Characterization of oxylipins and dioxygenase genes in the asexual fungus Aspergillus niger

Background  

Aspergillus niger is an ascomycetous fungus that is known to reproduce through asexual spores, only. Interestingly, recent genome analysis of A. niger has revealed the presence of a full complement of functional genes related to sexual reproduction [1]. An example of such genes are the dioxygenase genes which in Aspergillus nidulans, have been shown to be connected to oxylipin production and regulation of both sexual and asexual sporulation [2–4]. Nevertheless, the presence of sex related genes alone does not confirm sexual sporulation in A. niger.     

Envelope structure of Synechococcus sp. WH8113, a nonflagellated swimming cyanobacterium

Background  

Many bacteria swim by rotating helical flagellar filaments [1]. Waterbury et al. [15] discovered an exception, strains of the cyanobacterium Synechococcus that swim without flagella or visible changes in shape. Other species of cyanobacteria glide on surfaces [2,7]. The hypothesis that Synechococcus might swim using traveling surface waves [6,13] prompted this investigation.     

Modeling the effects of a Staphylococcal Enterotoxin B (SEB) on the apoptosis pathway

Background  

The lack of detailed understanding of the mechanism of action of many biowarfare agents poses an immediate challenge to biodefense efforts. Many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis [1–4]. For example, pathogen-produced exotoxins such as Staphylococcal Enterotoxin B (SEB) and Anthrax Lethal Factor (LF) have been shown to disrupt the Fas-mediated apoptotic pathway [2, 4]. To evaluate how these agents affect these pathways it is first necessary to understand the dynamics of a normally functioning apoptosis network. This can then serve as a baseline against which a pathogen perturbed system can be compared. Such comparisons can expose both the proteins most susceptible to alteration by the agent as well as the most critical reaction rates to better instill control on a biological network.     

Sample phenotype clusters in high-density oligonucleotide microarray data sets are revealed using Isomap,a nonlinear algorithm

Background  

Life processes are determined by the organism's genetic profile and multiple environmental variables. However the interaction between these factors is inherently non-linear [1]. Microarray data is one representation of the nonlinear interactions among genes and genes and environmental factors. Still most microarray studies use linear methods for the interpretation of nonlinear data. In this study, we apply Isomap, a nonlinear method of dimensionality reduction, to analyze three independent large Affymetrix high-density oligonucleotide microarray data sets.     

HTS-Corrector: software for the statistical analysis and correction of experimental high-throughput screening data

MOTIVATION: High-throughput screening (HTS) plays a central role in modern drug discovery, allowing for testing of >100,000 compounds per screen. The aim of our work was to develop and implement methods for minimizing the impact of systematic error in the analysis of HTS data. To the best of our knowledge, two new data correction methods included in HTS-Corrector are not available in any existing commercial software or freeware. RESULTS: This paper describes HTS-Corrector, a software application for the analysis of HTS data, detection and visualization of systematic error, and corresponding correction of HTS signals. Three new methods for the statistical analysis and correction of raw HTS data are included in HTS-Corrector: background evaluation, well correction and hit-sigma distribution procedures intended to minimize the impact of systematic errors. We discuss the main features of HTS-Corrector and demonstrate the benefits of the algorithms.     

Ebbie: automated analysis and storage of small RNA cloning data using a dynamic web server

Background  

DNA sequencing is used ubiquitously: from deciphering genomes[1] to determining the primary sequence of small RNAs (smRNAs) [2–5]. The cloning of smRNAs is currently the most conventional method to determine the actual sequence of these important regulators of gene expression. Typical smRNA cloning projects involve the sequencing of hundreds to thousands of smRNA clones that are delimited at their 5' and 3' ends by fixed sequence regions. These primers result from the biochemical protocol used to isolate and convert the smRNA into clonable PCR products. Recently we completed a smRNA cloning project involving tobacco plants, where analysis was required for ~700 smRNA sequences[6]. Finding no easily accessible research tool to enter and analyze smRNA sequences we developed Ebbie to assist us with our study.     

Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at receptor-binding interfaces

Background  

Interleukin-4 (IL4) is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths [1]. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution.     

Distinguishing HIV-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples

Background  

HIV can evolve drug resistance rapidly in response to new drug treatments, often through a combination of multiple mutations [1–3]. It would be useful to develop automated analyses of HIV sequence polymorphism that are able to predict drug resistance mutations, and to distinguish different types of functional roles among such mutations, for example, those that directly cause drug resistance, versus those that play an accessory role. Detecting functional interactions between mutations is essential for this classification. We have adapted a well-known measure of evolutionary selection pressure (K _a /K _s ) and developed a conditional K _a /K _s approach to detect important interactions.     

Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1

Background  

Systemic acquired resistance (SAR) is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA) is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR) genes. Arabidopsis n on-expressor of PR1 (NPR1) is a regulatory gene of the SA signal pathway [1–3]. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis.     

A response to information criterion-based clustering with order-restricted candidate profiles in short time-course microarray experiments

Background  

For gene expression data obtained from a time-course microarray experiment, Liu et al. [1] developed a new algorithm for clustering genes with similar expression profiles over time. Performance of their proposal was compared with three other methods including the order-restricted inference based methodology of Peddada et al. [2, 3]. In this note we point out several inaccuracies in Liu et al. [1] and conclude that the order-restricted inference based methodology of Peddada et al. (programmed in the software ORIOGEN) indeed operates at the desired nominal Type 1 error level, an important feature of a statistical decision rule, while being computationally substantially faster than indicated by Liu et al. [1].     

Multiple source genes of HAmo SINE actively expanded and ongoing retroposition in cyprinid genomes relying on its partner LINE

Background  

We recently characterized HAmo SINE and its partner LINE in silver carp and bighead carp based on hybridization capture of repetitive elements from digested genomic DNA in solution using a bead-probe [1]. To reveal the distribution and evolutionary history of SINEs and LINEs in cyprinid genomes, we performed a multi-species search for HAmo SINE and its partner LINE using the bead-probe capture and internal-primer-SINE polymerase chain reaction (PCR) techniques.     

Blochmannia endosymbionts improve colony growth and immune defence in the ant Camponotus fellah

Background  

Microorganisms are a large and diverse form of life. Many of them live in association with large multicellular organisms, developing symbiotic relations with the host and some have even evolved to form obligate endosymbiosis [1]. All Carpenter ants (genus Camponotus) studied hitherto harbour primary endosymbiotic bacteria of the Blochmannia genus. The role of these bacteria in ant nutrition has been demonstrated [2] but the omnivorous diet of these ants lead us to hypothesize that the bacteria might provide additional advantages to their host. In this study, we establish links between Blochmannia, growth of starting new colonies and the host immune response.     

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

Background  

Cardiomyocyte contraction is initiated by influx of extracellular calcium through voltage-gated calcium channels. These oligomeric channels utilize auxiliary β subunits to chaperone the pore-forming α subunit to the plasma membrane, and to modulate channel electrophysiology [1]. Several β subunit family members are detected by RT-PCR in the embryonic heart. Null mutations in mouse β2, but not in the other three β family members, are embryonic lethal at E10.5 due to defects in cardiac contractility [2]. However, a drawback of the mouse model is that embryonic heart rhythm is difficult to study in live embryos due to their intra-uterine development. Moreover, phenotypes may be obscured by secondary effects of hypoxia. As a first step towards developing a model for contributions of β subunits to the onset of embryonic heart rhythm, we characterized the structure and expression of β2 subunits in zebrafish and other teleosts.     

Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr

Background  

Tpr is a large protein with an extended coiled-coil domain that is localized within the nuclear basket of the nuclear pore complex. Previous studies [1] involving antibody microinjection into mammalian cells suggested a role for Tpr in nuclear export of proteins via the CRM1 export receptor. In addition, Tpr was found to co-immunoprecipitate with importins α and β from Xenopus laevis egg extracts [2], although the function of this is unresolved. Yeast Mlp1p and Mlp2p, which are homologous to vertebrate Tpr, have been implicated in mRNA surveillance to retain unspliced mRNAs in the nucleus[3, 4]. To augment an understanding of the role of Tpr in nucleocytoplasmic trafficking, we explored the interactions of recombinant Tpr with the karyopherins CRM1, importin β and importin α by solid phase binding assays. We also investigated the conditions required for nuclear import of Tpr using an in vitro assay.     

ProMEX: a mass spectral reference database for proteins and protein phosphorylation sites

Background  

In the last decade, techniques were established for the large scale genome-wide analysis of proteins, RNA, and metabolites, and database solutions have been developed to manage the generated data sets. The Golm Metabolome Database for metabolite data (GMD) represents one such effort to make these data broadly available and to interconnect the different molecular levels of a biological system [1]. As data interpretation in the light of already existing data becomes increasingly important, these initiatives are an essential part of current and future systems biology.     

Supported treadmill training to establish walking in non-ambulatory patients early after stroke

Background  

It has been reported that only half of the non-ambulatory stroke patients admitted to inpatient rehabilitation in Australia learn to walk again [1]. Treadmill walking with partial weight support via an overhead harness is a relatively new intervention that is designed to train walking. The main objective of this randomised controlled trail is to determine whether treadmill walking with partial weight support via an overhead harness is effective at establishing independent walking (i) more often, (ii) earlier and (iii) with a better quality of walking, than current physiotherapy intervention for non-ambulatory stroke patients.     

P2 receptors in atherosclerosis and postangioplasty restenosis

Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [1–3]. Extracellular nucleotides that are released from a variety of arterial and blood cells [4] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which is known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [5]. In addition, P2 receptors mediate many other functions, including platelet aggregation, leukocyte adherence, and arterial vasomotoricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that up-regulation and activation of P2Y₂ receptors in rabbit arteries mediates intimal hyperplasia [6]. In addition, up-regulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [7] and in coronary arteries of diabetic dyslipidemic pigs [8]. It has been proposed that up-regulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [9]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty.     

Identification of coherent patterns in gene expression data using an efficient biclustering algorithm and parallel coordinate visualization

Background  

The DNA microarray technology allows the measurement of expression levels of thousands of genes under tens/hundreds of different conditions. In microarray data, genes with similar functions usually co-express under certain conditions only [1]. Thus, biclustering which clusters genes and conditions simultaneously is preferred over the traditional clustering technique in discovering these coherent genes. Various biclustering algorithms have been developed using different bicluster formulations. Unfortunately, many useful formulations result in NP-complete problems. In this article, we investigate an efficient method for identifying a popular type of biclusters called additive model. Furthermore, parallel coordinate (PC) plots are used for bicluster visualization and analysis.     

Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

Background  

The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC). Genetic studies in zebrafish and mice have established that the Hedgehog (Hh)-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE), which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia [1, 2]. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA) skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1) for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1).     

Functional Annotation,Genome Organization and Phylogeny of the Grapevine (<Emphasis Type="Italic">Vitis vinifera</Emphasis>) Terpene Synthase Gene Family Based on Genome Assembly,FLcDNA Cloning,and Enzyme Assays

Background  

Terpenoids are among the most important constituents of grape flavour and wine bouquet, and serve as useful metabolite markers in viticulture and enology. Based on the initial 8-fold sequencing of a nearly homozygous Pinot noir inbred line, 89 putative terpenoid synthase genes (VvTPS) were predicted by in silico analysis of the grapevine (Vitis vinifera) genome assembly [1]. The finding of this very large VvTPS family, combined with the importance of terpenoid metabolism for the organoleptic properties of grapevine berries and finished wines, prompted a detailed examination of this gene family at the genomic level as well as an investigation into VvTPS biochemical functions.