The Icefield Ranges Research Project, 1970

In 1970 the Icefield Ranges Research Project (IRRP) conducted its tenth consecutive summer of interdisciplinary basic research in the St. Elias Mountains, Yukon Territory, and in the valley and plateau region to the east where all aspects of the environment reflect the influence of those mountains. Summer field investigations began in April and ended the last week in August. And for the first time since the Project's inception in 1961, two programs have continued through the winter (1970-71). This opportunity to continue studies all the year round was made possible by the winterization of a log house; the work, begun in 1967 on the north side of the runway near the Kluane Base Camp, was completed with modern facilities in June 1970. This short paper briefly reviews the programs which were accomplished during the 1970 field season within the broad categories of glaciology, geophysics, physical geography, biology, and human physiology

The Icefield Ranges Research Project, 1969

The Icefield Ranges Research Project (IRRP) - as was visualized nearly ten years ago - becomes each year more and more a complete study of the environment dominated by the St. Elias Mountains, Canada/Alaska. Since 1967, IRRP has been composed of three closely-integrated research units, planned to achieve the proposed aims of IRRP as defined by Dr. W.A. Wood, the original Project Director, accepted by the Arctic Institute's Board of Governors in 1961, and endorsed by the IRRP Advisory Committee. This report reviews the work accomplished by a total of over 65 scientists, their assistants, and support personnel, during the 1969 summer field season, which opened in mid-May and ended the first week in September. It is composed of post-field summaries by principal investigators researching in the disciplines of glaciology, geophysics, physical geography, botany, zoology, archaeology and physiology

Conceptual structure of the 1996 performance assessment for the Waste Isolation Pilot Plant

The conceptual structure of the 1996 performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP) is described. This structure involves three basic entities (EN1, EN2, EN3): (1) EN1, a probabilistic characterization of the likelihood of different futures occurring at the WIPP site over the next 10,000 yr, (2) EN2, a procedure for estimating the radionuclide releases to the accessible environment associated with each of the possible futures that could occur at the WIPP site over the next 10,000 yr, and (3) EN3, a probabilistic characterization of the uncertainty in the parameters used in the definition of EN1 and EN2. In the formal development of the 1996 WIPP PA, EN1 is characterized by a probability space (S{sub st}, P{sub st}, p{sub st}) for stochastic (i.e., aleatory) uncertainly; EN2 is characterized by a function {line_integral} that corresponds to the models and associated computer programs used to estimate radionuclide releases; and EN3 is characterized by a probability space (S{sub su}, P{sub su}, p{sub su}) for subjective (i.e., epistemic) uncertainty. A high-level overview of the 1996 WIPP PA and references to additional sources of information are given in the context of (S{sub st}, P{sub st}, p{sub st}), {line_integral} and (S{sub su}, P{sub su}, p{sub su})

Modeling complex genetic and environmental influences on comorbid bipolar disorder with tobacco use disorder

Abstract Background Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD. Methods Using meta-analysis, we compared TUD rates for BD patients and the general population. We identified candidate genes showing statistically significant, replicated, evidence of association with both BD and TUD. We assessed commonality among these candidate genes and hypothesized broader, multi-gene network influences on the comorbidity. Using Fisher Exact tests we tested our hypothesized genetic networks for association with the comorbidity, then compared the inferences drawn with those derived from the commonality assessment. Finally, we prioritized candidate SNPs for validation. Results We estimate risk for TUD among BD patients at 2.4 times that of the general population. We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders. We identified a 69 gene network that influences neurotransmitter signaling and shows significant over-representation of genes associated with BD and TUD, as well as genes differentially expressed with exposure to tobacco smoke. Twenty four of these genes are known drug targets. Conclusions This work highlights novel bioinformatics resources and demonstrates the effectiveness of using an integrated bioinformatics approach to improve our understanding of complex disease etiology. We illustrate the development and testing of hypotheses for a comorbidity predisposed by both genetic and environmental influences. Consistent with our hypothesis, the selected network models multiple interacting genetic influences on comorbid BD with TUD, as well as the environmental influence of nicotine. This network nominates candidate genes for validation and drug testing, and we offer a panel of SNPs prioritized for follow-up.http://deepblue.lib.umich.edu/bitstream/2027.42/112449/1/12881_2009_Article_575.pd

Genotype to Phenotype: Diet-By-Mitochondrial DNA Haplotype Interactions Drive Metabolic Flexibility and Organismal Fitness

[Abstract] Diet may be modified seasonally or by biogeographic, demographic or cultural shifts. It can differentially influence mitochondrial bioenergetics, retrograde signalling to the nuclear genome, and anterograde signalling to mitochondria. All these interactions have the potential to alter the frequencies of mtDNA haplotypes (mitotypes) in nature and may impact human health. In a model laboratory system, we fed four diets varying in Protein: Carbohydrate (P:C) ratio (1:2, 1:4, 1:8 and 1:16 P:C) to four homoplasmic Drosophila melanogaster mitotypes (nuclear genome standardised) and assayed their frequency in population cages. When fed a high protein 1:2 P:C diet, the frequency of flies harbouring Alstonville mtDNA increased. In contrast, when fed the high carbohydrate 1:16 P:C food the incidence of flies harbouring Dahomey mtDNA increased. This result, driven by differences in larval development, was generalisable to the replacement of the laboratory diet with fruits having high and low P:C ratios, perturbation of the nuclear genome and changes to the microbiome. Structural modelling and cellular assays suggested a V161L mutation in the ND4 subunit of complex I of Dahomey mtDNA was mildly deleterious, reduced mitochondrial functions, increased oxidative stress and resulted in an increase in larval development time on the 1:2 P:C diet. The 1:16 P:C diet triggered a cascade of changes in both mitotypes. In Dahomey larvae, increased feeding fuelled increased β-oxidation and the partial bypass of the complex I mutation. Conversely, Alstonville larvae upregulated genes involved with oxidative phosphorylation, increased glycogen metabolism and they were more physically active. We hypothesise that the increased physical activity diverted energy from growth and cell division and thereby slowed development. These data further question the use of mtDNA as an assumed neutral marker in evolutionary and population genetic studies. Moreover, if humans respond similarly, we posit that individuals with specific mtDNA variations may differentially metabolise carbohydrates, which has implications for a variety of diseases including cardiovascular disease, obesity, and perhaps Parkinson’s Disease.Supported by Australian Research Grant DP160102575 to JWOB, JC St John, and GKS. National Health and Medical Research Council Fellowship 1058892 and Program Grant 1054618 to GKS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptAustralian Research Council; DP160102575Australia. National Health and Medical Research Council; 1058892Australia. National Health and Medical Research Council; 105461

The Australian dingo is an early offshoot of modern breed dogs

Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo