Cheating on the Edge

We present the results of an individual agent-based model of antibiotic resistance in bacteria. Our model examines antibiotic resistance when two strategies exist: “producers”–who secrete a substance that breaks down antibiotics–and nonproducers (“cheats”) who do not secrete, or carry the machinery associated with secretion. The model allows for populations of up to 10,000, in which bacteria are affected by their nearest neighbors, and we assume cheaters die when there are no producers in their neighborhood. Each of 10,000 slots on our grid (a torus) could be occupied by a producer or a nonproducer, or could (temporarily) be unoccupied. The most surprising and dramatic result we uncovered is that when producers and nonproducers coexist at equilibrium, nonproducers are almost always found on the edges of clusters of producers

Health-related quality of life after vertebral or hip fracture: a seven-year follow-up study

<p>Abstract</p> <p>Background</p> <p>The negative impact of vertebral and hip low-energy fractures on health-related quality-of-life (HRQOL) has been demonstrated previously, but few prospective long-term follow-up studies have been conducted. This study aims to (i) investigate the changes and long-term impact of vertebral or hip fracture and between fracture groups on HRQOL in postmenopausal women prospectively between two and seven years after the inclusion fracture, (ii) compare HRQOL results between fracture and reference groups and (iii) study the relationship between HRQOL and physical performance, spinal deformity index and bone mineral density at seven-year follow-up.</p> <p>Methods</p> <p>Ninety-one women examined two years after a low-energy vertebral or hip fracture were invited to a new examination seven years after the diagnosis. HRQOL was examined using the SF-36 questionnaire and was compared with an age and sex-matched reference group. Physical function was assessed using tests and questionnaires. Bone mineral density was measured. Radiographs of the spine were evaluated using the visual semiquantitative technique. A longitudinal and cross-sectional design was used in this study. Statistical analyses included descriptive statistics, Student's <it>t</it>-tests, ANCOVA, and partial correlation.</p> <p>Results</p> <p>Sixty-seven women participated. In the 42 women (mean age 75.8, SD 4.7) with vertebral fracture as inclusion fracture, bodily pain had deteriorated between two and seven years and might be explained by new fracture. Remaining pronounced reduction of HRQOL was seen in all domains except general health and mental health at seven-year follow-up in women with vertebral fractures compared to the reference group (p < 0.05). All 25 women (mean age 75.0, SD 4.7) with hip fracture as inclusion fracture had no significant changes in HRQOL between two and seven years and did not differ from the reference group regarding HRQOL after seven years. The vertebral group had significantly lower values for bodily pain, vitality, role-emotional function and mental health compared to the hip group. HRQOL showed a positive relationship between physical activity, static balance and handgrip strength.</p> <p>Conclusion</p> <p>The long-term reduction of HRQOL in women with vertebral fracture emerged clearly in this study. The relationships between HRQOL and physical performance in women with vertebral and hip fracture raise questions for more research.</p

Incompatibilities Involving Yeast Mismatch Repair Genes: A Role for Genetic Modifiers and Implications for Disease Penetrance and Variation in Genomic Mutation Rates

Genetic background effects underlie the penetrance of most genetically determined phenotypes, including human diseases. To explore how such effects can modify a mutant phenotype in a genetically tractable system, we examined an incompatibility involving the MLH1 and PMS1 mismatch repair genes using a large population sample of geographically and ecologically diverse Saccharomyces cerevisiae strains. The mismatch repair incompatibility segregates into naturally occurring yeast strains, with no strain bearing the deleterious combination. In assays measuring the mutator phenotype conferred by different combinations of MLH1 and PMS1 from these strains, we observed a mutator phenotype only in combinations predicted to be incompatible. Surprisingly, intragenic modifiers could be mapped that specifically altered the strength of the incompatibility over a 20-fold range. Together, these observations provide a powerful model in which to understand the basis of disease penetrance and how such genetic variation, created through mating, could result in new mutations that could be the raw material of adaptive evolution in yeast populations

Choice-Disability and HIV Infection: A Cross Sectional Study of HIV Status in Botswana, Namibia and Swaziland

Interpersonal power gradients may prevent people implementing HIV prevention decisions. Among 7,464 youth aged 15–29 years in Botswana, Namibia and Swaziland we documented indicators of choice-disability (low education, educational disparity with partner, experience of sexual violence, experience of intimate partner violence (IPV), poverty, partner income disparity, willingness to have sex without a condom despite believing partner at risk of HIV), and risk behaviours like inconsistent use of condoms and multiple partners. In Botswana, Namibia and Swaziland, 22.9, 9.1, and 26.1% women, and 8.3, 2.8, and 9.3% men, were HIV positive. Among both women and men, experience of IPV, IPV interacted with age, and partner income disparity interacted with age were associated with HIV positivity in multivariate analysis. Additional factors were low education (for women) and poverty (for men). Choice disability may be an important driver of the AIDS epidemic. New strategies are needed that favour the choice-disabled

A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females

The Baker's Yeast Diploid Genome Is Remarkably Stable in Vegetative Growth and Meiosis

Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ∼20 vegetative divisions. Similar base substitution rates were estimated for both lines. Given our experimental design, these measures indicated that the meiotic mutation rate is within the range of being equal to zero to being 55-fold higher than the vegetative rate. Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous. A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations to homozygosity as well as for removing mutations. We did not observe 1–2 nt insertion/deletion (in-del) mutations in any of the sequenced lines and only one structural variant in a non-telomeric location was found. However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability. Our results indicate that the diploid yeast nuclear genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious. This work also provides an improved estimate for the mutational load carried by diploid organisms

Phylogenetic and environmental context of a Tournaisian tetrapod fauna

The end-Devonian to mid-Mississippian time interval has long been known for its depauperate palaeontological record, especially for tetrapods. This interval encapsulates the time of increasing terrestriality among tetrapods, but only two Tournaisian localities previously produced tetrapod fossils. Here we describe five new Tournaisian tetrapods ($\textit{Perittodus apsconditus}$, $\textit{Koilops herma}$, $\textit{Ossirarus kierani}$, $\textit{Diploradus austiumensis}$ and $\textit{Aytonerpeton microps}$) from two localities in their environmental context. A phylogenetic analysis retrieved three taxa as stem tetrapods, interspersed among Devonian and Carboniferous forms, and two as stem amphibians, suggesting a deep split among crown tetrapods. We also illustrate new tetrapod specimens from these and additional localities in the Scottish Borders region. The new taxa and specimens suggest that tetrapod diversification was well established by the Tournaisian. Sedimentary evidence indicates that the tetrapod fossils are usually associated with sandy siltstones overlying wetland palaeosols. Tetrapods were probably living on vegetated surfaces that were subsequently flooded. We show that atmospheric oxygen levels were stable across the Devonian/Carboniferous boundary, and did not inhibit the evolution of terrestriality. This wealth of tetrapods from Tournaisian localities highlights the potential for discoveries elsewhere.NERC consortium grants NE/J022713/1 (Cambridge), NE/J020729/1 (Leicester), NE/J021067/1 (BGS), NE/J020621/1 (NMS) and NE/J021091/1 (Southampton

Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis

Introduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF%=-6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.89535) 2 - 0.0067663*(CIT Mean-9.89535) 3, r2=.625, p<.0001. Mean patient survival: 93 % (1 month), 88 % (3 months), 83 % (6 months) and 83 % (12 months). Mean graft survival: 85.9 % (1 month), 80.5 % (3 months), 78.1 % (6 months) and 76.8 % (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ. © 2008 Stahl et al

Forest Plant and Bird Communities in the Lau Group, Fiji

We examined species composition of forest and bird communities in relation to environmental and human disturbance gradients on Lakeba (55.9 km²), Nayau (18.4 km²), and Aiwa Levu (1.2 km²), islands in the Lau Group of Fiji, West Polynesia. The unique avifauna of West Polynesia (Fiji, Tonga, Samoa) has been subjected to prehistoric human-caused extinctions but little was previously known about this topic in the Lau Group. We expected that the degree of human disturbance would be a strong determinant of tree species composition and habitat quality for surviving landbirds, while island area would be unrelated to bird diversity.All trees > 5 cm diameter were measured and identified in 23 forest plots of 500 m² each. We recognized four forest species assemblages differentiated by composition and structure: coastal forest, dominated by widely distributed species, and three forest types with differences related more to disturbance history (stages of secondary succession following clearing or selective logging) than to environmental gradients (elevation, slope, rockiness). Our point counts (73 locations in 1 or 2 seasons) recorded 18 of the 24 species of landbirds that exist on the three islands. The relative abundance and species richness of birds were greatest in the forested habitats least disturbed by people. These differences were due mostly to increased numbers of columbid frugivores and passerine insectivores in forests on Lakeba and Aiwa Levu. Considering only forested habitats, the relative abundance and species richness of birds were greater on the small but completely forested (and uninhabited) island of Aiwa Levu than on the much larger island of Lakeba.Forest disturbance history is more important than island area in structuring both tree and landbird communities on remote Pacific islands. Even very small islands may be suitable for conservation reserves if they are protected from human disturbance

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility