Bridge percolation: electrical connectivity of discontinued conducting slabs by metallic nanowires.

The properties of nanostructured networks of conductive materials have been extensively studied under the lens of percolation theory. In this work, we introduce a novel type of local percolation phenomenon used to investigate the conduction properties of a new hybrid material that combines sparse metallic nanowire networks and fractured conducting thin films on flexible substrates. This original concept could potentially lead to the design of a novel composite transparent conducting material. Using a complementary approach including formal analytical derivations, Monte Carlo simulations and electrical circuit representation for the modelling of bridged-percolating nanowire networks, we unveil the key relations between linear crack density, nanowire length and network areal mass density that ensure electrical percolation through the hybrid. The proposed theoretical model provides key insights into the conduction mechanism associated with the original concept of bridge percolation in random nanowire networks.

Optimization of silver nanowire-based transparent electrodes: effects of density, size and thermal annealing.

Silver nanowire (AgNW) networks are efficient as flexible transparent electrodes, and are cheaper to fabricate than ITO (Indium Tin Oxide). Hence they are a serious competitor as an alternative to ITO in many applications such as solar cells, OLEDs, transparent heaters. Electrical and optical properties of AgNW networks deposited on glass are investigated in this study and an efficient method to optimize them is proposed. This paper relates network density, nanowire dimensions and thermal annealing directly to the physical properties of the nanowire networksusing original physical models. A fair agreement is found between experimental data and the proposed models. Moreover thermal stability of the nanowires is a key issue in thermal optimization of such networks and needs to be studied. In this work the impact of these four parameters on the networks physical properties are thoroughly investigated via in situ measurements and modelling, such a method being also applicable to other metallic nanowire networks. We demonstrate that this approach enables the optimization of both optical and electrical properties through modification of the junction resistance by thermal annealing, and a suitable choice of nanowire dimensions and network density. This work reports excellent optical and electrical properties of electrodes fabricated from AgNW networks with a transmittance T = 89.2% (at 550 nm) and a sheet resistance of Rs = 2.9 Ω â–¡(-1), leading to the highest reported figure of merit.

Metallic nanowire networks: effects of thermal annealing on electrical resistance.

Metallic nanowire networks have huge potential in devices requiring transparent electrodes. This article describes how the electrical resistance of metal nanowire networks evolve under thermal annealing. Understanding the behavior of such films is crucial for the optimization of transparent electrodes which find many applications. An in-depth investigation of silver nanowire networks under different annealing conditions provides a case study demonstrating that several mechanisms, namely local sintering and desorption of organic residues, are responsible for the reduction of the systems electrical resistance. Optimization of the annealing led to specimens with transmittance of 90% (at 550 nm) and sheet resistance of 9.5 Ω sq(-1). Quantized steps in resistance were observed and a model is proposed which provides good agreement with the experimental results. In terms of thermal behavior, we demonstrate that there is a maximum thermal budget that these electrodes can tolerate due to spheroidization of the nanowires. This budget is determined by two main factors: the thermal loading and the wire diameter. This result enables the fabrication and optimization of transparent metal nanowire electrodes for solar cells, organic electronics and flexible displays.

Feasibility of an HA2 domain-based periodontitis vaccine.

In a rat periodontitis model, preinoculation with the Porphyromonas gingivalis HA2 binding domain for hemoglobin provided protection from disease. Protection was associated with induced anti-HA2 immunoglobulin G (IgG) humoral antibodies. The IgG subclass ratios suggested that relatively lower Th2/Th1-driven responses were directly associated with protection when rHA2 was administered in saline.

Impact of community neonatal services: a multicentre survey.

OBJECTIVES: To explore the impact of a community neonatal service on high risk infant survivors in the first year of life. DESIGN: Retrospective multicentre survey. Postal questionnaires were sent to selected parents. SETTING: Thirty two neonatal units in England and Wales. INCLUSION CRITERIA: infants over 12 months of age with birth weight < or =1500 g, or who received level I intensive care for at least 48 hours. EXCLUSION CRITERIA: multiple births, infants who had died or had severe congenital abnormalities. A total of 3367 eligible infants were selected, and their parents were sent a questionnaire; 65% responded. MAIN OUTCOME MEASURES: Length of stay on the neonatal unit from birth to initial discharge. Readmission to hospital during the first year of life. RESULTS: The median length of stay in units with a community neonatal service was 35 days compared with 37 days in units without. When adjusted for infant and parent characteristics, the median length of stay was reduced by 12.6% where a community neonatal service was provided (95% confidence interval 5.3% to 19.3%). The readmission rates were 44.6% in units with a community neonatal service and 43.5% in units without. There was no significant reduction in the adjusted odds of readmission. CONCLUSIONS: The retrospective nature of this study means that these findings cannot be definitely attributed to the presence of a community neonatal service. However, the results suggest that community neonatal services may reduce the length of stay without any subsequent increase in readmission.

Selective interactions of cationic porphyrins with G-quadruplex structures.

G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. Because G-quadruplex DNA exhibits structural polymorphism, different G-quadruplex typologies may be associated with different cellular processes. Therefore, to achieve therapeutic selectivity using G-quadruplexes as targets for drug design, it will be necessary to differentiate between different types of G-quadruplexes using G-quadruplex-interactive agents. In this study, we compare the interactions of three cationic porphyrins, TMPyP2, TMPyP3, and TMPyP4, with parallel and antiparallel types of G-quadruplexes using gel mobility shift experiments and a helicase assay. Gel mobility shift experiments indicate that TMPyP3 specifically promotes the formation of parallel G-quadruplex structures. A G-quadruplex helicase unwinding assay reveals that the three porphyrins vary dramatically in their abilities to prevent the unwinding of both the parallel tetrameric G-quadruplex and the antiparallel hairpin dimer G-quadruplex DNA by yeast Sgs1 helicase (Sgs1p). For the parallel G-quadruplex, TMPyP3 has the strongest inhibitory effect on Sgs1p, followed by TMPyP4, but the reverse is true for the antiparallel G-quadruplex. TMPyP2 does not appear to have any effect on the helicase-catalyzed unwinding of either type of G-quadruplex. Photocleavage experiments were carried out to investigate the binding modes of all three porphyrins with parallel G-quadruplexes. The results reveal that TMPyP3 and TMPyP4 appear to bind to parallel G-quadruplex structures through external stacking at the ends rather than through intercalation between the G-tetrads. Since intercalation between G-tetrads has been previously proposed as an alternative binding mode for TMPyP4 to G-quadruplexes, this mode of binding, versus that determined by a photocleavage assay described here (external stacking), was subjected to molecular dynamics calculations to identify the relative stabilities of the complexes and the factors that contribute to these differences. The DeltaG(o) for the external binding mode was found to be driven by DeltaH(o) with a small unfavorable TDeltaS(o) term. The DeltaG(o) for the intercalation binding model was driven by a large TDeltaS(o) term and complemented by a small DeltaH(o) term. One of the main stabilizing components of the external binding model is the energy of solvation, which favors the external model over the intercalation model by -67.94 kcal/mol. Finally, we propose that intercalative binding, although less favored than external binding, may occur, but because of the nature of the intercalative binding, it is invisible to the photocleavage assay. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by using structural variants within a single group of G-quadruplex-interactive drugs.

The Vancomycin biosynthetic pathway is induced in oxygen-limited Amycolatopsis orientalis (ATCC 19795) cultures that do not produce antibiotic.

Vancomycin biosynthetic capacity was stimulated in oxygen-limited bioreactor culture (6.4% DOT) of Amycolatopsis orientalis, coinciding with a down-regulation of the culture growth and protein synthesis rates. However no Vancomycin was detected. ATP production was similar in oxygen-limited and oxygen-sufficient cultures (400-150 µmole(ATP). g(biomass)(-1)). Our findings suggest a critical requirement for oxygen flux through the Vancomycin biosynthetic pathway, which is only met under nutrient-limited conditions in which oxygen is in excess.

Mechanism of inactivation of ornithine transcarbamoylase by Ndelta -(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism.

The crystal structure is reported at 1.8 A resolution of Escherichia coli ornithine transcarbamoylase in complex with the active derivative of phaseolotoxin from Pseudomonas syringae pv. phaseolicola, N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine. Electron density reveals that the complex is not a covalent adduct as previously thought. Kinetic data confirm that N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine exhibits reversible inhibition with a half-life in the order of approximately 22 h and a dissociation constant of K(D) = 1.6 x 10(-12) m at 37 degrees C and pH 8.0. Observed hydrogen bonding about the chiral tetrahedral phosphorus of the inhibitor is consistent only with the presence of the R enantiomer. A strong interaction is also observed between Arg(57) Nepsilon and the P-N-S bridging nitrogen indicating that imino tautomers of N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine are present in the bound state. An imino tautomer of N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine is structurally analogous to the proposed reaction transition state. Hence, we propose that N(delta)-(N'-sulfodiaminophosphinyl)-l-ornithine, with its three unique N-P bonds, represents a true transition state analogue for ornithine transcarbamoylases, consistent with the tight binding kinetics observed.

Eryloside F, a novel penasterol disaccharide possessing potent thrombin receptor antagonist activity.

We report the discovery of Eryloside F, a novel disaccharide of the steroidal carboxylic acid penasterol, isolated from an extract of the marine sponge Erylus formosus. The compound is a potent thrombin receptor antagonist, and furthermore inhibits human platelet aggregation in vitro.

Pyrimidine nucleotide-stimulated thromboxane A2 release from cultured glia.

1. Uridine triphosphate (UTP), uridine diphosphate (UDP), cytidine triphosphate (CTP), and deoxythymidine triphosphate (TTP) caused concentration-dependent increases in the release of thromboxane A2 (TXA2) from cultured glia prepared from the newborn rat cerebral cortex. Although each of the pyrimidine nucleotides displayed similar potencies, CTP and TTP were considerably less effective than either UTP or UDP. The purine nucleotide ATP was equally as potent as the pyrimidine nucleotides but was marginally less effective than either UTP or UDP. 2. The ability of UTP, UDP, TTP, and CTP to promote TXA2 release from cultured glia was inhibited in a concentration-dependent manner by suramin and was markedly reduced when incubations were performed either in Ca(2+)-free medium or on cultures which had been maintained in serum-free growth medium for 4 days prior to experimentation. 3. Challenges with UTP and UDP in combination were found to elicit a response which was no different from the effects of these nucleotides alone; in addition, their effects were reversed by the phospholipase A2 inhibitor ONO-RS-082. A slight reduction in UTP- and UDP-stimulated TXA2 release was observed in cultures grown in the presence of leucine methyl ester, a treatment reported to limit microglial survival. 4. These results suggest that glia are targets for extracellular pyrimidine nucleotides and that their ability to release eicosanoids from these cells may be important in the brain's response to damage.

Specialized distributions of mitochondria and endoplasmic reticulum proteins define Ca2+ wave amplification sites in cultured astrocytes.

This study was undertaken to examine the expression and role of the endoplasmic reticulum (ER) proteins calreticulin and ryanodine receptors, and mitochondria, in cultured astrocytes. Using several lines of investigation, we have identified a key role for mitochondria in astrocyte Ca2+ signalling: (1) a significant correlation was found between sites of regenerative Ca2+ wave amplification (possessing high amplitude ER Ca2+ release) and the location of mitochondria in the cell; (2) norepinephrine (2 microM) caused a rapid-onset increase in rhod 2 fluorescence in 34% of astrocyte mitochondria, indicating that cytosolic Ca2+ responses result in mitochondrial Ca2+ elevation; and (3) pretreatment with the protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone to inhibit mitochondrial activity markedly reduced the amplitude of subsequent norepinephrine-evoked cytosolic Ca2+ responses. We then investigated the roles of several ER proteins in Ca2+ signalling by immunocytochemistry. Ryanodine receptors and calreticulin were found to be expressed in heterogeneous patterns in astrocytes. The expression pattern of calreticulin corresponded closely with the distribution of mitochondria, whereas the expression of ryanodine receptors was not similar to that of either of these cellular factors. We measured Ca2+ wave kinetics in a single astrocyte, then assessed protein distribution by immunocytochemistry in the same cell. Cross-correlation between norepinephrine-evoked Ca2+ wave amplitude and calreticulin distribution indicated a close spatial relationship between this Ca2+-binding protein and sites of regenerative wave amplification. These results demonstrate that amplification sites for Ca2+ waves in astrocytes are identifiable by accumulations of calreticulin (and type 2 InsP3Rs), and by the presence of mitochondria, which may regulate the ER Ca2+ release process.

Characterization of ryanodine receptors in oligodendrocytes, type 2 astrocytes, and O-2A progenitors.

In this study we have investigated the expression of ryanodine receptors (RyRs), and the ability of caffeine to evoke RyR-mediated elevation of intracellular Ca2+ levels ([Ca2+]i) in glial cells of the oligodendrocyte/type 2 astrocyte lineage. Immunocytochemistry with specific antibodies identified ryanodine receptors in cultured oligodendrocytes, type 2 astrocytes, and O-2A progenitor cells, at high levels in the perinuclear region and in a variegated pattern along processes. Glia acutely isolated from rat brain and in aldehydefixed sections of cortex were similarly found to express RyRs. Caffeine (5-50 mM) caused an increase in [Ca2+]i in most cultured type 2 astrocytes and in 50% of oligodendrocytes. Responses elicited by caffeine were inhibited by pretreatment with ryanodine (10 microM) or thapsigargin (1 microM), and the peak response was unaffected by removal of [Ca2+]o. O-2A progenitor cells, in contrast, were largely unresponsive to caffeine treatment. Pretreatment with kainate (200 microM) to activate Ca2+ entry increased the magnitude of caffeine-evoked [Ca2+]i elevations in type 2 astrocytes and oligodendrocytes, and caused caffeine to activate responses in a significant proportion of previously non-responding O-2A progenitors. In both type 2 astrocytes and oligodendrocytes, caffeine evoked Ca2+ changes which propagated as wavefronts from several initiation sites. These wave amplification sites were characterized by significantly higher local Ca2+ release kinetics. Our results indicate that several glial cell types express RyRs, and that their functionality differs within different cell types of the oligodendrocyte lineage. In addition, ionotropic glutamate receptor activation fills the caffeine-sensitive Ca2+ stores in these cells.

Molecular dynamic simulations of environment and sequence dependent DNA conformations: the development of the BMS nucleic acid force field and comparison with experimental results.

Molecular dynamic (MD) simulations using the BMS nucleic acid force field produce environment and sequence dependent DNA conformations that closely mimic experimentally derived structures. The parameters were initially developed to reproduce the potential energy surface, as defined by quantum mechanics, for a set of small molecules that can be used as the building blocks for nucleic acid macromolecules (dimethyl phosphate, cyclopentane, tetrahydrofuran, etc.). Then the dihedral parameters were fine tuned using a series of condensed phase MD simulations of DNA and RNA (in zero added salt, 4M NaCl, and 75% ethanol solutions). In the tuning process the free energy surface for each dihedral was derived from the MD ensemble and fitted to the conformational distributions and populations observed in 87 A- and B-DNA x-ray and 17 B-DNA NMR structures. Over 41 nanoseconds of MD simulations are presented which demonstrate that the force field is capable of producing stable trajectories, in the correct environments, of A-DNA, double stranded A-form RNA, B-DNA, Z-DNA, and a netropsin-DNA complex that closely reproduce the experimentally determined and/or canonical DNA conformations. Frequently the MD averaged structure is closer to the experimentally determined structure than to the canonical DNA conformation. MD simulations of A- to B- and B- to A-DNA transitions are also shown. A-DNA simulations in a low salt environment cleanly convert into the B-DNA conformation and converge into the RMS space sampled by a low salt simulation of the same sequence starting from B-DNA. In MD simulations using the BMS force field the B-form of d(GGGCCC)2 in a 75% ethanol solution converts into the A-form. Using the same methodology, parameters, and conditions the A-form of d(AAATTT)2 correctly converts into the B-DNA conformation. These studies demonstrate that the force field is capable of reproducing both environment and sequence dependent DNA structures. The 41 nanoseconds (nsec) of MD simulations presented in this paper paint a global picture which suggests that the DNA structures observed in low salt solutions are largely due to the favorable internal energy brought about by the nearly uniform screening of the DNA electrostatics. While the conformations sampled in high salt or mixed solvent environments occur from selective and asymmetric screening of the phosphate groups and DNA grooves, respectively, brought about by sequence induced ion and solvent packing.

Generalized tertiary rainbow of slightly oblate drops: observations with laser illumination.

The tertiary rainbow of acoustically levitated water drops was observed in the laboratory. Nontrivial caustics were observed for relatively small values of eccentricity. The angular locations of caustics were modeled with matrix methods of generalized ray tracing. Photographs of the scattering were in general agreement with models. Possible effects on the appearance of natural tertiary bow features are discussed.

Exploring practical knowledge: a case study of an experienced senior tennis performer.

The purpose of the study was to explore sport-related practical knowledge through the perceptions and experiences of a senior adult competitive tennis performer. Practical knowledge was defined as goal oriented, experiential knowledge developed within particular physical activity settings. Data were collected through formal interviews and participant observation and analyzed through narrative inquiry and conventional coding techniques. The data suggest that the tennis environment was perceived in terms of the opportunities afforded by that environment. Specifically, the participant's practical knowledge centered on performance capabilities and strategic planning that revealed opponent limitations. This knowledge appeared to be developed and expressed within the relationships among individual capabilities, the task, and the situated context of game play.

The Bacillus subtilis DNA replication terminator.

The recent discovery of the Bacillus subtilis plasmid terminator TerLS20 with bidirectional fork arrest activity has provided the opportunity to probe further the structural and functional features of B. subtilis replication terminators in general. The minimal TerI and TerLS20 terminators each comprise two 13 nt segments flanking a central trinucleotide, which is almost completely conserved in all terminators. It corresponds to the region of overlap of the two RTP binding sites (A and B) on the DNA. It has been shown that, despite this conservation, considerable variation in this trinucleotide region still allows fork arrest activity. Thus, the productive interaction of the RTP dimers, which presumably occurs in the vicinity of this trinucleotide region, is not dependent upon stringently defined contacts with the bases in this region. A completely synthetic and highly symmetrical terminator was constructed by replacing the 13 nt segment of the A site of TerI with an opposed segment identical to that in the B site. The efficient bidirectional activity of this new terminator, TerSymB, established more firmly the need for two opposed RTP binding sites in a functional terminator. TerSymB was used to investigate the effect of sequence deviation in one of the 13 nt segments, from that in the B site, on bidirectionality of the terminator. It was found that the deviations introduced converted the terminator significantly towards polarity of action. The partial symmetry within each of the 13 nt segments of TerSymB, and the presumed recognition of this symmetry in the binding of a symmetrical dimer of RTP to each overlapping site, suggest that the bound dimers are centred over positions in the DNA sequence separated by 15 nt. This separation distance has been used in conjunction with the mode of binding of RTP to DNA proposed by Bussiere et al., based on their crystal structure for RTP, to model the interaction of the two dimers of RTP with unbent B-form DNA. Increased separation of the two binding sites of TerSymB was performed by inserting an extra three, seven or ten nucleotides centrally within the TerSymB sequence. The effects of these insertions on RTP binding and fork arrest activity were consistent with the proposed positioning of the RTP dimers within the terminator sequence, and interaction between the dimers bound to TerSymB. A model to account for the generation of RTP-terminator complexes with bidirectional or polar fork arrest activity utilising TerSymB or TerI-VI is presented.

Purine- and pyrimidine nucleotide-stimulated changes in intracellular calcium concentration in cultured astrocytes.

Cultured astrocytes prepared from the newborn rat cerebral cortex were challenged with a variety of purine and pyrimidine nucleotides and changes in intracellular Ca2+ concentration ([Ca2+]i) assessed. ATP, ADP, 2-methylthioadenosine triphosphate (2-MeSATP) and the pyrimidine nucleotide uridine triphosphate (UTP) produced Ca2+ transients which were characterized by an initial spike which decayed rapidly to a secondary plateau phase. Concentration response curves for these ligands gave the following rank order of potency: 2-MeSATP > ADP > ATP > UTP. Analysis of the number of cells responding to these nucleotides revealed that 2-MeSATP, ATP and ADP were effective in all cell fields examined whilst UTP generated a response in only 40%. In some experiments cells were challenged with various combinations of agonists. In those fields where ATP, 2-MeSATP and UTP were effective, the transients elicited by combined additions of these agonists were essentially the same as those produced by the agonists alone. Of the other nucleotides tested, uridine diphosphate was effective in only 24% of cell fields examined, moreover, its transient appeared to lack an initial spike phase. Guanosine triphosphate (GTP), cytidine triphosphate (CTP) and deoxythymidine triphosphate (TTP) were found to increase [Ca2+]i in 75%, 47% and 37% of cell fields respectively and the transients generated appeared to lack a secondary plateau phase. The responses to GTP, CTP and TTP also displayed rapid desensitization, a situation never encountered with ligands such as ATP.

Effects of CGS 9343B (a putative calmodulin antagonist) on isolated skeletal muscle. Dissociation of signaling pathways for insulin-mediated activation of glycogen synthase and hexose transport.

The role of calmoudulin in control of carbohydrate metabolism in the absence and presence of insulin in isolated mouse soleus muscle was investigated. The calmodulin antagonist CGS 9343B had no effect on basal glycogen synthase activity, the contents of high energy phosphates, glucose-6-P, or glycogen synthesis. However, CGS 9343B inhibited the basal rates of 2-deoxyglucose uptake and 3-O-methylglucose transport by 30% (p < 0.05) and 40% (p < 0.001), respectively. Insulin activated glycogen synthase by almost 40% (p < 0.01) and this increase was not altered in the presence of CGS 9343B. Insulin increased the muscle content of glucose-6-P (approximately equal to 2-fold), as well as glycogen synthesis (approximately equal to 8-fold), 2-deoxyglucose uptake (approximately equal to 3-fold), and 3-O-methylglucose transport (approximately equal to 2-fold), and these increases were inhibited by CGS 9343B. In additional experiments on isolated rat epitrochlearis muscle, it was found that the hypoxia-mediated activation of 3-O-methylglucose transport was also inhibited by CGS 9343B. These data demonstrate that: 1) hexose transport, both in the absence and presence of external stimuli (insulin and hypoxia), requires functional calmodulin; and 2) insulin-mediated activation of glycogen synthase does not require functional calmodulin, nor can it be accounted for by increases in glucose transport or glucose-6-P.

Examining the personal experience of student skill learning: a narrative perspective.

Examining the meaning of student skill learning from the learner's perspective is a valued but understudied topic in physical education. This paper investigated the learner's perspective as a storied experience and used narrative theory to interpret the meanings students derived from their learning experiences. Four narrative accounts were presented involving university students enrolled in a beginning level bowling class. The narratives centered on describing student goals and the conflicts and resolution of conflicts experienced by these students during skill learning. Two sources of generating meaning from experience were delineated: (a) an individual's active construction of meaning and (b) the enculturing influence of the social context. These narratives provided an opportunity for teachers and researchers to examine the realities constructed by students as a result of their learning experiences.

Purine- and pyrimidine-stimulated phosphoinositide breakdown and intracellular calcium mobilisation in astrocytes.

Phosphoinositide breakdown in cultured cortical astrocytes was assessed by measuring the accumulation of [3H]inositol phosphates (IP's) following incubations with various purines and pyrimidines. Dose-response relationships gave the following order of potency: 2-methylthioadenosine triphosphate (2-MeSATP) > uridine 5'-triphosphate (UTP) > ATP = ADP > inosine 5' triphosphate (ITP). However, 2-MeSATP and UTP were only half as effective as either ATP or ADP in stimulating [3H]IP production. Astrocytes were also challenged with combined additions of maximally effective concentrations of agonists. Responses to ADP plus UTP and 2-MeSATP plus UTP were essentially additive whilst ATP plus UTP evoked a response which was only partially additive. ATP-stimulated [3H]IP accumulation was markedly reduced in the presence of 2-MeSATP suggesting that the latter may be a partial agonist at these receptors. We also examined the ability of ATP and UTP to increase intracellular Ca2+ concentrations in these cells. Greater than 90% of all cells tested responded to ATP with a release from internal Ca2+ stores but less than half of these responded similarly when challenged with UTP. Our results indicate that astrocytes possess both P2Y-purinoceptors and a population of receptors which are also coupled to phosphoinositide metabolism and intracellular Ca2+ mobilisation but recognise ATP and the pyrimidine nucleotide UTP.