The small RNA PhrS stimulates synthesis of the Pseudomonas aeruginosa quinolone signal.

Quorum sensing, a cell-to-cell communication system based on small signal molecules, is employed by the human pathogen Pseudomonas aeruginosa to regulate virulence and biofilm development. Moreover, regulation by small trans-encoded RNAs has become a focal issue in studies of virulence gene expression of bacterial pathogens. In this study, we have identified the small RNA PhrS as an activator of PqsR synthesis, one of the key quorum-sensing regulators in P. aeruginosa. Genetic studies revealed a novel mode of regulation by a sRNA, whereby PhrS uses a base-pairing mechanism to activate a short upstream open reading frame to which the pqsR gene is translationally coupled. Expression of phrS requires the oxygen-responsive regulator ANR. Thus, PhrS is the first bacterial sRNA that provides a regulatory link between oxygen availability and quorum sensing, which may impact on oxygen-limited growth in P. aeruginosa biofilms.

Role of peroxynitrite in the redox regulation of cell signal transduction pathways.

Peroxynitrite is a potent oxidant and nitrating species formed from the reaction between the free radicals nitric oxide and superoxide. An excessive formation of peroxynitrite represents an important mechanism contributing to cell death and dysfunction in multiple cardiovascular pathologies, such as myocardial infarction, heart failure and atherosclerosis. Whereas initial works focused on direct oxidative biomolecular damage as the main route of peroxynitrite toxicity, more recent evidence, mainly obtained in vitro, indicates that peroxynitrite also behaves as a potent modulator of various cell signal transduction pathways. Due to its ability to nitrate tyrosine residues, peroxynitrite affects cellular processes dependent on tyrosine phosphorylation. Peroxynitrite also exerts complex effects on the activity of various kinases and phosphatases, resulting in the up- or downregulation of signalling cascades, in a concentration- and cell-dependent manner. Such roles of peroxynitrite in the redox regulation of key signalling pathways for cardiovascular homeostasis, including protein kinase B and C, the MAP kinases, Nuclear Factor Kappa B, as well as signalling dependent on insulin and the sympatho-adrenergic system are presented in detail in this review.

Measurement Errors Should Always Be Incorporated in Phylogenetic Comparative Analysis

The evolution of continuous traits is the central component of comparative analyses in phylogenetics, and the comparison of alternative models of trait evolution has greatly improved our understanding of the mechanisms driving phenotypic differentiation. Several factors influence the comparison of models, and we explore the effects of random errors in trait measurement on the accuracy of model selection. We simulate trait data under a Brownian motion model (BM) and introduce different magnitudes of random measurement error. We then evaluate the resulting statistical support for this model against two alternative models: Ornstein-Uhlenbeck (OU) and accelerating/decelerating rates (ACDC). Our analyses show that even small measurement errors (10%) consistently bias model selection towards erroneous rejection of BM in favour of more parameter-rich models (most frequently the OU model). Fortunately, methods that explicitly incorporate measurement errors in phylogenetic analyses considerably improve the accuracy of model selection. Our results call for caution in interpreting the results of model selection in comparative analyses, especially when complex models garner only modest additional support. Importantly, as measurement errors occur in most trait data sets, we suggest that estimation of measurement errors should always be performed during comparative analysis to reduce chances of misidentification of evolutionary processes.

Placentation in species of phylogenetic importance: the Afrotheria.

Afrotheria, one of four mammalian superorders, comprises elephants, sea cows, hyraxes, aardvark, elephant shrews, tenrecs and golden moles. Their placentas either form an equatorial band or are discoid in shape. The interhemal region, separating fetal and maternal blood, is endotheliochorial in elephants, aardvark and possibly the sea cows, but hemochorial in the remaining orders. There is a secondary epitheliochorial placenta in elephant shrews while a similar structure in tenrecs erodes maternal tissues. Specialized hemophagous regions are a striking characteristic of some of these placentas yet absent in hyraxes, elephant shrews, and golden moles. It is possible that the common ancestor of the Afrotheria had an endotheliochorial placenta. Establishment of a hemochorial condition, as seen in rock hyraxes, elephant shrews, tenrecs, and golden moles, would be a more recent development. The elephant, manatee, and aardvark all have circumferential placentas. Thus the formation of a discoid placenta with a more or less extensive secondary placenta in elephant shrews and tenrecs would also be a derived state.

Estimation of the parameters of the gravitational-wage signal of a coalescing binary system

The statistical theory of signal detection and the estimation of its parameters are reviewed and applied to the case of detection of the gravitational-wave signal from a coalescing binary by a laser interferometer. The correlation integral and the covariance matrix for all possible static configurations are investigated numerically. Approximate analytic formulas are derived for the case of narrow band sensitivity configuration of the detector.

Divergent signal-to-noise ratio and stochastic resonance in monostable systems

We present a class of systems for which the signal-to-noise ratio always increases when increasing the noise and diverges at infinite noise level. This new phenomenon is a direct consequence of the existence of a scaling law for the signal-to-noise ratio and implies the appearance of stochastic resonance in some monostable systems. We outline applications of our results to a wide variety of systems pertaining to different scientific areas. Two particular examples are discussed in detail.

Manipulating the sensitivity of signal-induced repression: quantification and consequences of altered brinker gradients.

Traditionally, the analysis of gene regulatory regions suffered from the caveat that it was restricted to artificial contexts (e.g. reporter constructs of limited size). With the advent of the BAC recombineering technique, genomic constructs can now be generated to test regulatory elements in their endogenous environment. The expression of the transcriptional repressor brinker (brk) is negatively regulated by Dpp signaling. Repression is mediated by small sequence motifs, the silencer elements (SEs), that are present in multiple copies in the regulatory region of brk. In this work, we manipulated the SEs in the brk locus. We precisely quantified the effects of the individual SEs on the Brk gradient in the wing disc by employing a 1D data extraction method, followed by the quantification of the data with reference to an internal control. We found that mutating the SEs results in an expansion of the brk expression domain. However, even after mutating all predicted SEs, repression could still be observed in regions of maximal Dpp levels. Thus, our data point to the presence of additional, low affinity binding sites in the brk locus.

Effect of the output of the system in signal detection

We analyze the consequences that the choice of the output of the system has in the efficiency of signal detection. It is shown that the output signal and the signal-to-noise ratio (SNR), used to characterize the phenomenon of stochastic resonance, strongly depend on the form of the output. In particular, the SNR may be enhanced for an adequate output.

Comparative genomics of the vertebrate insulin/TOR signal transduction pathway: A network-level analysis of selective pressures

Complexity of biological function relies on large networks of interacting molecules. However, the evolutionary properties of these networks are not fully understood. It has been shown that selective pressures depend on the position of genes in the network. We have previously shown that in the Drosophila insulin/target of rapamycin (TOR) signal transduction pathway there is a correlation between the pathway position and the strength of purifying selection, with the downstream genes being most constrained. In this study, we investigated the evolutionary dynamics of this well-characterized pathway in vertebrates. More specifically, we determined the impact of natural selection on the evolution of 72 genes of this pathway. We found that in vertebrates there is a similar gradient of selective constraint in the insulin/TOR pathway to that found in Drosophila. This feature is neither the result of a polarity in the impact of positive selection nor of a series of factors affecting selective constraint levels (gene expression level and breadth, codon bias, protein length, and connectivity). We also found that pathway genes encoding physically interacting proteins tend to evolve under similar selective constraints. The results indicate that the architecture of the vertebrate insulin/TOR pathway constrains the molecular evolution of its components. Therefore, the polarity detected in Drosophila is neither specific nor incidental of this genus. Hence, although the underlying biological mechanisms remain unclear, these may be similar in both vertebrates and Drosophila.

Isolation of a novel monkey adenovirus reveals a new phylogenetic clade in the evolutionary history of simian adenoviruses

Adenoviruses of primates include human (HAdV) and simian (SAdV) isolates classified into 8 species (Human Adenovirus A to G, and Simian Adenovirus A). In this study, a novel adenovirus was isolated from a colony of cynomolgus macaques (Macaca fascicularis) and subcultured in VERO cells. Its complete genome was purified and a region encompassing the hexon gene, the protease gene, the DNA binding protein (DBP) and the 100 kDa protein was amplified by PCR and sequenced by primer walking. Sequence analysis of these four genes showed that the new isolate had 80% identity to other primate adenoviruses and lacked recombination events. The study of the evolutionary relationships of this new monkey AdV based on the combined sequences of the four genes supported a close relationship to SAdV-3 and SAdV-6, lineages isolated from Rhesus monkeys. The clade formed by these three types is separated from the remaining clades and establishes a novel branch that is related to species HAdV-A, F and G. However, the genetic distance corresponding to the newly isolated monkey AdV considerably differs from these as to belong to a new, not yet established species. Results presented here widen our knowledge on SAdV and represents an important contribution to the understanding of the evolutionary history of primate adenoviruses.

Revision to the SUDAS Traffic Signal Standards – Phase 2, Final Report, May 2012

This report provides a summary of the updates to the traffic signal content within the Iowa Statewide Urban Design and Specifications (SUDAS) Design Manual Chapter 13 and Standard Specifications Division 8. Major focal points included pole footing design, cabinets and controllers, monitoring systems, communications systems, and figure updates. This work was completed through a project task force with a variety of participants (contractors, Iowa Department of Transportation, city traffic engineers, consultant, vendors, and University research and support staff).

Connections between signal processing and complex analysis

We describe one of the research lines of the Grup de Teoria de Funcions de la UAB UB, which deals with sampling and interpolation problems in signal analysis and their connections with complex function theory.