John Bell (1796-1868)

John Bell, discoverer of the Yukon River and associate of Drs. John Richardson and John Rae in the Franklin search expedition of 1847-1849, represented the classic blend of fur trader and explorer. His contributions to the expansion of the Company's trade in the far northwest and to the cause of arctic exploration have gone largely unnoticed, due in some measure to his unassuming and modest character. ... His northern career began in 1824 when, as an officer of the reorganized Hudson's Bay Company, he was transferred to the Mackenzie District. In 1837, Thomas Simpson and Peter Warren Dease had discovered the Colville River on the arctic coast. Anxious to exploit this find, Governor Simpson ordered that John Bell, by now an experienced northern trader, attempt to locate an overland route joining the Mackenzie and the Colville. In 1839, Bell travelled along the lower reaches of the Peel River, looking for a breach in the mountains that would take him west. Though he did not immediately succeed, his reports of the excellent prospects for trade encouraged the Company to establish a trading post. Bell opened Peel's River Post, later renamed Fort McPherson, in 1840. On Governor Simpson's directions, he also continued his explorations of the lands west of the Mackenzie. ... The Hudson's Bay Company took an active part in the attempt to locate the lost Franklin expedition. In 1847, Governor Simpson assigned John Bell to assist with an expedition, led by Drs. John Richardson and John Rae, that searched the coast between the Mackenzie and Coppermine rivers. Bell's primary responsibility was to provide logistic support for the venture; during 1848, for example, Bell built Fort Confidence on Great Bear Lake as a wintering station for the expedition. At the completion of Richardson and Rae's journey, Bell returned to his fur trade duties and was assigned to Fort Liard. ... Many northern explorers rushed descriptions of their travels into print, anxious to share news of their discoveries and to bask in the fame due a northern explorer. Bell did not, offering lengthy accounts in his letters to HBC officers, but making little effort to spread his story further. He tackled these duties without the enthusiasm and sense of destiny that inspired other HBC explorers. He was, in fact, a fur trader rather than an explorer, both in talent and temperament. Throughout his northern career, he placed primary importance on the organization and management of the trading posts he commanded, and although he accepted the exploration assignments with few complaints, he preferred the life of a fur trader. ..

Father J.M. Mouchet

"Motivation!" That single word, spoken with a strong French accent and remarkable conviction, resonates in the ears of hundreds of northern Canadian cross-country skiers, past and present. The speaker, Father J.M. Mouchet, O.M.E., played an instrumental role in introducing the sport to the North in the 1960s. His remarkable dedication and enthusiasm for cross-country skiing - for the North, and for the Native people - has left a mark on the entire region. ... Always an active sportsman, Mouchet was very impressed with the Natives' physical fitness, which he attributed to their active lifestyle and adaptation to their environment. He further believed that the Natives faced tremendous social and economic changes as a result of th expansion of non-Native society in the North. Physical achievement through cross-country skiing, he believed, offered Native children the self-esteem and the physical and mental toughness to deal with rapidly changing times. Mouchet put these ideas into action. He organized cross-country skiing teams in Old Crow and, with the assistance of others who shared his vision, in Inuvik. The Native participants in the Territorial Experimental Ski Training (TEST) Programme proved the correctness of his vision. A number of the skiers that he brought into the sport became members of Canada's national ski team; the Firth sisters, Sharon and Shirley, are examples. Native skiers dominated skiing competitions throughout the North for a number of years. ... Mouchet moved his training scheme to Whitehorse, where it was introduced into the elementary school system. From modest beginnings - with seven pairs of skis at Takhini Elementary - the cross-country ski training program became one of the most popular participation sports in the territory. ... Father Mouchet now resides in Whitehorse. He continues to be active in cross-country skiing, showing the same dedication and encouragement that he first brought to the Canadian North over forty years ago. ..

Increasing the availability and utilization of reliable data on population micronutrient (MN) status globally: the MN Data Generation Initiative.

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support

Formation of the Isthmus of Panama

The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed manymillions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways,withformationof theIsthmus of Panama sensustricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.Facultad de Ciencias Naturales y Muse

Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer

BACKGROUND: Although the nuclear factor-erythroid 2-related factor 2 (NRF2) pathway is one of the most frequently dysregulated in cancer, it is not clear whether mutational status is a good predictor of NRF2 activity. Here we utilise four members of the aldo-keto reductase (AKR) superfamily as biomarkers to address this question. METHODS: Twenty-three cell lines of diverse origin and NRF2-pathway mutational status were used to determine the relationship between AKR expression and NRF2 activity. AKR expression was evaluated in lung cancer biopsies and Cancer Genome Atlas (TCGA) and Oncomine data sets. RESULTS: AKRs were expressed at a high basal level in cell lines carrying mutations in the NRF2 pathway. In non-mutant cell lines, co-ordinate induction of AKRs was consistently observed following activation of NRF2. Immunohistochemical analysis of lung tumour biopsies and interrogation of TCGA data revealed that AKRs are enriched in both squamous cell carcinomas (SCCs) and adenocarcinomas that contain somatic alterations in the NRF2 pathway but, in the case of SCC, AKRs were also enriched in most other tumours. CONCLUSIONS: An AKR biomarker panel can be used to determine NRF2 status in tumours. Hyperactivation of the NRF2 pathway is far more prevalent in lung SCC than previously predicted by genomic analyses

The Scientific Foundation for Personal Genomics: Recommendations from a National Institutes of Health–Centers for Disease Control and Prevention Multidisciplinary Workshop

The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead