Differential sensitivity of Ca²+ wave and Ca²+ spark events to ruthenium red in isolated permeabilised rabbit cardiomyocytes.

Spontaneous Ca²(+) waves in cardiac muscle cells are thought to arise from the sequential firing of local Ca²(+) sparks via a fire-diffuse-fire mechanism. This study compares the ability of the ryanodine receptor (RyR) blocker ruthenium red (RuR) to inhibit these two types of Ca²(+) release in permeabilised rabbit ventricular cardiomyocytes. Perfusing with 600 nm Ca²(+) (50 μm EGTA) caused regular spontaneous Ca²(+) waves that were imaged with the fluorescence from Fluo-5F using a laser-scanning confocal microscope.

Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery.

High-intensity exercise training contributes to the production and accumulation of blood lactate, which is cleared by active recovery. However, there is no commonly agreed intensity or mode for clearing accumulated blood lactate. We studied clearance of accumulated blood lactate during recovery at various exercise intensities at or below the lactate threshold after high-intensity interval runs that prompted lactate accumulation.

Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium.

One of the main outcomes of aerobic endurance exercise training is the improved maximal oxygen uptake, and this is pivotal to the improved work capacity that follows the exercise training. Improved maximal oxygen uptake in turn is at least partly achieved because exercise training increases the ability of the myocardium to produce a greater cardiac output. In healthy subjects, this has been demonstrated repeatedly over many decades.

An ancient anion-binding structural module in RNA and DNA helicases.

RNA and DNA helicases manipulate or translocate along single strands of nucleic acids by grasping them using a conserved structural motif. We have examined the available crystal structures of helicases of the two principal superfamilies, SF1 and SF2, and observed that the most conserved interactions with the nucleic acid occur between the phosphosugar backbone of a trinucleotide and the three strand-helix loops within a (beta-strand/alpha-helix)(3) structural module. At the first and third loops is a conserved hydrogen-bonded feature called a thr-motif, often seen at alpha-helical N-termini, with the threonine as the N-cap residue.

Uptake of purines in Plasmodium falciparum-infected human erythrocytes is mostly mediated by the human equilibrative nucleoside transporter and the human facilitative nucleobase transporter.

Background: Plasmodium parasites are unable to synthesize purines de novo and have to salvage them from the host. Due to this limitation in the parasite, purine transporters have been an area of focus in the search for anti-malarial drugs. Although the uptake of purines through the human equilibrative nucleoside transporter (hENT1), the human facilitative nucleobase transporter (hFNT1) and the parasite-induced new permeation pathway (NPP) has been studied, no information appears to exist on the relative contribution of these three transporters to the uptake of adenosine and hypoxanthine.

Software for quantifying and simulating microsatellite genotyping error.

Microsatellite genetic marker data are exploited in a variety of fields, including forensics, gene mapping, kinship inference and population genetics. In all of these fields, inference can be thwarted by failure to quantify and account for data errors, and kinship inference in particular can benefit from separating errors into two distinct classes: allelic dropout and false alleles. Pedant is MS Windows software for estimating locus-specific maximum likelihood rates of these two classes of error.

Fate specification and tissue-specific cell cycle control of the Caenorhabditis elegans intestine.

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein beta-transducin repeat-containing protein (beta-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans beta-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.

High-intensity aerobic exercise training improves the heart in health and disease.

Regular exercise training confers beneficial effects to the heart as well as to the entire body. This occurs partly because exercise training improves skeletal muscle work capacity and reduces resistance, thus increasing conductance in the peripheral circulation. More directly, exercise training also alters extrinsic modulation of the heart and improves the intrinsic pump capacity of the heart.

Efficient liver-directed gene transfer by in situ generation of retroviral vector from adenoviral templates.

Unlabelled: To improve liver-directed retroviral-mediated gene transfer, we injected C57/BL10 mice intravenously with three adenoviral vectors encoding retroviral vector genome and structural components: AdGagPol expressing the respective structural genes of Moloney murine leukaemia virus, Ad10A1Env expressing the 10A1 envelope protein of 10A1-MuLV, and AdLEIN, encoding the LEIN retrovirus genome, expressing green fluorescence protein (eGFP) and the neomycin resistance gene.

Materials And Methods: The extent of eGFP expression was determined after 1 and 15 weeks by fluorescence microscopy and FACS analysis. Proviral integration was determined by a novel PCR-based technique.

Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow outcome score.

Magnetic resonance imaging provides evidence for loss of both white and grey matter, in terms of tissue volume, from the cerebral hemispheres after traumatic brain injury. However, quantitative histopathological data are lacking. From the archive of the Department of Neuropathology at Glasgow, the cerebral cortex of 48 patients was investigated using stereology.

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis.

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca).

Genotypic status of the TbAT1/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal.

Background: The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T. brucei adenosine transporter 1 gene (TbAT1). Previously, specific TbAT1 mutant type alleles linked to melarsoprol treatment failure were significantly more prevalent in T.

Cloning and expression of activation induced cytidine deaminase from Bos taurus.

Activation induced cytidine deaminase is an enzyme crucial to somatic hypermutation and gene conversion, processes that are essential for the diversification of Ig V genes. The bovine Ig repertoire appears to be diversified by mechanisms that are significantly different to those that operate in humans and mice. This study set out to test the hypothesis that differences in the organization, coding sequence, expression or genomic location of the bovine AICDA gene enables the encoded enzyme to catalyse the unusual Ig diversification mechanism seen in cattle as well as conventional antigen-driven mutation.

Detection of artemisinin-resistant Plasmodium falciparum in malarial infection: a brief review of methods.

The WHO has recommended artemisinin-based combination therapy (ACT) for the treatment of malaria in disease endemic countries. In an attempt to assess the sensitivity of Plasmodium falciparum to the drug, various methods have been used. It is the purpose of this short review to critically examine these methods and give recommendations.

Schistosoma mansoni cercariae experience influx of macromolecules during skin penetration.

We have observed that when cercariae penetrate the skin of mice, there is influx into their tissues of Lucifer Yellow and certain labelled molecules of up to 20 kDa molecular weight. This observation was made using a variety of fluorescent membrane-impermeant compounds injected into the skin before the application of cercariae. This unexpected phenomenon was investigated further by transforming cercariae in vitro in the presence of the membrane-impermeant compounds and examining the distribution by microscopy.

Adenosine receptors and neurological disease: neuroprotection and neurodegeneration.

Adenosine receptors modulate neuronal and synaptic function in a range of ways that may make them relevant to the occurrence, development and treatment of brain ischemic damage and degenerative disorders. A(1) adenosine receptors tend to suppress neural activity by a predominantly presynaptic action, while A(2A) adenosine receptors are more likely to promote transmitter release and postsynaptic depolarization. A variety of interactions have also been described in which adenosine A(1) or A(2) adenosine receptors can modify cellular responses to conventional neurotransmitters or receptor agonists such as glutamate, NMDA, nitric oxide and P2 purine receptors.

The schistosome excretory system: a key to regulation of metabolism, drug excretion and host interaction.

There is a gulf between the enormous information content of the various genome projects and the understanding of the life of the parasite in the host. In vitro studies with adult Schistosoma mansoni using several substrates suggest that the excretory system contains both P-glycoproteins and multiresistance proteins. If both these families of protein were active in vivo, they could regulate parasite metabolism and be responsible for the excretion of drugs.

The effect of progesterone on myometrial contractility, potassium channels, and tocolytic efficacy.

Objectives: Recent clinical trials have demonstrated a beneficial effect of supplementation with progesterone to prevent preterm labor. We aimed to determine the effects of progesterone treatment in vitro and in vivo and 17alpha-hydroxyprogesterone caproate (17OHPC) in vitro on myometrial contractions.

Methods: Myometrial strips were taken from women undergoing cesarean delivery at term.

Cellular and molecular basis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is caused by functional and structural changes in the pulmonary vasculature, leading to increased pulmonary vascular resistance. The process of pulmonary vascular remodeling is accompanied by endothelial dysfunction, activation of fibroblasts and smooth muscle cells, crosstalk between cells within the vascular wall, and recruitment of circulating progenitor cells. Recent findings have reestablished the role of chronic vasoconstriction in the remodeling process.

Whole proteome analysis of osteoprogenitor differentiation induced by disordered nanotopography and mediated by ERK signalling.

Topographic features can modulate cell behaviours such as proliferation, migration, differentiation and apoptosis. Biochemical mechanotransduction implies the conversion of mechanical forces (e.g.

The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+ enriched skeletal stem cells.

The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways.

Adeno-associated virus-8-mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle.

Myostatin is a member of the transformating growth factor-beta (TGF-beta) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a 'double muscling' phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia.

The Toxoplasma gondii plastid replication and repair enzyme complex, PREX.

A plastid-like organelle, the apicoplast, is essential to the majority of medically and veterinary important apicomplexan protozoa including Toxoplasma gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome, the replication of which is dependent upon nuclear-encoded proteins that are imported into the organelle. In P.

5-Hydroxyanthranilic acid, a tryptophan metabolite, generates oxidative stress and neuronal death via p38 activation in cultured cerebellar granule neurones.

The essential amino acid tryptophan is primarily metabolised through the kynurenine pathway, some components of which may be neurotoxic. We have now examined the potential toxicity of several kynurenine metabolites in relation to the generation of oxidative stress and activation of cell death signalling pathways in cultured cerebellar granule neurons. 3-Hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and 5-hydroxyanthranilic acid (5HAA) induced cell death which increased with exposure time and compound concentration.

The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes.

This study examines the effects of the intracellular protein FKBP12.6 on action potential and associated K(+) currents in isolated adult rabbit ventricular cardiomyocytes. FKBP12.