BayGO: Bayesian analysis of ontology term enrichment in microarray data

Abstract Background The search for enriched (aka over-represented or enhanced) ontology terms in a list of genes obtained from microarray experiments is becoming a standard procedure for a system-level analysis. This procedure tries to summarize the information focussing on classification designs such as Gene Ontology, KEGG pathways, and so on, instead of focussing on individual genes. Although it is well known in statistics that association and significance are distinct concepts, only the former approach has been used to deal with the ontology term enrichment problem. Results BayGO implements a Bayesian approach to search for enriched terms from microarray data. The R source-code is freely available at http://blasto.iq.usp.br/~tkoide/BayGO in three versions: Linux, which can be easily incorporated into pre-existent pipelines; Windows, to be controlled interactively; and as a web-tool. The software was validated using a bacterial heat shock response dataset, since this stress triggers known system-level responses. Conclusion The Bayesian model accounts for the fact that, eventually, not all the genes from a given category are observable in microarray data due to low intensity signal, quality filters, genes that were not spotted and so on. Moreover, BayGO allows one to measure the statistical association between generic ontology terms and differential expression, instead of working only with the common significance analysis.

Eutrophication and macroalgal blooms in temperate and tropical coastal waters: nutrient enrichment experiments with Ulva spp.

Receiving coastal waters and estuaries are among the most nutrient-enriched environments on earth, and one of the symptoms of the resulting eutrophication is the proliferation of opportunistic, fast-growing marine seaweeds. Here, we used a widespread macroalga often involved in blooms, Ulva spp., to investigate how supply of nitrogen (N) and phosphorus (P), the two main potential growth-limiting nutrients, influence macroalgal growth in temperate and tropical coastal waters ranging from low- to high-nutrient supplies. We carried out N and P enrichment field experiments on Ulva spp. in seven coastal systems, with one of these systems represented by three different subestuaries, for a total of nine sites. We showed that rate of growth of Ulva spp. was directly correlated to annual dissolved inorganic nitrogen (DIN) concentrations, where growth increased with increasing DIN concentration. Internal N pools of macroalgal fronds were also linked to increased DIN supply, and algal growth rates were tightly coupled to these internal N pools. The increases in DIN appeared to be related to greater inputs of wastewater to these coastal waters as indicated by high delta 15N signatures of the algae as DIN increased. N and P enrichment experiments showed that rate of macroalgal growth was controlled by supply of DIN where ambient DIN concentrations were low, and by P where DIN concentrations were higher, regardless of latitude or geographic setting. These results suggest that understanding the basis for macroalgal blooms, and management of these harmful phenomena, will require information as to nutrient sources, and actions to reduce supply of N and P in coastal waters concerned.

Environmental enrichment blocks ethanol-induced locomotor sensitization and decreases BDNF levels in the prefrontal cortex in mice

The use of addictive drugs can lead to long-term neuroplastic changes in the brain, including behavioral sensitization, a phenomenon related to addiction. Environmental enrichment (EE) is a strategy used to study the effect of environment on the response to several manipulations, including treatment with addictive drugs. Brain-derived neurotrophic factor (BDNF) has been associated with behaviors related to ethanol addiction. The aim of the present study was to evaluate the effects of EE on ethanol-induced behavioral sensitization and BDNF expression. Mice were exposed to EE and then repeatedly treated with a low dose (1.8 g/kg) of ethanol. Another group of mice was first subjected to repeated ethanol treatment according to the behavioral sensitization protocol and then exposed to EE. Environmental enrichment prevented the development of ethanol-induced behavioral sensitization and blocked behavioral sensitization in sensitized mice. Both repeated ethanol and EE decreased BDNF levels in the prefrontal cortex but not in the hippocampus. However, BDNF levels were lower in ethanol-treated mice exposed to EE. These findings suggest that EE can act on the mechanisms implicated in behavioral sensitization, a model for drug-induced neuroplasticity and relapse. Additionally, EE alters BDNF levels, which regulate addiction-related behaviors.

A generalized finite element method with global-local enrichment functions for confined plasticity problems

The main feature of partition of unity methods such as the generalized or extended finite element method is their ability of utilizing a priori knowledge about the solution of a problem in the form of enrichment functions. However, analytical derivation of enrichment functions with good approximation properties is mostly limited to two-dimensional linear problems. This paper presents a procedure to numerically generate proper enrichment functions for three-dimensional problems with confined plasticity where plastic evolution is gradual. This procedure involves the solution of boundary value problems around local regions exhibiting nonlinear behavior and the enrichment of the global solution space with the local solutions through the partition of unity method framework. This approach can produce accurate nonlinear solutions with a reduced computational cost compared to standard finite element methods since computationally intensive nonlinear iterations can be performed on coarse global meshes after the creation of enrichment functions properly describing localized nonlinear behavior. Several three-dimensional nonlinear problems based on the rate-independent J (2) plasticity theory with isotropic hardening are solved using the proposed procedure to demonstrate its robustness, accuracy and computational efficiency.

US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins

Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety. Previously, the US Food and Drug Administration (FDA) cautioned against using various LMWHs interchangeably, however recently, the FDA approved generic versions of LMWH that have not been tested in large clinical trials. This paper highlights the bio-chemical and pharmacological differences between the LMWH preparations that may result in different clinical outcomes, and also reviews the implications and challenges physicians face when generic versions of the original/innovator agents are approved for clinical use.

Enrichment of Pleurotus ostreatus mushrooms with selenium in coffee husks

Pleurotus ostreatus fungus forms an edible mushroom that possesses important nutritional and medicinal properties. Selenium (Se) is essential to human diets and it is in low concentration in the soil, and consequently in food. P. ostreatus was grown in coffee husks enriched with various concentrations of sodium selenite. The biological efficiency of P. ostreatus was affected by the addition of high concentrations of Se. The highest level of Se absorption was obtained by adding 51 mg kg(1) of sodium selenite. The mushrooms from first flush contained more Se than the further flushes. These results demonstrate the great potential of coffee husks in the production of Se-enriched mushrooms and show the ability of this fungus to absorb and biomagnify Se. (C) 2011 Elsevier Ltd. All rights reserved.

A new enrichment space for the treatment of discontinuous pressures in multi-fluid flows

In this work, a new enrichment space to accommodate jumps in the pressure field at immersed interfaces in finite element formulations, is proposed. The new enrichment adds two degrees of freedom per element that can be eliminated by means of static condensation. The new space is tested and compared with the classical P1 space and to the space proposed by Ausas et al (Comp. Meth. Appl. Mech. Eng., Vol. 199, 10191031, 2010) in several problems involving jumps in the viscosity and/or the presence of singular forces at interfaces not conforming with the element edges. The combination of this enrichment space with another enrichment that accommodates discontinuities in the pressure gradient has also been explored, exhibiting excellent results in problems involving jumps in the density or the volume forces. Copyright (c) 2011 John Wiley & Sons, Ltd.

Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription

Abstract Background RNAs transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression. However, the complement of human genes in which introns are transcribed, and the number of intronic transcriptional units and their tissue expression patterns are not known. Results A survey of mRNA and EST public databases revealed more than 55,000 totally intronic noncoding (TIN) RNAs transcribed from the introns of 74% of all unique RefSeq genes. Guided by this information, we designed an oligoarray platform containing sense and antisense probes for each of 7,135 randomly selected TIN transcripts plus the corresponding protein-coding genes. We identified exonic and intronic tissue-specific expression signatures for human liver, prostate and kidney. The most highly expressed antisense TIN RNAs were transcribed from introns of protein-coding genes significantly enriched (p = 0.002 to 0.022) in the 'Regulation of transcription' Gene Ontology category. RNA polymerase II inhibition resulted in increased expression of a fraction of intronic RNAs in cell cultures, suggesting that other RNA polymerases may be involved in their biosynthesis. Members of a subset of intronic and protein-coding signatures transcribed from the same genomic loci have correlated expression patterns, suggesting that intronic RNAs regulate the abundance or the pattern of exon usage in protein-coding messages. Conclusion We have identified diverse intronic RNA expression patterns, pointing to distinct regulatory roles. This gene-oriented approach, using a combined intron-exon oligoarray, should permit further comparative analysis of intronic transcription under various physiological and pathological conditions, thus advancing current knowledge about the biological functions of these noncoding RNAs.

Morphological analysis of Mecosarthron Buquet and Xixuthrus Thomson and Reevaluation of Generic Assignment of Xixuthrus domingoensis Fisher (Coleoptera, Cerambycidae, Prioninae)

The characters defining Mecosarthron Buquet, 1840 and Xixuthrus Thomson 1864 are discussed, along with a historical review of the literature that described and classified these taxa. Through morphological examination of these genera and most of the included species, we addressed the systematic placement of Xixuthrus domingoensis Fisher, 1932 that was placed in Mecosarthron by Ivie (1985). We restore its placement in the genus Xixuthrus. The first description of the female of X. domingoensis is provided, along with comparative redescriptions of Mecosarthron gounellei (Lameere, 1903), and M. buphagus Buquet, 1840. We include a key to the species currently in Mecosarthron.