Mitochondrial peroxiredoxins.

Mitochondria are the major intracellular sites of oxygen consumption producing reactive oxygen species (ROS) as toxic by-products of oxidative phosphorylation, primarily via electron leakage from the respiratory chain. The resultant types of chemical damage to lipids, DNA and proteins are described as well as the broader implications for the involvement of ROS in disease onset and progression. The relative contributions of mitochondrial, enzyme-linked, antioxidant defence systems to tissue protection are also reviewed as is the emerging importance of the peroxiredoxin family in general to H2O2-mediated signalling The constituent enzymes of the mitochondrial PrxIII pathway are discussed in detail including the roles of PrxIII and PrxV in their capacities as typical 2-cys and atypical 2-cys thioredoxin-dependent hydroperoxide reductases, respectively.

UV-B signaling pathways with different fluence-rate response profiles are distinguished in mature Arabidopsis leaf tissue by requirement for UVR8, HY5, and HYH.

UV-B signaling is an important but poorly understood aspect of light responsiveness in plants. Arabidopsis (Arabidopsis thaliana) UV RESISTANCE LOCUS8 (UVR8) is a recently identified UV-B-specific signaling component that regulates UV-protective responses. Using the uvr8 mutant, we defined genetically distinct UVR8-dependent and UVR8-independent pathways that stimulate different sets of genes in mature Arabidopsis leaf tissue.

The application of genetic algorithms in behavioural ecology, illustrated with a model of anti-predator vigilance.

We develop a genetic algorithm (GA) approach to a well-known model of vigilance behaviour in a group of animals. We first demonstrate that the GA approach can provide a good match to analytic solutions to the original model. We demonstrate that a GA can be used to find the evolutionarily stable strategies in a model relevant to behavioural ecology where the fitness of each strategy is determined by the frequencies of different strategies in the population.

A new erythrose 4-phosphate dehydrogenase coupled assay for transketolase.

The standard assay for transketolase (E.C 2.2.

Early growth conditions, phenotypic development and environmental change.

Phenotypic development is the result of a complex interplay involving the organism's own genetic make-up and the environment it experiences during development. The latter encompasses not just the current environment, but also indirect, and sometimes lagged, components that result from environmental effects on its parents that are transmitted to their developing offspring in various ways and at various stages. These environmental effects can simply constrain development, for example, where poor maternal condition gives rise to poorly provisioned, low-quality offspring.

Adenosine receptor ligands protect against a combination of apoptotic and necrotic cell death in cerebellar granule neurons.

Agonists at A(1) receptors and antagonists at A(2A) receptors are known to be neuroprotective against excitotoxicity. We set out to clarify the mechanisms involved by studying interactions between adenosine receptor ligands and endogenous glutamate in cultures of rat cerebellar granule neurons (CGNs). Glutamate and the selective agonist N-methyl-D: -aspartate (NMDA), applied to CGNs at 9 div (days in vitro), both induced cell death in a concentration-dependent manner, which was attenuated by treatment with the NMDA receptor antagonists dizocilpine, D: -2-amino-5-phosphono-pentanoic acid (D: -AP5) or kynurenic acid (KYA), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX).

Suppression of inflammatory and immune responses by the A(2A) adenosine receptor: an introduction.

The purine nucleoside adenosine has been described as a 'retaliatory metabolite' by virtue of its ability to function in an autocrine manner to modify the activity of a range of cell types following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by the binding of adenosine to any of four G-protein-coupled adenosine receptors. Most of the anti-inflammatory effects of adenosine have been assigned to the adenosine A(2A) receptor subtype, which is expressed in many immune and inflammatory cells.

Cauliflower mosaic virus protein P6 is a suppressor of RNA silencing.

We infected a transgenic Arabidopsis line (GxA), containing an amplicon-silenced 35S : : GFP transgene, with cauliflower mosaic virus (CaMV), a plant pararetrovirus with a DNA genome. Systemically infected leaves showed strong GFP fluorescence and amplicon transcripts were detectable in Northern blots, indicating that silencing of GFP had been suppressed during CaMV-infection. Transgenic Arabidopsis lines expressing CaMV protein P6, the major genetic determinant of symptom severity, were crossed with GxA.

Allosteric modulation of heterodimeric G-protein-coupled receptors.

G-protein-coupled receptors (GPCRs) are, and will probably remain, the most tractable class of targets for the development of small-molecule therapeutic medicines. Currently, all approved GPCR-directed medicines are agonists or antagonists at orthosteric binding sites - except for the calcimimetic cinacalcet, which is a positive allosteric modulator of Ca(2+)-sensing receptors, and maraviroc, an allosteric inhibitor of CC-chemokine receptor (CCR) 5. It is now widely accepted that GPCRs exist and might function as dimers, and there is growing evidence for the physiological presence and relevance of GPCR heterodimers.

Cellular response to low adhesion nanotopographies.

This review focuses on how cells respond to low-adhesion nanotopographies. In order to do this, fabrication techniques, how cells may locate nanofeatures through the use of filopodia and possible mechanotransductive mechanisms are discussed. From this, examples of low-adhesion topographies and sizes and arrangements that may lead to low-adhesion are discussed.

Metacaspase 2 of Trypanosoma brucei is a calcium-dependent cysteine peptidase active without processing.

Metacaspases are cysteine peptidases that are distantly related to the caspases, for which proteolytic processing is central to their activation. Here, we show that recombinant metacaspase 2 (MCA2) from Trypanosoma brucei has arginine/lysine-specific, Ca(2+)-dependent proteolytic activity. Autocatalytic processing of MCA2 occurred after Lys55 and Lys268; however, this was shown not to be required for the enzyme to be proteolytically active.

Energy replacement attenuates the effects of prior moderate exercise on postprandial metabolism in overweight/obese men.

Background: The extent to which exercise-induced changes to postprandial metabolism are dependant on the associated energy deficit is not known.

Objective: To determine the effects of exercise, with and without energy replacement, on postprandial metabolism.

Design: Each subject underwent three 2-day trials in random order.

BugView: a tool for genome visualization and comparison.

We describe BugView, a cross-platform application for presenting and comparing the genomes of bacteria or eukaryotes. We give particular emphasis to its use in comparing the genes of related bacterial genomes, and consider different methods of automating the preparation of genome comparison files, including a new web-based facility. Ways of using BugView to study and present the internal structure of genomes are also discussed.

Regulating gene transcription in response to cyclic AMP elevation.

Many of the effects of prototypical second messenger cyclic adenosine 3',5'-monophosphate (cAMP) on complex processes such as the regulation of fuel metabolism, spermatogenesis and steroidogenesis are mediated via changes in target gene transcription. A large body of research has defined members of the cAMP-response element binding (CREB) protein family as the principal mediators of positive changes in gene expression in response to cAMP following phosphorylation by cAMP-dependent protein kinase (PKA). However, persistent observations of cAMP-mediated induction of specific genes occurring via PKA-independent mechanisms have challenged the generality of the PKA-CREB pathway.

Exercise-induced changes in calcium handling in left ventricular cardiomyocytes.

Regular exercise training results in beneficial adaptation of the heart by improving its contractile capacity. This has important consequences for both healthy individuals and those with depressed myocardial function, e.g.

A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization.

G protein-coupled receptors are one of the most actively studied families of proteins. However, despite the ubiquity of protein dimerization and oligomerization as a structural and functional motif in biology, until the last decade they were generally considered as monomeric, non-interacting polypeptides. For the metabotropic glutamate-like group of G protein-coupled receptors, it is now firmly established that they exist and function as dimers or, potentially, even within higher-order structures.

Neurotoxicity of tryptophan metabolites.

The metabolism of tryptophan by the kynurenine pathway leads to the production of several neurotoxic compounds, some of which have been associated with neurological disorders. Recent investigation of some relevant compounds in this pathway has provided further evidence of their neurotoxicity.

cAMP-specific phosphodiesterase-4D5 (PDE4D5) provides a paradigm for understanding the unique non-redundant roles that PDE4 isoforms play in shaping compartmentalized cAMP cell signalling.

The PDE4 (phosphodiesterase-4) enzyme family consists of a distinct array of N-terminal splice variant isoforms arising from four subfamily genes (4A, 4B, 4C and 4D). These all hydrolyse specifically the intracellular second messenger cAMP. Although identical in catalytic function, each isoform appears to serve a non-superfluous regulatory role.

The alternative splicing factor hnRNP A1 is up-regulated during virus-infected epithelial cell differentiation and binds the human papillomavirus type 16 late regulatory element.

Human papillomavirus type 16 (HPV16) infects anogenital epithelia and is the etiological agent of cervical cancer. We showed previously that HPV16 infection regulates the key splicing/alternative splicing factor SF2/ASF and that virus late transcripts are extensively alternatively spliced. hnRNP A1 is the antagonistic counterpart of SF2/ASF in alternative splicing.

Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy.

Cardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload-induced cardiomyocyte hypertrophy is associated with depressed contractile function, physiological hypertrophy after exercise training associates with preserved or increased inotropy. We determined the activation state of myocardial Akt signaling with downstream substrates and fetal gene reactivation in exercise-induced physiological and pressure overload-induced pathological hypertrophies.

Regulation of RNA polymerase III transcription during mammalian cell growth.

RNA polymerase (pol) III manufactures transfer RNAs, 5S ribosomal RNA and several other untranslated RNA molecules that are essential components of the biosynthetic process. Accordingly, transcription by pol III is closely coupled to cellular growth rate. In mammals, stringent regulation of pol III output is achieved through the concerted action of various mechanisms that target the essential pol III-specific transcription factor TFIIIB.

Matters of the heart: the physiology of cardiac function and failure.

Heart failure as a result of a myocardial infarction (MI) is a common condition with a poor prognosis. The adaptive changes in the surviving myocardium appear to be insufficient in terms of both mechanical/contractile performance and electrical stability. The modification of the underlying myocardial physiology is complex, varying across the different layers within the wall of the ventricle and within one layer.

Short term exposure to elevated trinitrotoluene concentrations induced structural and functional changes in the soil bacterial community.

We investigated the acute impact of trinitrotoluene (TNT) contamination of soil on the aerobic bacterial community composition and function. The contamination of the environment with explosive residues presents a serious problem at sites across the world, with the highly toxic compound TNT being the most widespread explosive contaminant. We investigated the acute impact of trinitrotoluene (TNT) contamination of soil on the aerobic bacterial community composition and function.