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America's globally preeminent university research enterprise is constructed on two bedrock principles of self-governance. The first is autonomy: academic scientists should be left free to determine their own research agendas. The second is internal accountability: the quality of academic science is best assessed by academic scientists. The commitment to scientific self-governance carries with it a policy requirement as well: support for research will mostly have to come from the federal government; companies will never make the necessary investments in undirected research because they cannot capture the economic benefits for themselves.The origin story of how this arrangement came about is a familiar one. During World War II, civilian scientists and engineers developed pivotal innovations that contributed to the allied victory. Their work was funded, overseen, and coordinated by the US Office of Scientific Research and Development, directed by Vannevar Bush, formerly the president of the Carnegie Institution for Science and dean of engineering at the Massachusetts Institute of Technology. Closely administered for relevance in advancing the war effort, wartime research and development activities were managed in a manner antithetical to contemporary ideals of scientific selfgovernance. Following the war, Bush made a pitch in his now famous report Science, The Endless Frontier that to secure social and economic benefits in the postwar period, including more and better paying jobs, more productive agriculture, and innovative industrial products desired by consumers, \"the flow of scientific knowledge must be both continuous and substantial.\" To achieve this knowledge flow he felt that the government should provide generous funding for the scientific community, as it had during the war.

Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.

Coat color and type are essential characteristics of domestic dog breeds. Although the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5, and keratin-71, respectively), that together account for most coat phenotypes in purebred dogs in the United States. Thus, an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.

The size, shape, and behavior of the modern domesticated dog has been sculpted by artificial selection for at least 14,000 years. The genetic substrates of selective breeding, however, remain largely unknown. Here, we describe a genome-wide scan for selection in 275 dogs from 10 phenotypically diverse breeds that were genotyped for over 21,000 autosomal SNPs. We identified 155 genomic regions that possess strong signatures of recent selection and contain candidate genes for phenotypes that vary most conspicuously among breeds, including size, coat color and texture, behavior, skeletal morphology, and physiology. In addition, we demonstrate a significant association between HAS2 and skin wrinkling in the Shar-Pei, and provide evidence that regulatory evolution has played a prominent role in the phenotypic diversification of modern dog breeds. Our results provide a first-generation map of selection in the dog, illustrate how such maps can rapidly inform the genetic basis of canine phenotypic variation, and provide a framework for delineating the mechanistic basis of how artificial selection promotes rapid and pronounced phenotypic evolution.

Information we collect about our planet depends, in part, on the questions scientists ask regarding the natural world. Asking other questions might lead to different innovations and alternative understandings of policy problems and their potential solutions. With a seemingly infinite number of potential study subjects but limited resources with which to study them, why have we chosen to focus on the topics that we have? Here, I present a Q-method study that explores ecologists' thought processes as they evaluate the merits of potential research topics. The participants, ecologists attending the Ecological Society of America's 2008 Annual Meeting, nominally agreed with one another that their discipline should contribute to solving environmental problems, but they interpreted that goal differently. This study uncovers four competing visions that ecologists have for their discipline. On the basis of these findings, I contend that ecology might be more effective in informing policy if priority setting were a more deliberative process and open to insights from individuals and institutions outside of ecology.

A crippling dwarfism was first described in the Miniature Poodle in Great Britain in 1956. Here, we resolve the genetic basis of this recessively inherited disorder. A case-control analysis (8:8) of genotype data from 173 k SNPs revealed a single associated locus on CFA14 (P(raw) <10(-8)). All affected dogs were homozygous for an ancestral haplotype consistent with a founder effect and an identical-by-descent mutation. Systematic failure of nine, nearly contiguous SNPs, was observed solely in affected dogs, suggesting a deletion was the causal mutation. A 130-kb deletion was confirmed both by fluorescence in situ hybridization (FISH) analysis and by cloning the physical breakpoints. The mutation was perfectly associated in all cases and obligate heterozygotes. The deletion ablated all but the first exon of SLC13A1, a sodium/sulfate symporter responsible for regulating serum levels of inorganic sulfate. Our results corroborate earlier findings from an Slc13a1 mouse knockout, which resulted in hyposulfatemia and syndromic defects. Interestingly, the metabolic disorder in Miniature Poodles appears to share more clinical signs with a spectrum of human disorders caused by SLC26A2 than with the mouse Slc13a1 model. SLC26A2 is the primary sodium-independent sulfate transporter in cartilage and bone and is important for the sulfation of proteoglycans such as aggregan. We propose that disruption of SLC13A1 in the dog similarly causes undersulfation of proteoglycans in the extracellular matrix (ECM), which impacts the conversion of cartilage to bone. A co-dominant DNA test of the deletion was developed to enable breeders to avoid producing affected dogs and to selectively eliminate the mutation from the gene pool.

Recent political events serve as a reminder that American society comprises groups with divergent visions for the future and mutually incompatible ideas of how to achieve those futures. Despite this diversity of policy orientations within the American public, we find that many students in our environmental studies courses have relatively little awareness of, or experience with, that diversity. Without the experience of interacting with people with different policy orientations, it is easy for students to believe policy consensus would emerge if everyone were sufficiently educated on the facts. Factual understanding, however, does not yield consensus on contemporary policy dilemmas such as climate change. We believe that equipping students to be effective agents of change means exposing them to the plurality of cultural commitments and policy orientations latent in current policy disputes. In this paper, we present a preliminary version of a survey tool, the Policy Orientation Survey, to evaluate how the diversity of cultural and policy orientations at a university is distributed across academic units. After describing the tool and its utility, we briefly present pilot results from our own university and discuss implications for higher education.

We have leveraged the reference sequence of a boxer to construct the first complete linkage map for the domestic dog. The new map improves access to the dog's unique biology, from human disease counterparts to fascinating evolutionary adaptations. The map was constructed with ∼3000 microsatellite markers developed from the reference sequence. Familial resources afforded 450 mostly phase-known meioses for map assembly. The genotype data supported a framework map with ∼1500 loci. An additional ∼1500 markers served as map validators, contributing modestly to estimates of recombination rate but supporting the framework content. Data from ∼22,000 SNPs informing on a subset of meioses supported map integrity. The sex-averaged map extended 21 M and revealed marked region- and sex-specific differences in recombination rate. The map will enable empiric coverage estimates and multipoint linkage analysis. Knowledge of the variation in recombination rate will also inform on genomewide patterns of linkage disequilibrium (LD), and thus benefit association, selective sweep, and phylogenetic mapping approaches. The computational and wet-bench strategies can be applied to the reference genome of any nonmodel organism to assemble a de novo linkage map.