In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis.
BACKGROUND: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population.
METHODS: Genotype information on 43?641 cancer patients and 370?971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database.
RESULTS: The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele.
CONCLUSIONS: K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.
In the late 18th century explorers and scientists started venturing into the Arctic in a heroic and sometimes deadly effort to understand and unveil the secrets of the unforgiving and mysterious polar region of the high north. Despite that the Arctic was already populated mattered less for the first wave of polar researchers and explorations who nevertheless, brought back valuable knowledge. Today the focus in Arctic science and discourse has changed to one which includes the peoples and societies, and their interaction with the world beyond.
The image of a static Arctic - heralded first by explorers - prevailed for a long time, but today the eyes of the World see the Arctic very differently. Few, if any, other places on Earth are currently experiencing the kind of dramatic change witnessed in the Arctic. According to model forecasts, these changes are likely to have profound implications on biophysical and human systems, and will accelerate in the decades to come.
“The New Arctic” highlights how, and in what parts, the natural and political system is being transformed. We’re talking about a region where demography, culture, and political and economic systems are increasingly diverse, although many common interests and aspects remain; and with the new Arctic now firmly placed in a global context. Settlements range from small, predominantly indigenous communities, to large industrial cities, and all have a link to the surrounding environment, be it glaciers or vegetation or the ocean itself.
“The New Arctic” contributes to our further understanding of the changing Arctic. It offers a range of perspectives, which reflect the deep insight of a variety of scientific scholars across many disciplines bringing a wide range of expertise. The book speaks to a broad audience, including policy-makers, students and scientific colleagues.
Contents: 1 Paths to the New Arctic by Birgitta Evengård, Øyvind Paasche, and Joan Nymand Larsen 2 Indigenous Peoples in the New Arctic by Gail Fondahl, Viktoriya Filippova, and Liza Mack 3 Pioneering Nation: New Narratives About Greenland and Greenlanders Launched Through Arts and Branding by Kirsten Thisted 4 Perpetual Adaption? Challanges for the Sami and Reindeer Husbandry in Sweden by Peter Sköld 5 On Past, Present and Future Arctic Expeditions by Peder Roberts and Lize-Marié van der Watt 6 Arctopias: The Arctic as No Place and New Place in Fiction by Heidi Hansson 7 The Fleeting Glaciers of the Arctic by Øyvind Paasche and Jostein Bakke 8 Arctic Carbon Cycle: Patterns, Impacts and Possible Changes by Are Olsen, Leif G. Anderson, and Christoph Heinze 9 Arctic Vegetation Cover: Patterns, Processes and Expected Change by Bruce C. Forbes 10 Human Development in the New Arctic by Joan Nymand Larsen and Andrey Petrov 11 Issues in Arctic Tourism by Dieter K. Müller 12 The Arctic Economy in a Global Context by Joan Nymand Larsen and Lee Huskey 13 Globalization of the “Arctic” by E. Carina H. Keskitalo and Mark Nuttall 14 Race to Resources in the Arctic: Have We Progressed in Our Understanding of What Takes Place in the Arctic? By Timo Koivurova 15 Comparing the Health of Circumpolar Populations: Patterns, Determinants, and Systems by Kue Young and Susan Chatwood 16 Food Security or Food Sovereignty: What Is the Main Issue in the Arctic? By Lena Maria Nilsson and Birgitta Evengård 17 Water Information and Water Security in the Arctic by Arvid Bring, Jerker Jarsjö, and Georgia Destouni 18 Infectious Disease in the Arctic: A Panorama in Transition by Alan Parkinson, Anders Koch, and Birgitta Evengård 19 Environmental Health in the Changing Arctic by Arja Rautio 20 Scientific Cooperation Throughout the Arctic: The INTERACT Experience by Terry V. Callaghan, Margareta Johansson, Yana Pchelintseva, and Sergey N. Kirpotin 21 The Assessed Arctic: How Monitoring Can Be Silently Normative by Nina Wormbs 22 The Challenge of Governance in the Arctic: Now and in the Future by Douglas C. Nord 23 New Knowledge a Pathway to Responsible Development of the Arctic by Gunnel Gustafsson and Marianne Røgeberg 24 Cryo-History: Narratives of Ice and the Emerging Arctic Humanities by Sverker Sörlin
As a network NordAN advocates the prevention and reducing of alcohol- and drug related harm through effective evidence based alcohol- and drug policy in the Nordic and Baltic countries and in the entire Northern dimension region of Europe.
NordAN was established in September 2000 as a network of non governmental, voluntary organizations who all worked to reduce the consumption of alcohol and other drugs and who supported a restrictive alcohol and drug policy and who did not receive contributions from the commercial alcohol industry.
Acting on these principles NordAN today have grown to have 90 non-governmental, voluntary member organisations in all the eight Nordic and Baltic countries (Denmark, Estonia, Finland, Iceland, Latvia, Lithuania, Norway and Sweden), all active in the alcohol and drug field.
Website includes access to Alcohol News - a weekly newsletter of alcohol news and articles around the world.
Isaaffik is the Greenlandic word for gateway. Isaaffik Arctic Gateway is a user driven web platform supporting research and collaboration. Anyone engaged with Arctic research, education, infrastructure, and logistics may join Isaaffik.
Website includes upcoming events concerning Arctic research, logistics and education.
PEI is a vibrant network promoting polar education and research to a global community. By fostering dialogue and collaboration between educators and researchers, PEI aims to highlight and share the global relevance of the polar regions with the broader community.
The European Polar Board (EPB) is an independent organisation that focuses on major strategic priorities in both the Arctic and Antarctic regions. Current EPB membership includes research institutes, funding agencies, scientific academies, and polar operators from across Europe.
Since 2015, the EPB has been an independent entity, with its Secretariat hosted by the Netherlands Organisation for Scientific Research (NWO). Established in 1995, the EPB was an Expert Board of the European Science Foundation formed to provide strategic advice on Arctic and Antarctic issues.
The EPB has a mission to improve European coordination of Arctic and Antarctic research by optimising the use of European research infrastructure. We promote multilateral collaborations between our Members and provide a single contact point for the global polar research community. We advance the collective knowledge of polar issues, particularly in the context of European societal relevance.
The journal Arctic is North America’s premier journal of northern research. Now in its seventh decade of continuous publication, Arctic is a peer-reviewed, primary research journal that publishes the results of scientific research from all areas of scholarship dealing with the Arctic and subarctic regions. Multidisciplinary in scope, Arctic comprises original scholarly papers in the physical, social, and biological sciences, humanities, and engineering. Also included are book reviews, commentaries, letters to the editor, and profiles of significant people, places, or events of northern interest. The journal is published quarterly and is available through membership in the Arctic Institute of North America.
Cooperation in the Barents Euro-Arctic Region was launched in 1993 on two levels: intergovernmental Barents Euro-Arctic Council (BEAC) and interregional Barents Regional Council (BRC). The overall objective of Barents cooperation has been sustainable development.
The members of the Barents Euro-Arctic Council are Denmark, Finland, Iceland, Norway, Russia, Sweden and the European Commission. The chairmanship of the Barents Euro-Arctic Council rotates between Finland, Norway, Russia and Sweden. Sweden holds the chairmanship for the period 2017-2019.
Fourteen counties or similar sub-national entities form the Barents Regional Council. Finnmark, Norway, is the chair of the BRC for the period 2017-2019.
The two councils have established thematic Working Groups, both independently and jointly. The Working Groups constitute a cross-border platform for exchange for the civil servants and professionals of the respective field. Over the past years, the Working Groups have also implemented several projects.
The representatives of the three indigenous peoples, the Sámi, the Nenets and the Vepsians, cooperate in the Working Group of Indigenous Peoples (WGIP). It has an advisory role in both the BEAC and the BRC which means that their participation is welcome in all Barents Working Groups, that the WGIP Chair is a member of the Committee of Senior Officials (CSO) and the Barents Regional Committee, and that they are always represented at the BEAC Ministerial Sessions and the Barents Regional Council meetings. All three indigenous peoples of the Barents Region can participate individually in the CSO meetings, without a formal invitation.
Available upon request at the Alaska Medical Library, located in UAA/APU Consortium Library. Ask for accession no. 300604.
Contents includes: programme, agenda, The Danish Delegation's notes, talking points, report, the Nuuk Declaration on Environment and Development in the Arctic, accreditation of observers and joint communique.
Work on this bibliography began in 2002. Vera Caine and Angeline Letendre, graduate summer students with the Alberta ACADRE Network, established a database of a r t i - cles p u b - l i s h e d on the topic of ethics in Indigenous health research. In 2003, Caroline Davis, a graduate student with the Alberta ACADRE Network and Travis Jacobs, a summer student at the Kahnawake Schools Diabetes Prevention Program in Quebec, added additional articles. The bibliography is offered in our journal as a resource for anyone interested in the ethical issues related to health research. Vera Caine, Angeline Letendre, and Caroline Davis were funded by the Alberta ACADRE Network. Travis Jacobs received a grant from the Kahnawake Schools Diabetes Prevention Project Centre for Research and Training, and the Aboriginal Mental Health Research Team, McGill University.
Arctic Environment Protection Strategy (AEPS), progress made by the Working Group on Emergency Prevention, Preparedness and Response (EPPR) : report to the Inuvik Ministerial Meeting for the period between the Ministerial Meeting in Nuuk, Greenland, 16 September 1993 and the Ministerial Meeting in Inuvik, Canada, 20-21 March 1996.
Contents: Status report of the Arctic Environment Protection Strategy Working Group on Emergency Prevention, Preparedness and Response for the period between the Ministerial Meeting in Nuuk, Greenland, 16 September 1993 and the Ministerial Meeting in Inuvik, Canada, 20-21 March 1996 -- Arctic Environment Protection Strategy, Anchorage Meeting 28 June-1 July 1994 of the Working Group on Emergency Prevention, Preparedness and Response : chairman's report -- Arctic Environment Protection Strategy, Norilsk Meeting 7-11 August 1995 of the Working Group on Emergency Prevention, Preparedness och [sic] Response : chairman's report -- Arctic Environment Protection Strategy, Open-ended Meeting 27-28 November 1995 in Toronto of the Working Group on Emergency Prevention, Preparedness and Response : chairman's report.
The impacts of global climate change in the Arctic regions : report from a workshop on the impacts of global change, 25-26 April, 1999 The impacts of global climate change in the Arctic regions : report from a workshop on the impacts of global change, 25-26 April, 1999
The enhanced formation of reactive oxygen species (ROS) is a common pathway of toxicity induced by stressful environmental conditions. In polar environments, characterization of antioxidant defences in key sentinel species may be of particular value as early detection biomarkers of unforeseen effects of human activities which are progressively increasing in these remote areas.The complexities associated with predicting the consequences at the 'organism level' of variations of specific antioxidant defences have been recently overcome by the ability to quantify an index of specific biological resistance to various kinds of ROS.The total oxyradical scavenging capacity (TOSC) assay has been used in three species of scallops for quantifying their ability to neutralize peroxyl (ROO(&z.rad;)) and hydroxyl (&z.rad;OH) radicals and peroxynitrite (HOONO). Adamussium colbecki and Chlamys islandicus represent key organisms for monitoring Antarctic and Arctic regions while Pecten jacobaeus was chosen for a comparison with a related temperate species. TOSC values for ROO&z.rad; were significantly higher in A. colbecki indicating this species as the most efficient scavenger of ROO&z.rad;. Mediterranean scallops had the lowest TOSC for ROO(&z.rad;). A. colbecki also exhibited the highest scavenging capacity for &z.rad;OH with values more than 2-fold greater than for C. islandicus and P. jacobaeus. TOSC for HOONO was lower for all scallops as compared to those for ROO&z.rad; or &z.rad;OH. TOSC for microsomes was not significantly different among the species for any ROS studied, and the percentage contribution to the specific TOSC for the various oxidants of microsomes of all scallops accounted for 1-3% of the total TOSC of the post-mitochondrial fraction. The specific TOSC of scallop microsomes for &z.rad;OH was approximately ten times lower than that for ROO&z.rad; or HOONO.The higher basal capability of the Antarctic scallop to neutralize different reactive oxygen species is discussed in terms of a possible adaptation to this extreme environment and TOSC is validated as a quantifiable measure of susceptibility to oxidative stress in marine organisms.
Under the Arctic Research and Policy Act, the US Arctic Research Commission biennially recommends key goals and objectives (“goals report”) for the US Arctic Research Program Plan. To prepare this report, the Commission, through public meetings and by other means, sought substantial input from scientific researchers, policymakers, the public in Alaska and throughout the United States, and the growing number of nations with Arctic interests. The Commission also cosponsored a number of scientific meetings and workshops to help define its research goals and policies, including workshops on oil spill response, impacts of an ice-diminishing Arctic on naval and maritime operations, on the provision of safe supplies of water and sanitary facilities in rural Alaska, on Arctic civil infrastructure, and on “Operating in the Arctic: Supporting US Coast Guard Challenges through Research.”