, and Max Friesen
- Subjects
0301 basic medicine ,Nude ,Adipose tissue ,Biochemistry ,Transcriptome ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Adipocyte ,Adipocytes ,2.1 Biological and endogenous factors ,Aetiology ,lcsh:QH301-705.5 ,Cells, Cultured ,lcsh:R5-920 ,Cultured ,Diabetes ,metabolic disease ,Phenotype ,Cell biology ,Up-Regulation ,HIV/AIDS ,Female ,medicine.symptom ,lcsh:Medicine (General) ,Cells ,1.1 Normal biological development and functioning ,Clinical Sciences ,Mice, Nude ,030209 endocrinology & metabolism ,Inflammation ,Biology ,Mesenchymal Stem Cell Transplantation ,Article ,03 medical and health sciences ,Mediator ,Downregulation and upregulation ,Underpinning research ,medicine ,Genetics ,Animals ,Humans ,Obesity ,human adipocytes ,Metabolic and endocrine ,Nutrition ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,IRF1 ,Cell Biology ,adipose inflammation ,030104 developmental biology ,lcsh:Biology (General) ,chemistry ,Immunology ,Biochemistry and Cell Biology ,Developmental Biology ,Interferon Regulatory Factor-1 - Abstract
Summary The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation., Graphical Abstract, Highlights • Primary human adipocytes strongly express IRF1 compared with ASC adipocytes • ASC adipocytes expressing IRF1 exhibit phenotypes associated with metabolic disease • Adipocyte IRF1 level in vivo leads to recruitment of pro-inflammatory macrophages • Comparison of in vivo and in vitro adipose inflammation and metabolic phenotypes, In this report, Cowan and colleagues decipher the transcriptional underpinnings of low-grade adipose inflammation. Employing comparative transcriptomics analysis of primary human adipocytes and genetically matched in vitro differentiated counterparts, IRF1 was identified as a mediator of adipocyte inflammatory phenotypes. Both in vitro and in vivo IRF1 expression in adipocytes contributed to upregulation of inflammation.
- Published
- 2017
33. Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease
- Author
-
Eilene Duberow, Alexander Meissner, Derek T. Peters, Poching Liu, Jihoon Choi, Xiaoling Zhang, Curtis R. Warren, Max Friesen, Mary H.C. Florido, Caroline E. Becker, Chad A. Cowan, Jun Zhu, Fang Xia, Robert E. Gerszten, Sekar Kathiresan, Xu Shi, Lauren Comisar, Ramachandran S. Vasan, Laurence Daheron, Alexander M. Tsankov, Jennifer Shay, Yoshiyuki Wakabayashi, Kiran Musunuru, John F. O'Sullivan, Jordan Morningstar, Rahul C. Deo, Xin Jiang, and Christopher J. O'Donnell
- Subjects
0301 basic medicine ,Genotype ,Population ,Adipocytes, White ,Induced Pluripotent Stem Cells ,Quantitative Trait Loci ,Down-Regulation ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Transcriptome ,Cohort Studies ,03 medical and health sciences ,Metabolomics ,Metabolic Diseases ,Genetics ,Humans ,Induced pluripotent stem cell ,education ,Genetic association ,education.field_of_study ,Models, Genetic ,Sequence Analysis, RNA ,Reproducibility of Results ,Cell Differentiation ,Cell Biology ,Cellular Reprogramming ,Lipid Metabolism ,Phenotype ,Tissue Donors ,030104 developmental biology ,Chromosomes, Human, Pair 1 ,Hepatocytes ,Leukocytes, Mononuclear ,Molecular Medicine ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.
- Published
- 2017
34. An Early Inupiaq Occupation: Observations on a Thule House From Cape Espenberg, Alaska
- Author
-
Owen K. Mason, Claire Alix, T. Max Friesen, Michael J. E. O’Rourke, and Lauren E.Y. Norman
- Subjects
alaska ,010506 paleontology ,Archeology ,History ,060102 archaeology ,wood architecture ,06 humanities and the arts ,Conservation ,01 natural sciences ,Archaeology ,Inupiaq ,language.human_language ,kotzebue sound ,Education ,thule ,dwelling ,Classical archaeology ,zooarchaeology ,Cape ,language ,0601 history and archaeology ,CC1-960 ,Zooarchaeology ,0105 earth and related environmental sciences - Abstract
This paper describes and interprets a well-preserved early Thule semi-subterranean dwelling from Cape Espenberg, Alaska. The house architecture is similar in many respects to other early Thule dwellings with a sub-rectangular main room, long sunken entrance tunnel, and associated kitchen area. However, the presence of narrow side benches and associated flooring differences adds significantly to the variability present in Thule house form. Radiocarbon dates indicate occupations spanning 1300 to 1450 cal CE. Wood analysis suggests that the house underwent at least one rebuilding episode, which seems to have extended the house occupation into the early 15th century. People acquired mostly small seals for their subsistence, but supplemented their diets in the spring and fall with migrating birds, fish, terrestrial mammals, and other marine mammals. This house represents a fairly typical early Thule coastal winter occupation, but careful excavation of a well-preserved house reveals interesting details in house form, wood use, and subsistence patterns.
- Published
- 2017
35. Tracing hepatitis B virus (HBV) genotype B5 (formerly B6) evolutionary history in the circumpolar Arctic through phylogeographic modelling
- Author
-
Carla Osiowy, Remco R. Bouckaert, T. Max Friesen, Brenna C. Simons, and Henrik Krarup
- Subjects
0301 basic medicine ,Hepatitis B virus ,Host-pathogen balance ,Genotype ,Evolution ,Population ,lcsh:Medicine ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Nucleotide diversity ,03 medical and health sciences ,Arctic ,Virology ,medicine ,Journal Article ,Adaptation ,education ,education.field_of_study ,Ecology ,General Neuroscience ,lcsh:R ,Computational Biology ,General Medicine ,Circumpolar star ,Before Present ,Evolutionary Studies ,Phylogeography ,030104 developmental biology ,Infectious Diseases ,Evolutionary biology ,Inuit ,General Agricultural and Biological Sciences - Abstract
BackgroundIndigenous populations of the circumpolar Arctic are considered to be endemically infected (>2% prevalence) with hepatitis B virus (HBV), with subgenotype B5 (formerly B6) unique to these populations. The distinctive properties of HBV/B5, including high nucleotide diversity yet no significant liver disease, suggest virus adaptation through long-term host-pathogen association.MethodsTo investigate the origin and evolutionary spread of HBV/B5 into the circumpolar Arctic, fifty-seven partial and full genome sequences from Alaska, Canada and Greenland, having known location and sampling dates spanning 40 years, were phylogeographically investigated by Bayesian analysis (BEAST 2) using a reversible-jump-based substitution model and a clock rate estimated at 4.1 × 10−5substitutions/site/year.ResultsFollowing an initial divergence from an Asian viral ancestor approximately 1954 years before present (YBP; 95% highest probability density interval [1188, 2901]), HBV/B5 coalescence occurred almost 1000 years later. Surprisingly, the HBV/B5 ancestor appears to locate first to Greenland in a rapid coastal route progression based on the landscape aware geographic model, with subsequent B5 evolution and spread westward. Bayesian skyline plot analysis demonstrated an HBV/B5 population expansion occurring approximately 400 YBP, coinciding with the disruption of the Neo-Eskimo Thule culture into more heterogeneous and regionally distinct Inuit populations throughout the North American Arctic.DiscussionHBV/B5 origin and spread appears to occur coincident with the movement of Neo-Eskimo (Inuit) populations within the past 1000 years, further supporting the hypothesis of HBV/host co-expansion, and illustrating the concept of host-pathogen adaptation and balance.
- Published
- 2017
36. Conference Review
- Author
-
Jørgen Hollesen, Julian Bickersteth, Nigel Watson, and Max Friesen
- Subjects
Archeology ,Conservation - Published
- 2014
37. Middle Dorset Communal Structures on Victoria Island
- Author
-
T. Max Friesen
- Subjects
010506 paleontology ,Archeology ,060102 archaeology ,Communal Structure ,Victoria island ,06 humanities and the arts ,Conservation ,Ancient history ,01 natural sciences ,Archaeology ,Education ,Aggregation ,Arctic ,Geography ,Dorset ,geography.geographical_feature ,0601 history and archaeology ,Caribou ,CC1-960 ,0105 earth and related environmental sciences - Abstract
This paper describes a cluster of large communal structures in the Oxford Bay region of southeastern Victoria Island in Nunavut, Arctic Canada. The structures consist of linear stone outlines of up to 24 meters in length, and resemble the relatively well-documented Late Dorset longhouses which have been found across much of the Eastern Arctic. However, radiocarbon dates indicate that the Oxford Bay structures were built and used from roughly 200 to 600-700 cal AD, placing them in the Middle Dorset period. Elsewhere, Middle Dorset communal structures are rare, making the Oxford Bay phenomenon unique. The sites are interpreted as resulting from population aggregations associated with the fall caribou hunt, and may represent direct predecessors of the more widespread Late Dorset longhouses.
- Published
- 2016
38. The Oxford Handbook of the Prehistoric Arctic
- Author
-
T. Max Friesen, Owen K. Mason, T. Max Friesen, and Owen K. Mason
- Subjects
- Excavations (Archaeology)--Arctic regions, Arctic peoples--History, Arctic peoples--Antiquities
- Abstract
The North American Arctic was one of the last regions on Earth to be settled by humans, due to its extreme climate, limited range of resources, and remoteness from populated areas. Despite these factors, it holds a complex and lengthy history relating to Inuit, Iñupiat, Inuvialuit, Yup'ik and Aleut peoples and their ancestors. The artifacts, dwellings, and food remains of these ancient peoples are remarkably well-preserved due to cold temperatures and permafrost, allowing archaeologists to reconstruct their lifeways with great accuracy. Furthermore, the combination of modern Elders'traditional knowledge with the region's high resolution ethnographic record allows past peoples'lives to be reconstructed to a level simply not possible elsewhere. Combined, these factors yield an archaeological record of global significance--the Arctic provides ideal case studies relating to issues as diverse as the impacts of climate change on human societies, the complex process of interaction between indigenous peoples and Europeans, and the dynamic relationships between environment, economy, social organization, and ideology in hunter-gatherer societies. In the The Oxford Handbook of the Prehistoric Arctic, each arctic cultural tradition is described in detail, with up-to-date coverage of recent interpretations of all aspects of their lifeways. Additional chapters cover broad themes applicable to the full range of arctic cultures, such as trade, stone tool technology, ancient DNA research, and the relationship between archaeology and modern arctic communities. The resulting volume, written by the region's leading researchers, contains by far the most comprehensive coverage of arctic archaeology ever assembled.
- Published
- 2016
39. To freeze or to dry: Seasonal variability in caribou processing and storage in the barrenlands of Northern Canada
- Author
-
T. Max Friesen and Andrew M. Stewart
- Subjects
Geography ,Ecology ,Anthropology ,Animal Science and Zoology - Abstract
This paper presents description and interpretation of 20 caribou bone assemblages from Inuit sites on the Kazan River in northern Canada. A diversity of features including caches, disposal areas, and surface scatters, are quantified in order to understand aspects of butchery, transport, and storage of caribou carcasses. Element distributions are compared to four published indices which quantify bone density, food utility, meat drying, and marrow, in order to understand which factors played important roles in decision-making by Inuit in the region. While several factors are identified as having affected these assemblages, by far the most important factor relates to the season during which the caribou were hunted. During warm seasons, the drying of meat dictated relatively complex division of the carcass for processing and storage. During colder seasons, on the other hand, rapid freezing of meat allowed for greater flexibility, which often simply meant that entire articulated carcasses were cached ...
- Published
- 2013
40. Archaeofaunal signatures of specialized bowhead whaling in the Western Canadian Arctic: a regional study
- Author
-
T. Max Friesen and Matthew W. Betts
- Subjects
Taphonomy ,biology ,Ecology ,Archaeological record ,Subsistence economy ,biology.organism_classification ,Prehistory ,Geography ,Arctic ,Anthropology ,Animal Science and Zoology ,Whaling ,Balaena ,Relative species abundance - Abstract
Zooarchaeologists continue to experience difficulty defining the importance of bowhead (Balaena mysticetus) whaling in Neoeskimo coastal deposits. The large size of bowhead bones, combined with their use as structural elements in Neoeskimo architecture, creates a suite of taphonomic issues that tend to obscure their usefulness as a measure of relative abundance, and thus as an overall economic indicator. Here we present a regional approach that focuses on contrasts in relative taxonomic abundance between sites with diverse economic signatures, supported by related differences in element frequencies, site locations, features, artefact frequencies, and manufacturing detritus. Using this approach, a generalized picture of the relative importance of bowhead whales in Neoeskimo subsistence economies can be assembled. Such an analysis, applied to the archaeological record of the Mackenzie Inuit, or Siglit, reveals the role that bowhead whaling played in subsistence economies from the 15 th to 19 th centuries AD. Specifically, the archaeological record indicates that the prehistoric Qikiqtaryungmiut and Nuvugarmiut practiced specialized bowhead whaling at coastal promontories, though the seasonal scheduling and success rate of these hunts contrasted considerably.
- Published
- 2013
41. Pan-Arctic Population Movements
- Author
-
Max Friesen
- Subjects
education.field_of_study ,Geography ,Oceanography ,Pan arctic ,Population ,Climate change ,Physical geography ,education - Abstract
This chapter provides description and interpretation of the two major, well-documented episodes of Arctic-wide migrations. The Paleo-Inuit (also called Paleoeskimo or Arctic Small Tool tradition) migration began around 3,200 B.C., with penetration of the central Arctic by highly mobile, small-scale hunter-gatherer groups. By around 2,500 B.C., the entire eastern Arctic had been peopled by cultures known as Pre-Dorset, Saqqaq, and Independence I. The Thule Inuit migration began around A.D. 1200, when complex maritime-oriented groups from the western Arctic initiated an extremely rapid population movement, spanning the North American Arctic within a generation. The chapter considers the timing and nature of each migration episode, as well as the motivating factors which have been proposed for them, including climate change, social or economic hardship, and acquisition of specific resources such as bowhead whales or metal.
- Published
- 2016
42. Introduction
- Author
-
Owen Mason and Max Friesen
- Abstract
This chapter introduces the central issues relating to the archaeology of the North American Arctic, a region stretching 6,000 km from west to east and 3,000 km south to north. The region is characterized by a uniquely detailed ethnographic record, and excellent preservation of organic remains due to cold temperatures, which together allow particularly high-resolution interpretation of the archaeological record. Themes common to all northern archaeology covered in this chapter include the use of ethnographic analogy to understand ancient archaeological cultures, the role of climate change in archaeological interpretation, the construction of chronologies in an arctic setting, and the role of migration and interaction in the arctic past.
- Published
- 2016
43. Late Dorset
- Author
-
Martin Appelt, Eric Damkjar, and Max Friesen
- Abstract
Late Dorset culture represents the final manifestation of the long-lived Paleoeskimo tradition in the eastern Arctic. Late Dorset occupied an enormous region from Victoria Island to Northern Labrador, and resettled the High Arctic, bringing them to Ellesmere Island and northwest Greenland. Alongside these expansions, long-distance exchange networks were further developed and intensified, perhaps bound together by the aggregation sites located at places with a particular high concentration of seasonally available subsistence resources. Late Dorset aggregation sites are particular visible due to their rows of stone-built hearths and/or “longhouses.” Late Dorset cosmology is visible in several aspects of architecture, as well as through analysis of the more than 1,200 miniature carvings of animals and humans that are known from the period.
- Published
- 2016
44. Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan
- Author
-
Carolyn S. Hudak, Max Friesen, Curtis R. Warren, Fang Xia, and Chad A. Cowan
- Subjects
0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,Aging ,medicine.medical_treatment ,Glucose uptake ,Longevity ,Biophysics ,Adipose tissue ,Adipokine ,030209 endocrinology & metabolism ,White adipose tissue ,Diet, High-Fat ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Insulin resistance ,Adipocyte ,Internal medicine ,medicine ,Adipocytes ,Animals ,Molecular Biology ,Mice, Knockout ,biology ,Insulin ,Cell Biology ,medicine.disease ,Receptor, Insulin ,Insulin receptor ,030104 developmental biology ,Endocrinology ,chemistry ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,biology.protein ,Female ,Insulin Resistance ,Signal Transduction - Abstract
Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan.
- Published
- 2016
45. Dynamic Inuit Social Strategies in Changing Environments: A Long-Term Perspective
- Author
-
T. Max Friesen
- Subjects
History ,Arctic ,Geography, Planning and Development ,Perspective (graphical) ,General Earth and Planetary Sciences ,Climate change ,Ethnology ,Physical geography ,Architecture ,Settlement (litigation) ,Social organization ,Social structure ,Culture change - Abstract
This paper presents an overview of the International Polar Year (IPY) research programme Dynamic Inuit Social Strategies in Changing Environments: A Long-Term Perspective. For this project, research teams from six separate multi-year subprojects performed fieldwork across much of the Canadian Arctic. Fieldwork and analysis revolved around two primary processes critical to the understanding of Inuit history: first, is the migration from Alaska to the east by the earliest Inuit, known as ‘Thule’, an apparently rapid event which replaced populations of the earlier, and culturally very different Dorset tradition; second, is the transformation of Thule Inuit into their more diverse recent cultural forms, involving abandonment of some regions, combined with major changes in settlement patterns, artifact form, architecture, economy, and social organization. The ultimate goal of the project is to understand the variable roles of climate change and social structures on the culture change which can be observed during the past 800 years of Inuit history.
- Published
- 2010
46. Thule Fishing Revisited: The Economic Importance of Fish at the Pembroke and Bell Sites, Victoria Island, Nunavut
- Author
-
T. Max Friesen and Lauren E.Y. Norman
- Subjects
Fishery ,Geography ,Oceanography ,Arctic ,Geography, Planning and Development ,geography.geographical_feature ,Fishing ,Period (geology) ,General Earth and Planetary Sciences ,%22">Fish ,Victoria island ,Zooarchaeology - Abstract
Geografisk Tidsskrift—Danish Journal of Geography 110(2):261–278, 2010 In a comprehensive overview of evidence for fishing in the Thule period of the eastern North American Arctic, Whitridge (2001)...
- Published
- 2010
47. Hearth rows, hierarchies and Arctic hunter-gatherers: the construction of equality in the Late Dorset period
- Author
-
T. Max Friesen
- Subjects
Archeology ,education.field_of_study ,History ,Hearth ,Sedentism ,Archaeological record ,Population ,Archaeology ,Arctic ,Period (geology) ,General Earth and Planetary Sciences ,Social organization ,education ,Hunter-gatherer - Abstract
Around 1000 years ago, the eastern North American Arctic was occupied by people known to archaeologists as Late Dorset, who exhibited a high degree of sedentism, reliance on storage and in some regions a relatively high population density. At the same time, the Late Dorset archaeological record has yielded evidence for a well-developed artistic tradition, construction of elaborate communal structures in many regions and a widespread trade network. This package of traits is often associated with inegalitarian ‘complex hunter-gatherers’, a category represented in its most extreme form by recent First Nations of the Northwest Coast of North America. In the Late Dorset case, however, a number of attributes appear to be more consistent with egalitarian social relations. Most importantly, prominent communal structures in many Late Dorset regions known as ‘longhouses’ and ‘hearth rows’ are best interpreted as overt symbols of equality and homogeneity among Late Dorset individuals and groups. In attempti...
- Published
- 2007
48. Declining foraging returns from an inexhaustible resource? Abundance indices and beluga whaling in the western Canadian Arctic
- Author
-
Matthew W. Betts and T. Max Friesen
- Subjects
Archeology ,History ,biology ,Environmental change ,Whale ,Ecology ,Foraging ,Beluga ,Human Factors and Ergonomics ,biology.organism_classification ,Geography ,Arctic ,biology.animal ,Beluga Whale ,Whaling ,Hunter-gatherer - Abstract
The East Channel of the Mackenzie River supported two of the most populous groups of hunter-gatherers in the Canadian Arctic. These groups, the Kuukpangmiut and Kittegaryumiut, specialized in hunting beluga whales, which aggregate in large numbers in the East Channel during the summer months. Beluga abundance indices (AIs) calculated for a chronological sequence of sites spanning the period ca. 1200–1600 AD indicate that the relative frequencies of beluga whale bones may have fluctuated drastically. A suite of options are considered to explain these indicated shifts in foraging efficiency, including: (1) issues surrounding the calculation of AI values in instances where the encounter rates of less highly ranked taxa are changing; (2) aspects of beluga whale behaviour, demographics, and distribution, including adaptations to environmental change and human predation; and (3) issues relating to the social, demographic, economic, and territorial organization of the Inuit groups occupying the East Channel.
- Published
- 2006
49. Avant-Propos
- Author
-
T. Max Friesen
- Subjects
Anthropology ,Animal Science and Zoology - Published
- 2013
50. Contemporaneity of Dorset and Thule Cultures in the North American Arctic: New Radiocarbon Dates from Victoria Island, Nunavut
- Author
-
T. Max Friesen
- Subjects
Archeology ,geography ,Culture of the United States ,Arctic ,law ,Anthropology ,geography.geographical_feature ,Victoria island ,Radiocarbon dating ,Ancient history ,Archaeology ,law.invention - Published
- 2004
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