Genome-wide analysis of mammalian promoter architecture and evolution

Mammalian promoters can be separated into two classes, conserved TATA box-enriched promoters, which initiate at a welldefined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation.

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5'-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial release.

Evolutionary turnover of mammalian transcription start sites

Alignments of homologous genomic sequences are widely used to identify functional genetic elements and study their evolution. Most studies tacitly equate homology of functional elements with sequence homology. This assumption is violated by the phenomenon of turnover, in which functionally equivalent elements reside at locations that are nonorthologous at the sequence level. Turnover has been demonstrated previously for transcription-factor-binding sites. Here, we show that transcription start sites of equivalent genes do not always reside at equivalent locations in the human and mouse genomes. We also identify two types of partial turnover, illustrating evolutionary pathways that could lead to complete turnover. These findings suggest that the signals encoding transcription start sites are highly flexible and evolvable, and have cautionary implications for the use of sequence-level conservation to detect gene regulatory elements.

Transcriptional network dynamics in macrophage activation

Transcriptional regulatory networks govern cell differentiation and the cellular response to external stimuli. However, mammalian model systems have not yet been accessible for network analysis. Here, we present a genome-wide network analysis of the transcriptional regulation underlying the mouse macrophage response to bacterial lipopolysaccharide (LPS). Key to uncovering the network structure is our combination of time-series cap analysis of gene expression with in silico prediction of transcription factor binding sites. By integrating microarray and qPCR time-series expression data with a promoter analysis, we find dynamic subnetworks that describe how signaling pathways change dynamically during the progress of the macrophage LPS response, thus defining regulatory modules characteristic of the inflammatory response. In particular, our integrative analysis enabled us to suggest novel roles for the transcription factors ATF-3 and NRF-2 during the inflammatory response. We believe that our system approach presented here is applicable to understanding cellular differentiation in higher eukaryotes. (c) 2006 Elsevier Inc. All rights reserved.

An analysis of US greenhouse gas cap-and-trade proposals using a forward-looking economic model

We develop a forward-looking version of the recursive dynamic MIT Emissions Prediction and Policy Analysis (EPPA) model, and apply it to examine the economic implications of proposals in the US Congress to limit greenhouse gas (GHG) emissions. We find that shocks in the consumption path are smoothed out in the forward-looking model and that the lifetime welfare cost of GHG policy is lower than in the recursive model, since the forward-looking model can fully optimize over time. The forward-looking model allows us to explore issues for which it is uniquely well suited, including revenue-recycling and early action crediting. We find capital tax recycling to be more welfare-cost reducing than labor tax recycling because of its long-term effect on economic growth. Also, there are substantial incentives for early action credits; however, when spread over the full horizon of the policy they do not have a substantial effect on lifetime welfare costs.

Observations of the northern seasonal polar cap on Mars II: HiRISE photometric analysis of evolution of northern polar dunes in spring

We present an overview of our analyses of HiRISE observations of spring evolution of selected dune areas of the north polar erg. The north polar erg is covered annually by seasonal volatile ice layer, a mixture of CO2 and H2O with mineral dust contamination. In spring, this layer sublimes creating visually enigmatic phenomena, e.g. dark and bright fan-shaped deposits, dark–bright–dark bandings, dark down-slope streaks, and seasonal polygonal cracks. Similar phenomena in southern polar areas are believed to be related to the specific process of solid-state greenhouse effect. In the north, it is currently unclear if the solid-state greenhouse effect is able to explain all the observed phenomena especially because the increased influence of H2O on the time scales of this process has not yet been quantified. HiRISE observations of our selected locations show that the ground exhibits a temporal behaviour similar to the one observed in the southern polar areas: a brightening phase starting close to the spring equinox with a subsequent darkening towards summer solstice. The resolution of HiRISE enabled us to study dunes and substrate individually and even distinguish between different developments on windward and slip face sides of single dunes. Differences in the seasonal evolution between steep slip faces and flatter substrate and windward sides of dunes have been identified and compared to CRISM data of CO2 and H2O distributions on dunes. We also observe small scale dark blotches that appear in early observations and tend to sustain a low reflectivity throughout the spring. These blotches can be regarded as the analogue of dark fan deposits in southern polar areas, leading us to the conclusion that both martian polar areas follow similar spring evolutions.

Parametric analysis on bridge reinforced concrete elevated pile-cap foundations

Current design practices recommend to comply with the capacity protection principle, which pays special attention to ensuring an elastic response of the foundations under ground motion events. However, in cases such as elevated reinforced concrete (RC) pile-cap foundation typologies, this design criterion may lead to conservative designs, with excessively high construction costs. Reinforced concrete elevated pile-cap foundations is a system formed by a group of partially embedded piles connected through an aboveground stayed cap and embedded in soil. In the cases when they are subjected to ground motions, the piles suffer large bending moments that make it difficult to maintain their behavior within the elastic range of deformations. Aiming to make an in-depth analysis of the nonlinear behavior of elevated pile-cap foundations, a cyclic loading test was performed on a concrete 2x3 pile configuration specimen of elevated pile-cap foundation. Two results of this test, the failure mechanism and the ductile behavior, were used for the calibration of a numerical model built in OpenSees framework, by using a pushover analysis. The calibration of the numerical model enabled an in-depth study of the seismic nonlinear response of this kind of foundations. A parametric analysis was carried for this purpose, aiming to study how sensitive RC elevated pile-cap foundations are, when subjected to variations in the diameter of piles, reinforcement ratios, external loads, soil density or multilayer configurations. This analysis provided a set of ductility factors that can be used as a reference for design practices and which correspond to each of the cases analyzed.

An Analysis of the Capitalisation of CAP Payments into Land Rental Rates in Ireland. Factor Markets Working Document No. 68, August 2013

EDITED VERSION SOON TO BE PUBLISHED In this paper the effect of decoupling on the capitalisation of agricultural subsidies into agricultural rents in Ireland are analysed using a dynamic rental equations estimated with a two step system GMM estimator that accounts for expectation error and endogenous regressors. The findings illustrate the importance of institutional details in determining the extent to which subsidies are capitalised. In the period prior to decoupling Pillar 1 subsidies were highly capitalised into Irish agricultural rents in both the short and the long run. Depending on the farm system considered between 58 to 80 cents per euro of subsidies were capitalised into agricultural rents. In the post decoupling period the rate at which Pillar 1 subsidies are capitalised into Irish agricultural rents is found to have declined. This change is likely due to short term character of the Irish agricultural land rental market, where 11 month rental periods predominate, and the freedom that the 2003 reform of the CAP offered farmers to consolidate entitlements established on rented land. The generally very short term nature of Irish agricultural rental contracts offered farmers an opportunity to consolidate entitlements that is unlikely to have arisen in other Member States with agricultural land rental markets characterised by long term contracts. The results in both the pre and post decoupling periods highlight the high degree of inertia of agricultural rents in Ireland, and the importance of accounting for dynamics when investigating the capitalisation of agricultural subsidies into land rents. The high degree of inertia in rents means that the impact of previously capitalised agricultural policy persists through time.

Fluorescence and reflectance spectroscopy for identification of atherosclerosis in human carotid arteries using principal components analysis

Objectives: The aim of this work was to verify the differentiation between normal and pathological human carotid artery tissues by using fluorescence and reflectance spectroscopy in the 400- to 700-nm range and the spectral characterization by means of principal components analysis. Background Data: Atherosclerosis is the most common and serious pathology of the cardiovascular system. Principal components represent the main spectral characteristics that occur within the spectral data and could be used for tissue classification. Materials and Methods: Sixty postmortem carotid artery fragments (26 non-atherosclerotic and 34 atherosclerotic with non-calcified plaques) were studied. The excitation radiation consisted of a 488-nm argon laser. Two 600-mu m core optical fibers were used, one for excitation and one to collect the fluorescence radiation from the samples. The reflectance system was composed of a halogen lamp coupled to an excitation fiber positioned in one of the ports of an integrating sphere that delivered 5 mW to the sample. The photo-reflectance signal was coupled to a 1/4-m spectrograph via an optical fiber. Euclidean distance was then used to classify each principal component score into one of two classes, normal and atherosclerotic tissue, for both fluorescence and reflectance. Results: The principal components analysis allowed classification of the samples with 81% sensitivity and 88% specificity for fluorescence, and 81% sensitivity and 91% specificity for reflectance. Conclusions: Our results showed that principal components analysis could be applied to differentiate between normal and atherosclerotic tissue with high sensitivity and specificity.

Analysis of two reinforced concrete pile caps with embedded sockets in the presence of a locking beam

The present research studies the behavior of reinforced concrete locking beams supported by two capped piles with the socket embedded; used as connections for pre-cast concrete structures. The effect provoked by locking the beam on the pile-caps when supported by the lateral socket walls was evaluated. Three-dimensional numerical analyses using software based on the finite element method (FEM) were developed considering the nonlinear physical behavior of the material. To evaluate the adopted software, a comparative analysis was made using the numerical and experimented results obtained from other software. In the pile caps studied, a variation in the wall thickness, socket interface, strut angle inclination and action on beam. The results show that the presence of a beam does not significantly change pile cap behavior and that the socket wall is able to effectively transfer the force from the beam to the pile caps. By the tensions on the bars of longitudinal reinforcement, it was possible to obtain the force on the tie and the strut angle inclination before the collapse of models. It was found that the angles present more inclinations than those used in the design, which was made based on a strut-and-tie model. More results are available at http://www.set.eesc.usp.br/pdf/download/2009ME_RodrigoBarros.pdf

Genetic structure and mating system of Euterpe edulis Mart. populations: A comparative analysis using microsatellite and allozyme markers

A comparative study between microsatellite and allozyme markers was conducted on the genetic structure and mating system in natural populations of Euterpe edulis Mart. Three cohorts, including seedlings, saplings, and adults, were examined in 4 populations using 10 allozyme loci and 10 microsatellite loci. As expected, microsatellite markers had a much higher degree of polymorphism than allozymes, but estimates of multilocus outcrossing rate ((t) over cap (m) = 1.00), as well as estimates of genetic structure (F(IS), G(ST)), were similar for the 2 sets of markers. Estimates of R(ST), for microsatellites, were higher than those of GST, but results of both statistics revealed a close agreement for the genetic structure of the species. This study provides support for the important conclusion that allozymes are still useful and reliable markers to estimate population genetic parameters. Effects of sample size on estimates from hypervariable loci are also discussed in this paper.

Analysis of long-term light-trap data for Helicoverpa spp. (Lepidoptera : Noctuidae) in Australia: the effect of climate and crop host plants

Regression analyses of a long series of light-trap catches at Narrabri, Australia, were used to describe the seasonal dynamics of Helicoverpa armigera (Hubner). The size of the second generation was significantly related to the size of the first generation, to winter rainfall, which had a positive effect, and to spring rainfall which had a negative effect. These variables accounted for up to 96% of the variation in size of the second generation from year to year. Rainfall and crop hosts were also important for the size of the third generation. The area and tonnage of many potential host crops were significantly correlated with winter rain. When winter rain was omitted from the analysis, the sizes of both the second and third generations could be expressed as a function of the size of the previous generation and of the areas planted to lucerne, sorghum and maize. Lucerne and maize always had positive coefficients and sorghum a negative one. We extended our analysis to catches of H. punctigera (Wallengren), which declines in abundance after the second generation. Winter rain had a positive effect on the sizes of the second and third generations, and rain in spring or early summer had a negative effect. Only the area grown to lucerne had a positive effect on abundance. Forecasts of pest levels from a few months to a few weeks in advance are discussed, along with the improved understanding of the seasonal dynamics of both species and the significance of crops in the management of insecticide resistance for H. armigera.