Separating the effects of mutation and selection in producing DNA skew in bacterial chromosomes

<p>Abstract</p> <p>Background</p> <p>Many bacterial chromosomes display nucleotide asymmetry, or skew, between the leading and lagging strands of replication. Mutational differences between these strands result in an overall pattern of skew that is centered about the origin of replication. Such a pattern could also arise from selection coupled with a bias for genes coded on the leading strand. The relative contributions of selection and mutation in producing compositional skew are largely unknown.</p> <p>Results</p> <p>We describe a model to quantify the contribution of mutational differences between the leading and lagging strands in producing replication-induced skew. When the origin and terminus of replication are known, the model can be used to estimate the relative accumulation of G over C and of A over T on the leading strand due to replication effects in a chromosome with bidirectional replication arms. The model may also be implemented in a maximum likelihood framework to estimate the locations of origin and terminus. We find that our estimations for the origin and terminus agree very well with the location of genes that are thought to be associated with the replication origin. This indicates that our model provides an accurate, objective method of determining the replication arms and also provides support for the hypothesis that these genes represent an ancestral cluster of origin-associated genes.</p> <p>Conclusion</p> <p>The model has several advantages over other methods of analyzing genome skew. First, it quantifies the role of mutation in generating skew so that its effect on composition, for example codon bias, can be assessed. Second, it provides an objective method for locating origin and terminus, one that is based on chromosome-wide accumulation of leading <it>vs </it>lagging strand nucleotide differences. Finally, the model has the potential to be utilized in a maximum likelihood framework in order to analyze the effect of chromosome rearrangements on nucleotide composition.</p

Nomenclatural validation of two extant Congeria species, C. jalzici and C. mulaomerovici (Bivalvia: Dreissenidae) from the caves of the Dinaric karst

Two extant cave-dwelling bivalves of the dreissenid genus Congeria were recently described by Morton et Bilandžija in Bilandžija et al. (2013) as Congeria jalzici Morton et Bilandžija and C. mulaomerovici Morton et Bilandžija. Unfortunately, the volume of the Frontiers in Zoology in which the descriptions were published was online-only and did not include a Zoobank registration number (LSID), which is required for validation of new names in electronic-only publications (ICZN, 2012). In consequence, the names C. jalzici and C. mulaomerovici should not be available according to the International Code of Zoological Nomenclature (ICZN 1999, 2012). Therefore, the present note serves to validate the names C. jalzici and C. mulaomerovici by fulfilling the ICZN conditions for nomenclatural availability. The holotypes of both species are deposited in the General Collection of Recent Molluscs, Croatian Natural History Museum, Zagreb and in The National Museum of Bosnia and Herzegovina, Sarajevo. Accordingly, the date and authorship of the new species names are those of this note and not those of Bilandžija et al. (2013)

The Chesapeake Bay and the Control of NOx Emissions: A Policy Analysis

Nitrogen oxide emissions not only affect air quality but have recently been found to be an important source of nitrate pollution in the Chesapeake Bay. This analysis examines the costs, emissions, source-specific and location-specific allocations of NOX emissions reductions and the ancillary ozone related health benefits under a range of policy scenarios. The paper includes analysis of three separate policies. The first is a detailed analysis of the effect on nitrate loadings to the Bay of command and control policies specified in the Clean Air Act and as part of the OTAG process. The second is a comparison of alternative scenarios for reducing NOX emissions that meet nitrate loading goals, with or without concern for reducing ozone concentrations and the health effects they cause. The third is a comparison of alternative approaches to allocate NOX emissions to meet NOX reduction and ozone exposure goals while capturing the ancillary effect on nitrate loadings. This last analysis focuses on the stake the Bay jurisdictions have in the outcome of negotiations over NOX trading programs being developed by EPA for reducing ozone in the Eastern U.S. With the primary focus on the Chesapeake Bay jurisdiction, all three analyses integrate the ancillary ozone benefits of policies to reduce nitrate pollution, including examination of how these ancillary benefits change under alternative meteorological episodes, and explore lower cost alternatives to current regulatory programs in both qualitative and quantitative terms. We find that the Chesapeake Bay benefits from efforts to reduce NOX emissions to meet the ambient air quality standard for ozone. Airborne NOX emission reductions slated to occur under the Clean Air Act in the Bay airshed will reduce nitrate loadings to the Bay by about 27 percent of the baseline airborne levels. The additional controls of NOX contemplated in what we term the OTAG scenario is estimated to result in an additional 20 percent reduction from this baseline. However, the paper's analysis of possible least cost options shows that the costs of obtaining such reductions can be significantly reduced by rearranging the allocation of emissions reductions to take advantage of source-type and locational considerations. In addition, we find that adding consideration of ancillary ozone-related health benefits to the picture does not alter any qualitative conclusions. Quantitatively, unless a link between ozone and mortality risk is assumed, the benefits are too small to affect the cost-saving allocations of NOX reductions. If the case for such a link can be made, the results change dramatically, with large overall increases in NOX reductions and a relative shift in controls to non-Bay states and utility sources. These specific effects are sensitive to the source-receptor coefficients linking NOX to ozone, however. Our analyses also suggest that the Bay jurisdictions have a stake in the outcome of the NOX trading debate -- that some trading designs can lead to better outcomes for these jurisdictions than others. Nevertheless, a common feature of cost-savings policies is that they both rearrange emissions reductions and, in the aggregate, reduce emissions less than a command and control system. Thus, some trading regimes result in significantly smaller loadings reductions (up to 25 percent smaller) than the command and control approach.

Shh signaling and pancreatic cancer: implications for therapy

Hedgehog signaling has been implicated in the development of several human cancers, including small cell lung carcinomas, medulloblastomas, basal cell carcinomas, and digestive tract tumors. Elevated levels of pathway components are observed in pancreatic ductal adenocarcinoma (PDAC) precursor lesions, and these levels increase further as lesions progress to more advanced stages. Yet the mechanisms by which hedgehog signaling contributes to pancreatic tumorigenesis were poorly understood. We recently published results showing that activated hedgehog signaling enhances the proliferation and survival of pancreatic duct epithelial cells, the presumptive target cells for PDAC development. We also demonstrated that sonic hedgehog (Shh) expression, in cooperation with loss of the Trp53 and Ink4a/Arf tumor suppressor loci, was sufficient to initiate the formation of early pancreatic lesions. Furthermore, Shh signaling enhanced K-Ras-mediated pancreatic tumorigenesis and reduced the dependence of tumor cells on the sustained activation of Ras-stimulated signaling pathways. Here we discuss the significance of these findings and the implications for therapy

Temporal Changes in the Macroinvertebrate Fauna of Two Glacial Lakes, Cootapatamba and Albina, Snowy Mountains, New South Wales

Before 2003, unique assemblages of aquatic invertebrates in Lake Cootapatamba and Lake Albina lived in a fishless environment. A sequence of events in 2003 following a large-scale bushfire in the area allowed the native Mountain Galaxias Galaxias olidus to enter Lake Cootapatamba. This study determines the extent of any temporal changes in the invertebrate assemblages of each lake and whether the introduction of fish into Lake Cootapatamba affected these assemblages. The littoral and benthic fauna of both lakes were found to have changed since the earliest studies of these lakes in 1997/1998 and 1976, respectively. In particular, there has been a large decrease in the abundance of the isopod Metaphreatoicus australis and planarians, and the gastropod Glacidorbis hedleyi and amphipod Neoniphargus sp. have apparently disappeared. The effect is greatest in the benthos and in Lake Cootapatamba, so while fish seemed to have affected some invertebrates in some habitats, other factors may be acting. Sometime since 1976, the exotic worm Lumbriculus variegatus arrived into Lake Albina. Shifts in the representation of other taxa, such as ephemeropterans, plecopterans, tricopterans, dipterans and coleopterans, are thought to reflect natural year-to-year fluctuations but more data are needed

Temporal Changes in the Macroinvertebrate Fauna of Two Glacial Lakes, Cootapatamba and Albina, Snowy Mountains, New South Wales

Before 2003, unique assemblages of aquatic invertebrates in Lake Cootapatamba and Lake Albina lived in a fishless environment. A sequence of events in 2003 following a large-scale bushfire in the area allowed the native Mountain Galaxias Galaxias olidus to enter Lake Cootapatamba. This study determines the extent of any temporal changes in the invertebrate assemblages of each lake and whether the introduction of fish into Lake Cootapatamba affected these assemblages. The littoral and benthic fauna of both lakes were found to have changed since the earliest studies of these lakes in 1997/1998 and 1976, respectively. In particular, there has been a large decrease in the abundance of the isopod Metaphreatoicus australis and planarians, and the gastropod Glacidorbis hedleyi and amphipod Neoniphargus sp. have apparently disappeared. The effect is greatest in the benthos and in Lake Cootapatamba, so while fish seemed to have affected some invertebrates in some habitats, other factors may be acting. Sometime since 1976, the exotic worm Lumbriculus variegatus arrived into Lake Albina. Shifts in the representation of other taxa, such as ephemeropterans, plecopterans, tricopterans, dipterans and coleopterans, are thought to reflect natural year-to-year fluctuations but more data are needed

Formulating LUTI Calibration As an Optimisation Problem: Estimation of Tranus Shadow Price and Substitution Parameters

International audienceCities and their employment catchment areas are focus points of economic activity, transportation, and social interactions. The need for land use and transport integrated modelling (LUTI modelling) as a decision aid tool in urban planning, has become apparent. Instantiating such models on cities, requires a substantial data collection, model structuring and parameter estimation effort; for conciseness, the latter is referred to here as calibration. This work is a partial effort towards the integrated calibration of LUTI models. It considers one of the most widely used LUTI models and softwares, Tranus. The usual calibration approach for Tranus is briefly reviewed. It is then reformulated as an optimisa-tion problem, in order to make it amenable to the systematic incorporation of constraints on parameters and additional data and to form a clear basis for future fully integrated calibration. The problem at hand concerns a dynamic system; an approach is shown how to " eliminate " parts of the dynamics in order to ease the parameter optimisation. We also discuss how to validate calibration results and propose to use synthetic data generated from real world problems in order to assess convergence properties and accuracy of calibration methods

Contributions to the calibration of integrated land use and transportation models

International audienceThe need for land use and transport integrated modelling (LUTI modelling) as a decision aid tool in urban planning, has become apparent. Instantiating such models on cities, requires a substantial data collection, model structur-ing and parameter estimation effort. This work is a partial effort towards the integrated calibration of LUTI models. It considers one of the most widely used LUTI models and softwares, Tranus. The usual calibration approach for Tranus is briefly reviewed, then the calibration of Tranus' land use module is reformulated as an optimisation problem, proposing a clear basis for future fully integrated calibration. We analyse the case of transportable and non-transportable economic sectors. We also discuss how to validate calibration results and propose to use synthetic data generated from real world problems in order to assess convergence properties and accuracy of calibration methods. Finally, results of this methodology are presented for real world scenarios

Mitigation of Global Navigation Satellite System Cycle Slips Due to Scintillation Using Radio Backpropagation

Measurements of signals from satellites from global navigation satellite systems are an important tool not only for precision navigation and timing applications, but also for various scientific and remote-sensing applications such as ionosphere monitoring and atmosphere probing using radio occultation. When traveling through turbulent patches of the Earth&rsquo;s ionosphere, these signals can experience scintillation, which is characterized by rapid fluctuations in the amplitude and phase of the received signal. In addition to these fluctuations, the signal can undergo phase transitions that induce cycle slips in the resulting phase measurement. When left uncorrected, cycle slips can lead to large errors in positioning and remote-sensing applications. In this work, we determine how backpropagation based on a single-phase screen model of the ionosphere can help to limit the occurrence of these cycle slips. This approach is applicable for batch post-processing of measurements. Furthermore, our results when applying the method to both simulations and real-life data suggest that backpropagation can correct many of the cycle slips that are generated during severe scintillation. &nbsp;</p