Summary Adaptive evolution plays a large role in generating the phenotypic diversity observed in nature, yet current methods are impractical for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. Here we used a DNA barcoding approach to generate the genotype-to-fitness map for adaptation-driving mutations from a Saccharomyces cerevisiae population experimentally evolved by serial transfer under limiting glucose. We isolated and measured the fitness of thousands of independent adaptive clones, and sequenced the genomes of hundreds of clones. We found only two major classes of adaptive mutations: self-diploidization, and mutations in the nutrient-responsive Ras/PKA and TOR/Sch9 pathways. Our large sample size and precision of measurement allowed us to determine that there are significant differences in fitness between mutations in different genes, between different paralogs, and even between different classes of mutations within the same gene.

Major national and international critiques of the medical curriculum in the 1980s noted the following significant flaws: (1) over-reliance on learning by rote memory, (2) insufficient exercise in analysis and synthesis/conceptualization, and (3) failure to connect the basic and clinical aspects of training. It was argued that the invention of computers and related imaging techniques called to question the traditional instruction based on the faculty-centered didactic lecture. In the ensuing reform, which adopted case-based, small group, problem-based learning, time allotted to anatomical instruction was severely truncated. Many programs replaced dissection with prosections and computer-based learning. We argue that cadaver dissection is still necessary for (1) establishing the primacy of the patient, (2) apprehension of the multidimensional body, (3) touch-mediated perception of the cadaver/patient, (4) anatomical variability, (5) learning the basic language of medicine, (6) competence in diagnostic imaging, (7) cadaver/patient-centered computer-assisted learning, (8) peer group learning, (9) training for the medical specialties. Cadaver-based anatomical education is a prerequisite of optimal training for the use of biomedical informatics. When connected to dissection, medical informatics can expedite and enhance preparation for a patient-based medical profession. Actual dissection is equally necessary for acquisition of scientific skills and for a communicative, moral, ethical, and humanistic approach to patient care. Anat Rec (New Anat) 269:20-32, 2002.

Previous meta-analyses have shown that the anti-diabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiological studies. We performed a meta-analysis with a focus on confounders and biases, including BMI, study type, and time related biases. We identified 71 articles published between January 1, 1966 to May 31, 2013 through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and the Cochrane library that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. We included estimates from 47 independent studies and 65,540 cancer cases in diabetic patients. Overall cancer incidence was reduced by 31% (SRR=0.69, 95%CI: 0.52–0.90), although between-study heterogeneity was considerable (I2=88%). Cancer mortality was reduced by 34% (SRR=0.66, 95%CI: 0.54–0.81; I2=21%). BMI-adjusted studies and studies without time-related biases also showed significant reduction in cancer incidence (SRR=0.82, 95%CI: 0.70–0.96 with I2=76% and SRR=0.90; 95%CI: 0.89–0.91 with I2=56%, respectively), albeit with lesser magnitude (18% and 10% reduction, respectively). However, studies of cancer mortality and individual organ sites did not consistently show significant reductions across all types of analyses. Although these associations may not be causal, our results show that metformin may reduce cancer incidence and mortality in diabetic patients. However the reduction seems to be of modest magnitude and not affecting all populations equally. Clinical trials are needed to determine if these observations apply to non-diabetic populations and to specific organ sites.

Although the budding yeast Saccharomyces cerevisiae is arguably one of the most well-studied organisms on earth, the genome-wide variation within this species—i.e., its “pan-genome”—has been less explored. We created a multispecies microarray platform containing probes covering the genomes of several Saccharomyces species: S. cerevisiae, including regions not found in the standard laboratory S288c strain, as well as the mitochondrial and 2-μm circle genomes–plus S. paradoxus, S. mikatae, S. kudriavzevii, S. uvarum, S. kluyveri, and S. castellii. We performed array-Comparative Genomic Hybridization (aCGH) on 83 different S. cerevisiae strains collected across a wide range of habitats; of these, 69 were commercial wine strains, while the remaining 14 were from a diverse set of other industrial and natural environments. We observed interspecific hybridization events, introgression events, and pervasive copy number variation (CNV) in all but a few of the strains. These CNVs were distributed throughout the strains such that they did not produce any clear phylogeny, suggesting extensive mating in both industrial and wild strains. To validate our results and to determine whether apparently similar introgressions and CNVs were identical by descent or recurrent, we also performed whole-genome sequencing on nine of these strains. These data may help pinpoint genomic regions involved in adaptation to different industrial milieus, as well as shed light on the course of domestication of S. cerevisiae.

Background: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseedsupplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and