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Cell competition is emerging as a quality control mechanism that eliminates unfit cells in a wide range of settings from development to the adult. However, the nature of the cells normally eliminated by cell competition and what triggers their elimination remains poorly understood. Here we have performed single cell transcriptional profiling of early mouse embryos and find that the cells eliminated show the hallmarks of cell competition, are mis-patterned and have mitochondrial defects. We demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function is sufficient to trigger competition. Importantly, we show that in the embryo loser epiblast cells display mitochondrial DNA mutations and that even small changes in mitochondrial DNA sequence can influence the competitive ability of the cell. Our results therefore suggest that cell competition is a purifying selection that optimises metabolic output prior to gastrulation.

Cell competition is a quality control mechanism that eliminates cells which are viable but less fit than surrounding cells. The outcome of cell competition is enhanced organismal fitness as the process prevents the propagation of cells which are oncogenic, mispatterned, or otherwise sub-optimal. Cell competition research has largely been performed in flies, although recently it was found that cells in the early mammalian embryo are sensitive to competitive interactions. However, the underlying mechanisms driving the elimination of less fit cells in this system remain largely unknown. Here, we interrogate competition mechanisms in the early mammalian embryo. First, we postulate that senescence may have a role in mediating the out-competition of defective cells. While our evidence does not provide support for this framework, we observed an upregulation of senescence-associated phenotypes in the early post-implantation epiblast. Second, we find that the confrontation of cells with different fitness levels leads to a repression of mTOR signalling in the less-fit cell type. This repression is sufficient to trigger apoptosis, and hyperactivation of the mTOR pathway rescues loser cell elimination and allows less-fit tetraploid cells to contribute to later developmental stages. Finally, we find that less-fit cell types are marked by elevated levels of p53, and loss of p53 prevents both loser cell elimination and mTOR pathway repression. Furthermore, mutations affecting p53/mTOR activity increase the competitive ability of cells within the embryo and cause tissue overgrowths that prevent proper morphogenesis and patterning. Our results shed light on the mechanisms of cell competition in development but also allude to a role for cell competition in the elimination of damaged or nutrient-stressed cells prior to gastrulation. Open Access

The primary objectives of this study were to determine patterns of traffic flow and develop traffic growth rates by traffic composition and highway type for Kentucky’s system of highways. Additional subtasks included the following: 1) a literature search to determine if there were new procedures being used to more accurately represent traffic growth rates, 2) development of a random sampling procedure for collecting traffic count data on local roads and streets, 3) prediction of vehicle miles traveled based on socioeconomic data, 4) development of a procedure for explaining the relationship and magnitude of traffic volumes on routes functionally classified as collectors and locals, and 5) development of county-level growth rates based on procedures to estimate or model trends in vehicle miles traveled and average daily traffic. Results produced a random sampling procedure for traffic counting on local roads which were used as part of the effort to model traffic growth at the county level in Kentucky. Promising results were produced to minimize the level of effort required to estimate traffic volumes on local roads by development of a relationship between functionally classified collector roads and local roads. Both regression and logarithmic equations were also developed to explain the relationship between local and collector roads. County-level growth rates in traffic volumes were analyzed and linear regression was used to represent changes in ADT to produce county-level growth rates by functional class. Linear regression and Neural Networks models were developed in an effort to estimate interstate and non-interstate vehicle miles traveled.

This report summarizes the results of a phone survey which evaluated the user satisfaction of the telephone traveler information service, ARTIMIS, in Cincinnati/Northern Kentucky. Information was also gathered on the users preference for a 3 versus 7 digit access number, use patterns, and user characteristics. The sample was obtained by intercepting calls to the service during Winter 1999. Users rated the service high. Common suggestions for improvements included longer hours of operation and coverage of more roads suggesting the service is valuable to its users. The travelers perceived that they benefited most by avoiding traffic problems, saving time, and reducing frustration. Of the 65% that would be willing to pay for the service, $0.25 was the average maximum payment they would be willing to make. The respondents had been using the service for an average of 13 months and made on average 4.3 calls per week. The 3 digit number, 211, was the most commonly used and recognized access number. Approximately 80 percent of individuals felt they would personally benefit from a nation-wide 3-digit number for travel information. Landline 211 calls result in an extra cost to operators of the system. Although these callers make less frequent calls, they are also more likely to make route or trip changes resulting in a public overall system benefit.

Fifty-one male coal miners between 18 and 65 years old (78% underground and 22% surface miners) completed a self-administered questionnaire. Population and food pattern characteristics were described. Food frequencies were used to obtain a food score which was a weighted average of the frequency of use each month for each food item as determined by the characteristics. Cluster analysis on the food scores were used to identify foods as core, secondary or peripheral foods. Core foods were foods consumed at least ten times in a 28 day period. The food frequencies were used to calculate an estimated daily dietary score for nine nutrients. These scores were compared with the U.S. Dietary Guidelines. Thirty-two percent of the miners had worked in the mines longer than 15 years, 80% had a family history of coal mining, 50% were between the ages of 18 and 35, 52% worked the eight a.m. to four p.m. shift, and 63% had an 11-12 grade education. Eating three times a day was the most frequent eating pattern. When food choices during non-work times were compared to choices when working, the kind and amount of food differed. Time of meals also differed. Analyses of variance indicated that the food scores were significantly different at the .05 level for the type of mining and for income levels; foods scores for education levels, work hours and age characteristics were significantly different at the 0.1 level. As a group, the miners had a high fat, sodium and protein intake, a medium total carbohydrate intake with a low fiber intake. In order for the miners to meet the U.S. Dietary Guidelines, nutrition educators may need to focus educational programs on the guidelines emphasizing a dietary increase in starch and fiber, a decrease in refined carbohydrate, a decrease in total fat, cholesterol, saturated fat and sodium. Master of Science