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The Lc petunia system, which displays enhanced, light-induced vegetative pigmentation, was used to investigate how high light affects anthocyanin biosynthesis, and to assess the effects of anthocyanin pigmentation upon photosynthesis. Lc petunia plants displayed intense purple anthocyanin pigmentation throughout the leaves and stems when grown under high-light conditions, yet remain acyanic when grown under shade conditions. The coloured phenotypes matched with an accumulation of anthocyanins and flavonols, as well as the activation of the early and late flavonoid biosynthetic genes required for flavonol and anthocyanin production. Pigmentation in Lc petunia only occurred under conditions which normally induce a modest amount of anthocyanin to accumulate in wild-type Mitchell petunia [Petunia axillaris x (Petunia axillaris x Petunia hybrida cv. 'Rose of Heaven')]. Anthocyanin pigmentation in Lc petunia leaves appears to screen underlying photosynthetic tissues, increasing light saturation and light compensation points, without reducing the maximal photosynthetic assimilation rate (A(max)). In the Lc petunia system, where the bHLH factor Leaf colour is constitutively expressed, expression of the bHLH (Lc) and WD40 (An11) components of the anthocyanin regulatory system were not limited, suggesting that the high-light-induced anthocyanin pigmentation is regulated by endogenous MYB transcription factors.

In this review we will discuss three main areas of research in plant–parasitic plant interactions. In the first section, we will deal with the physiology and biochemistry of the plant parasitic interaction, primarily focusing on the effects of resource abstraction. A functional split shall be introduced between parasites that are either predominantly xylem- or predominantly phloem feeding, and the implications of these two parasitic strategies discussed. In the second section we shall discuss the events leading up to the mature system, and the defenses employed by host plants against parasites. This section will focus on parasites’ life cycles, and on the hosts’ defense mechanisms against parasitism. Host plants and parasites are locked in a perpetual evolutionary arms race, with host plants evolving defenses, and parasites evolving counter-defense mechanisms. Significant events, such as parasite germination, and its subsequent attachment (or not) are discussed in reference to the functional groups introduced earlier. Finally, we discuss the evolution of parasitic plants and their ecological effects, from the negative effects of parasitic plants on agro-ecosystems, to their positive effects on plant biodiversity, via the suppression of dominant species, in natural and seminatural ecosystems.

Ring-current maps give an immediate visualisation of aromaticity on the magnetic criterion-by which a cyclic system that supports diatropic (paratropic) current induced by a perpendicular magnetic field is aromatic (anti-aromatic). Calculations of maps with the ipsocentric choice of origin are made in the 6-31G** basis set at Hartree-Fock (HF) and density functional (DFT) levels (PW91 and B3LYP functionals) on porphyrin, porphycene, orangarin, sapphyrin and hexabenzocoronene. In these systems, DFT and HF approaches produce optimal geometries with different point-group symmetries and/or different patterns of bond alternation. The ring-current maps derived with all four combinations of methods indicate that the main features of the current (global nature, direction, estimated strength) survive in systems with symmetry-breaking, but that choice of geometry is more critical for the detail of the current than is the electronic-structure method.

Potassic volcanics and intrusives of Eocene age (52±1 Ma) in the Highwood Mountains of north-central Montana provide evidence for interaction of asthenospheric magmas with Archean mantle lithosphere of the Wyoming Craton. Diverse rock types were produced by shallow level degassing, fractional crystallization and magma mixing within two separate magma series whose parental liquids were latite and olivine minette. Halogen systematics of apatite microphenocrysts and other evidence have established that shallow degassing of the phlogopite-diopside-phyric minettes to yield heteromorphic leucite-salite-phyric mafic phonolites and shonkinites was an important process. Geochemical and mineralogical data suggest that fractional crystallization of olivine, clinopyroxene, mica and leucite, accompanied by widespread magma mixing, produced a spectrum of more evolved magmas such as leucite phonolites, malignites, alkali syenites and trachytes along with mica clinopyroxenite cumulates. Sr, Nd and Pb isotopic compositions and trace element data for the primitive olivine minette magmas are explicable by a multistage model involving three source components. One component is ancient Ba-LREE-enriched, U-Th-HFSE-depleted subcontinental lithospheric mantle, which has been recognized in other alkalic rocks of the region, including those from the Crazy Mountains and Smoky Butte. Glimmerite-veined harzburgite and phlogopite dunite xenoliths (one with -eNd of −33 at 52 Ma) found in the most primitive Highwood olivine minette are probably samples of this material. The other two components are asthenospheric mantle with isotopic composition near that of bulk earth (and dominant in Montana alnoitic diatremes) and a young subduction-related component (probably Eocene, but possibly as old as late Cretaceous), which is required to explain the Rb/Sr-87Sr/86Sr systematics of the Highwood rocks. A consistent model for the petrogenesis of the Highwood parental mafic magmas involves partial melting of asthenospheric mantle wedge triggered by infiltration of melts released from the metasomatized carapace above a low-angle subducted slab of Farallon Plate lithosphere, followed by assimilative interaction of these melts with ancient, phlogopite-rich, metasome veins upon ascent through the Wyoming Craton mantle keel.

The response decay data of living cells subject to electric polarization is associated with their relaxation distribution function (RDF) and can be determined using the inverse Laplace transform method. A new polynomial, involving a series of associated Laguerre polynomials, has been used as the approximating function for evaluating the RDF, with the advantage of avoiding the usual arbitrary trial values of a particular parameter in the numerical computations. Some numerical examples are given, followed by an application to cervical tissue. It is found that the average relaxation time and the peak amplitude of the RDF exhibit higher values for tumorous cells than normal cells and might be used as parameters to differentiate them and their associated tissues.

Temporomandibular disorder pain dysfunction syndrome (TDPDS) is the most common cause of facial pain after toothache. The symptoms are varied but are likely to affect the choice, intake and enjoyment of food. This has not been previously investigated. In this paper a preliminary study of 35 patients attending a department of oral and maxillofacial surgery at a general hospital is presented. Thirty-one subjects reported that eating was a problem; 15 prepared food differently and 24 considered that their choice of food was limited. Four of the five foods most often reported to be difficult to eat are valuable in the diet: meat (22), apples (20), bread (13), toast (7) and toffees (6). Twenty-three subjects reported eating a softer diet. Most (25) reported pain when eating. Such circumstances make it harder for TDPDS sufferers to meet current nutritional guidelines, especially, perhaps, for some to achieve an adequate intake of iron.

Background 5-Hydroxytryptamine 3 (5-HT 3 ) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT 3B subunit on expression and signalling properties of heteromeric 5-HT 3AB receptors. Methods and results 5-HT 3AB receptor signalling was studied in a fluorescence-based cell membrane potential assay and by electrophysiology. Expression levels of cotransfected epitope-tagged 5-HT 3A and 5-HT 3B subunits were determined using enzyme-linked immunosorbent assay and immunocytochemistry. In cells coexpressing 5-HT 3A and 5-HT 3B (I143T) subunits, cell surface expression levels of 5-HT 3B in particular, and also 5-HT 3A were markedly reduced compared with those of wild-type (WT) 5-HT 3AB receptor-expressing cells. Electrophysiological recordings on cells coexpressing 5-HT 3A and 5-HT 3B (I143T) indicated cell surface expression of 5-HT 3AB (I143T) receptors with macroscopic current kinetics similar to those of WT 5-HT 3AB receptors but with 3-fold lower current densities. In the membrane potential assay, 5-HT 3AB (I143T)-transfected cells exhibited signalling properties intermediate to those of WT 5-HT 3AB and 5-HT 3A receptors. Cotransfection of 5-HT 3A , 5-HT 3AB (I143T) and WT 5-HT 3AB subunit cDNAs did not increase cell surface expression of the variant subunit nor did it restore WT 5-HT 3AB receptor signalling completely in the membrane potential assay. In contrast to 5-HT 3B (I143T), the 5-HT 3B variants S156R, V183I and A223T did not give rise to significant changes in 5-HT 3AB receptor expression or signalling properties. Conclusion 5-HT 3B (I143T)-containing 5-HT 3AB receptors display significantly reduced cell surface expression and different signalling properties compared with WT 5-HT 3AB receptors. In contrast, three other 5-HT 3B variants, S156R, V183I and A223T, do not appear to alter 5-HT 3AB receptor expression or signalling.

The aim of this study was to investigate the performance of awake fibreoptic intubation using remifentanil sedation with topical anaesthesia limited only to the nasal mucosa. Twenty-four patients presenting for elective head and neck surgery were sedated using remifentanil titrated to effect and local anaesthetic was applied to the nasal mucosa. Vital signs were recorded throughout the procedure and both the anaesthetist and an observer rated the ease of the procedure. Intubation was successful in all patients and the procedure was rated as easy in 15 (63%) of patients. Mean arterial pressure remained within 8% of baseline in all cases and respiratory rate remained > 8 breaths.min(-1) in all but three patients. Although 56% of patients interviewed postoperatively said they recalled the procedure, all but one would undertake the same procedure again if necessary. This technique appears reliable in providing adequate sedation whilst maintaining cardiovascular and respiratory stability.

Adenosine is an endogenous inhibitor of excitatory synaptic transmission with potent anticonvulsant properties in the mammalian brain. Given adenosine's important role in modulating synaptic transmission, several mechanisms exist to regulate its extracellular availability. One of these is the intracellular enzyme adenosine kinase (ADK), which phosphorylates adenosine to AMP. We have investigated the role that ADK plays in regulating the presence and effects of extracellular adenosine in area CA1 of rat hippocampal slices. Inhibition of ADK activity with 5'-iodotubercidin (IODO; 5 mu M) raised extracellular adenosine, as measured with adenosine biosensors, and potently inhibited field excitatory post-synaptic 2 potentials (fEPSPs) in an adenosine A(1)R-dependent manner. In nominally Mg2+-free aCSF, which facilitated the induction of electrically-evoked epileptiform activity, adenosine biosensor recordings revealed that seizures were accompanied by the transient release of adenosine. Under these conditions, IODO also inhibited the fEPSP and greatly suppressed epileptiform activity evoked by brief, high-frequency stimulation. During spontaneous seizures evoked by the AIR antagonist CPT, adenosine release was unaffected by IODO. This suggests that ADK activity does not limit activity-dependent adenosine release. On the basis of strong ADK immunoreactivity in GFAP-positive cells, astrocytes are likely to play a key role in regulating basal adenosine levels. It is this action of ADK on the basal adenosine tone that is permissive to seizure activity, and, by extension, other forms of activity-dependent neuronal activity such as synaptic plasticity. (c) 2008 Elsevier Ltd. All rights reserved.

Parasitism is well understood to have wide-ranging deleterious effects on host performance in species thus far characterized. Photosynthetic performance reductions have been noted in the Striga-Zea mays association; however, no such information exists for facultative hemiparasitic plants and their hosts, nor are the effects of host species understood.Chlorophyll fluorimetry was used to study the effects of parasitism by the hemiparasite Rhinanthus minor on the grass Phleum bertolinii and the forb Plantago lanceolata, and the effects of host species on the photosynthetic apparatus of R. minor.Parasitism by Rhinanthus led to a significant decrease in the host, and total (host + parasite) biomass in Phleum; however, in Plantago, no significant repression of growth was noted. Maximum quantum yield (F(v)/F(m)) was reduced in parasitized Plantago, relative to control plants, but not in Phleum. F(v)/F(m) was significantly lower in R. minor parasitizing Phleum than Plantago, suggesting Phleum to be a superior host to Plantago for R. minor. Steady-state quantum yield (Phi(PSII)) was significantly depressed in parasitized Phleum, but only at low irradiances in Plantago. Phi(PSII) was very low for R. minor grown on Plantago, but not Phleum.Shown here is the first evidence of the suppression of host photosynthesis by a facultative hemiparasitic plant, which has significant effects on total biomass production. Host identity is a significant factor in parasite success, with the forb Plantago lanceolata exhibiting apparent chemical as well as previously identified physical defences to parasitism. It is proposed that the electron transport rate (as denoted by Phi(PSII)) represents the limiting factor for biomass accumulation in this system, and that Plantago is able to suppress the growth of Rhinanthus by suppressing the electron transport rate.

The type 1 cannabinoid receptor (CB 1 receptor) is considered to be the most abundant G protein-coupled receptor (GPCR) in the mammalian brain. The presence and highly compartmentalized cellular distribution of CB 1 receptors in neurons localized to corticolimbic areas, basal ganglia, cerebellum, and brain- stem accounts for the majority of behavioral actions associated with cannabinoid drugs. The discovery of endocannabinoids led to an avalanche of data showing that signaling at this GPCR is critical for, e.g., neurogenesis, neural development, synaptic plasticity, learning and memory, food intake, and energy metabolism. In contrast, deficient CB 1 receptor expression or coupling to downstream signal transduction cascades contributes to the neuropathogenesis of a broad variety of neurological and metabolic disorders with selective pharmacological modula- tion of CB 1 receptor availability and activity being a prime target for therapeutic intervention. Here, we summarize contemporary knowledge on the regulation of CB 1 receptor expression in the central nervous system and describe the context- dependent recruitment of second messengers to this receptor. Finally, we present the concept that CB 1 receptor bioavailability together with its momentary sign- aling activity on neuronal membranes defines the efficacy of endocannabinoid signaling such that a fine-tuned control of synaptic efficacy and plasticity may be achieved.

Time-of-flight spectra of the nascent H atoms, and laser induced fluorescence excitation spectra of the nascent NH 2 radicals, are leading to a very complete knowledge of the energy disposal following photodissociation of NH 3 through its A 1 A 2 excited state. Both the dissociation rates and the product distributions are sensitive to the values of the vibrational and rotational quantum numbers of the quasi-bound levels of the parent molecule. The most populated fragment states involve the a-axis rotational, and bending vibrational, motions of the NH2 with modest excitation of further rotational degrees of freedom at low internal energy. For most NH 2 internal states the accompanying H atoms recoil close to the initial plane of NH 3 excitation, but for a specific subset of product states the H atoms recoil perpendicular to this plane. These measurements and their interpretation give a detailed insight into the intramolecular motion of the dissociating NH3 molecule, which is dynamically controlled but yet involves most of the internal degrees of freedom.

BASALTS, basaltic andesites and andesites in subduction-related magmatic arcs are all depleted in high-field-strength elements (such as Ti, V, Zr, Nb, Hf and Ta) relative to mid-ocean-ridge basalt (MORB). Here we show that these depletions can be produced in liquids by interaction with depleted mantle periodotite, as would occur during the ascent of an arc magma through the mantle lithosphere of the overriding plate. This process involves extensive reaction between liquid, olivine, orthopyroxene and spinel. High-field-strength element depletions are produced because olivine, orthopyroxene and spinel have higher crystal/liquid distribution coefficients for these elements than for other incompatible trace elements. Liquids modified by mantle–magma interaction will also be depleted in heavy rare-earth elements, Cr and Ni, and enriched in light rare-earth and large-ion lithophile elements, relative to MORB. These characteristics are all common in mafic magmas at convergent plate margins1–7.

Angrites are amongst the oldest basalts in the solar system and their origins are enigmatic, some even proposing the planet Mercury as the parent body (APB). Whatever their exact provenance their chronometry provides insights into early stages of planetary melting and differentiation. We present the first high-precision internal 182Hf- 182W isochrons for such early differentiated objects. Angrites Sahara 99555, D'Orbigny, and Northwest Africa 2999 define ages of 5.1 ± 1.3 Ma, 4.7 ± 1.3 Ma and 9.5 ± 3.3 Ma respectively after formation of calcium-aluminum-rich refractory inclusions (CAIs). These data are in good agreement with 26Al- 26Mg, 53Mn- 53Cr and most 207Pb- 206Pb ages for other angrites and provide evidence for two texturally and temporally well-resolved groups. The quenched angrites (SAH 99555, D'Orbigny and five others) have a weighted mean age of 4562.1 ± 0.4 Ma and are the products of igneous crystallization on the APB ∼ 5 Ma after the formation of CAIs, whereas the more slowly cooled angrites (NWA 2999, Angra dos Reis, LEW 86010, average age: 4557.7 ±0.2 Ma) reflect metamorphic closure ∼ 5 Ma later following second reheating process or a complex cooling history. The concordance obtained between various short-lived chronometers provides evidence that 26Al, 53Mn and 182Hf were homogeneously distributed in the solar nebula, although we cannot rule out the possibility of local small heterogeneities. Contrary to recent proposals, the data are also consistent with the previously determined age of the solar system based on 207Pb- 206Pb systematics of CAIs. The Hf-W data are discussed in the context of two endmember models for the early differentiation of the angrite parent body. In the first model, core formation occurred at 3-4 Ma after CAIs and both groups of angrites formed by two distinct partial melting events from the bulk mantle of the angrite parent body. In the second model, the angrite parent body underwent progressive core formation with an increasing degree of W-depletion over time. In this model, the two groups of angrites derive from distinct reservoirs. The heat sources responsible for such late melting and core formation are unclear. Quenched angrites are coeval with non-magmatic IAB iron meteorites and CB chondrules at ∼ 4562 Ma. However, demonstration of a genetic link between angrite melting and impact events must await the acquisition of still higher resolution chronometry. © 2007 Elsevier B.V. All rights reserved.

It is well documented that the hormone leptin regulates many central functions and that hippocampal CA1 pyramidal neurons are a key target for leptin action. Indeed, leptin modulates excitatory synaptic transmission and synaptic plasticity at the Schaffer-collateral input to CA1 neurons. However the impact of leptin on the direct temporoammonic (TA) input to CA1 neurons is not known. Here we show that leptin evokes a long-lasting increase [long-term potentiation (LTP)] in excitatory synaptic transmission at TA-CA1 synapses in rat juvenile hippocampus. Leptin-induced LTP was NMDA receptor-dependent and specifically involved the activation of GluN2B subunits. The signaling pathways underlying leptin-induced LTP involve the activation of phosphoinositide 3-kinase, but were independent of the ERK signaling cascade. Moreover, insertion of GluA2-lacking AMPA receptors was required for leptin-induced LTP as prior application of philanthotoxin prevented the effects of leptin. In addition, synaptic-induced LTP occluded the persistent increase in synaptic efficacy induced by leptin. In conclusion, these data indicate that leptin induces a novel form of NMDA receptor-dependent LTP at juvenile TA-CA1 synapses, which has important implications for the role of leptin in modulating hippocampal synaptic function in health and disease.

Monolithic integration of silicon micro-photonic devices with silicon microelectronics presents one potential solution to the interconnect bottleneck in deep submicron CMOS microprocessors. However, an inability to develop a robust silicon based electroluminescent (EL) technology continues to severely limit the feasibility of such a structure. Despite its promising photoluminescent (PL) properties, the erbium doped silicon rich silicon oxide material system has been only partly successful in EL devices owing to dielectric breakdown resulting from high field excitation requirements. However, PL data indicate that quantum confinement effects in this system enable it to overcome many of the luminescence quenching properties of bulk silicon based materials, while simultaneously offering the structural and chemical resilience which luminescent forms of silicon (eg. porous silicon) lack. However, it is now clear that the resolution of the current injection problem will require a detailed understanding of all known and especially potential luminescence excitation mechanisms. The present study compares PL measurements made for SiOx:Er (x less than or equal to 2) thin films grown by electron cyclotron resonance plasma enhanced chemical vapour deposition. Various compositions, containing erbium concentration below 1 atomic %, have been annealed over a range of temperatures between 600-1100 °C. The presence of excess silicon relative to SiO2 is found to result in a 100 fold increase of the PL emission near 1540 nm, resulting from the 4I13/2 to 4I15/2 transition of the trivalent erbium ion, relative to a sample containing no silicon excess. It has been found that luminescent silicon nano-clusters can be formed throughout the range of anneal temperatures studied. A dense array of extremely small amorphous silicon clusters is found to result in an optimized sensitization of the PL at 1540 nm for annealing at 800°C. It is proposed that in some cases, silicon nano-clusters coupled to erbium ions do not emit their intrinsic luminescence. Various oxygen-based luminescent defects are identified in this study, and they seem to exhibit a coupling to silicon nano-cluster and erbium-related centres. Possible application of these films to recently developed field-effect EL devices is discussed.

It is well documented that the hormone leptin plays a pivotal role in regulating food intake and body weight via its hypothalamic actions. However, leptin receptors are expressed throughout the brain with high levels found in the hippocampus. Evidence is accumulating that leptin has widespread actions on CNS function and in particular learning and memory. Recent studies have demonstrated that leptin-deficient or-insensitive rodents have impairments in hippocampal synaptic plasticity and in spatial memory tasks performed in the Morris water maze. Moreover, direct administration of leptin into the brain facilitates hippocampal long-term potentiation (LTP), and improves memory performance in mice. There is also evidence that, at the cellular level, leptin has the capacity to convert hippocampal short-term potentiation (STP) into LTP, via enhancing NMDA receptor function. Recent data indicates that leptin can also induce a novel form of NMDA receptor-dependent hippocampal long-term depression. Here, we review the evidence implicating a key role for the hormone leptin in modulating hippocampal synaptic plasticity and discuss the role of lipid signaling cascades in this process.

Summary • A simple, improved model of Rubisco synthesis and degradation in cereal leaves is developed using data obtained over the leaf lifespan to return maximum likelihood values for Rubisco proteolysis and biosynthesis. It assumes that the time course of leaf Rubisco content can be described using a log-normal curve, and degradation of the Rubisco pool occurs exponentially. • Curve parameters give an insight into how Rubisco dynamics differ among treatments or genotypes; also, statistical analyses can be performed more easily, requiring fewer data and allowing more flexibility in sampling than previous studies. • Predicted patterns of synthesis correlate well with independent rbc gene transcript data. Rubisco degradation is a first-order decay process, and biosynthesis correlates with leaf elongation rates. • As Rubisco degradation takes place according to first-order kinetics, control of leaf Rubisco concentration must be exerted by adjustment of biosynthetic, rather than proteolytic, rates.

The development of monolithically integrated optoelectronics in silicon has been hindered to date primarily because of silicon's inefficient optical emission properties. Recently, however, nanostructured systems exploiting quantum confinement effects have shown the potential to circumvent this problem. In this study, silicon-rich silicon oxide (SiO x , x

Phosphoinositide 3-kinase (PI3-kinase) has been shown to link leptin receptor activation to stimulation of large conductance Ca2+-activated K+ (BK) channels and subsequent inhibition of hippocampal epileptiform-like activity. However, the downstream targets of PI3-kinase in this action of leptin are unknown. Here we show that BK channel activation by leptin is dependent on the actin cytoskeleton, as it is prevented by actin filament stabilization and mimicked by actin disruption. Fluorescent labeling of polymerized actin filaments revealed that leptin promotes the rapid rearrangement of actin filaments via activation of PI 3-kinase; an action paralleled by discrete increases in PtdIns(3,4,5)P3 immunoreactivity in close proximity to BK channels. After leptin exposure, there was also an actin-dependent increase in the association of BK channel immunoreactivity with synaptic markers. These data are consistent with the notion that leptin activates BK channels via PI 3-kinase-dependent reorganization of actin filaments and subsequent clustering of BK channels at synapses.

Long-term depression (LTD) of excitatory synaptic transmission is a persistent weakening of synaptic strength that is involved in learning and memory processes and neuronal development (Bear & Abraham, 1996). Two main forms exist in the mammalian CNS, that are induced by the synaptic activation of N-methyl-D-aspartate (NMDA; Bear & Abraham, 1996) and metabotropic glutamate receptors (mGluRs; Anwyl, 1999; Kemp & Bashir, 2001), respectively. Homosynaptic NMDA receptor-dependent LTD is expressed postsynaptically and triggered by Ca2+ influx via NMDA channels and subsequent activation of serine/threonine protein phosphatases (Mulkey et al, 1993; 1994). In contrast, mGluR-dependent LTD is independent of Ca2+ (Fitzjohn et al, 2001) and serine/threonine phosphatases (Schnabel et al, 2001), and may have a presynaptic mechanism of expression (Rammes et al, 2003). Insulin can also induce LTD at hippocampal CA1 synapses (Huang et al, 2004), via activation of a phosphoinositide 3-kinase (PI 3-kinase)/PKC-linked pathway. The hormone leptin is best known for its role in regulating energy homeostasis via actions on specific hypothalamic nuclei (Ahima & Flier, 2000). However, leptin receptors are expressed in numerous brain regions (Elmquist et al, 1998; Shanley et al, 2002), suggesting that leptin has additional functions in the CNS. Indeed, leptin enhances NMDA receptor activity and modulates hippocampal LTP (Shanley et al, 2001). Obese rodents with dysfunctional leptin receptors also display impairments in hippocampal LTP and LTD (Li et al, 2002), and administration of leptin into the dentate gyrus enhances the level of LTP in vivo (Wayner et al, 2004), consistent with the notion that leptin modulates excitatory synaptic strength. However the effects of leptin on hippocampal LTD remain to be established. Leptin receptors are class I cytokine receptors that signal via association with janus tyrosine kinases (JAKs). Activated JAKs can stimulate various downstream signaling pathways, including PI 3-kinase. Indeed, PI 3-kinase is a key element of leptin receptor signaling in neurones (Shanley et al, 2001, 2002a,Shanley et al, b; Niswender et al, 2001). Another target for activated JAKs is the adaptor protein SHP-2, which initiates the Grb2-Ras-Raf MAPK (mitogen-activated protein kinase) signaling cascade. Stimulation of this pathway by leptin has also been observed in neurones (Shanley et al, 2001). Recent studies suggest that PI 3-kinase and MAPK play a prominent role in hippocampal synaptic plasticity. PI 3-kinase inhibitors block the induction (Opazo et al, 2003; Man et al, 2003) and maintenance of NMDA receptor-dependent LTP (Kelly & Lynch, 2000; Sanna et al, 2002). PI 3-kinase also regulates the synapse-specificity of homosynaptic LTD (Daw et al, 2002), and a PI 3-kinase-linked pathway is required for mGluR- (Hou & Klann, 2004) and insulin-induced LTD (Huang et al, 2004). Additionally, MAPK-dependent signaling pathways regulate the efficacy of excitatory synaptic transmission (Thomas & Huganir, 2004; Thiels et al, 2002), and hippocampal mGluR-dependent LTD (Gallagher et al, 2004). In this study we examined the effects of leptin on hippocampal excitatory synaptic transmission. We show that under conditions of enhanced excitability, leptin induces a long-lasting depression of excitatory synaptic transmission that is independent of MAPK, but modulated by PI 3-kinase and protein phosphatase activity.

Elevated glycogen synthase kinase-3 (GSK-3) activity is associated with Alzheimer disease. We have found that collapsin response mediator proteins (CRMP) 2 and 4 are physiological substrates of GSK-3. The amino acids targeted by GSK-3 comprise a hyperphosphorylated epitope first identified in plaques isolated from Alzheimer brain. Expression of wild type CRMP2 in primary hippocampal neurons or SH-SY5Y neuroblastoma cells promotes axon elongation. However, a GSK-3-insensitive CRMP2 mutant has dramatically reduced ability to promote axon elongation, a similar effect to pharmacological inhibition of GSK-3. Hence, we propose that phosphorylation of CRMP proteins by GSK-3 regulates axon elongation. This work provides a direct connection between hyperphosphorylation of these residues and elevated GSK-3 activity, both of which are observed in Alzheimer brain.

1. Group I metabotropic glutamate receptors (mGluRs) are thought to be important modulators of neuronal function in the superior colliculus (SC). Here, we investigated the pharmacology and signalling mechanisms underlying group I mGluR-mediated inhibition of neuronal excitability and synaptic transmission in the rat SC slice. 2. The group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potently depressed synaptically evoked excitatory postsynaptic potentials (EPSPs), currents (EPSCs), and action potentials in a dose-dependent manner (IC50: 6.3 microm). This was strongly reduced by the broad-spectrum antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mm, approximately 95% reduction), by the mGluR1 antagonist LY367385 (100 microm, approximately 80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 1-100 microm). 3. The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microm) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 microm) reduced the effect of CHPG by 50%. 4. Inhibition induced by DHPG was independent of phospholipase C (PLC)/protein kinase C pathways, and did not require intact intracellular Ca2+ stores. It was not abolished but enhanced by the GABAA antagonist bicuculline (5 microm), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity. 5. The K+ channel antagonist 4-aminopyridine (4-AP, 50-100 microm) converted the inhibitory effect of DHPG into facilitation. Paired-pulse depression was strongly reduced by DHPG, an effect that was also prevented by 4-AP. 6. Our data indicate that group I agonists regulate transmitter release, presumably via an autoreceptor in the SC. This receptor may be involved in adaptation to repetitive stimulation via a non-PLC mediated pathway.

Using combined whole-cell voltage-clamp recording and Ca2+ imaging we have investigated further the characteristics and pharmacology of group I metabotropic l-glutamate receptor (mGluR)-mediated responses in CA1 pyramidal neurons of the rat hippocampus. The selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), evoked a transient increase in intracellular Ca2+ levels ([Ca2+]i), within neuronal somas and apical dendrites, together with a relatively long lasting inward current (I(DHPG)). Both types of response were enhanced by depolarisation (-30 mV), and this condition was used for their characterisation. The DHPG-induced [Ca2+]i rise was much more sensitive to manipulations of Ca2+ homeostasis, such as using the Ca2+ store depleting agent, cyclopiazonic acid (50-100 microM), the fast Ca2+ buffer, BAPTA (intracellular; 20-40 mM) and Ca(2+)-free/EGTA (1 mM) bath solution, than I(DHPG), suggesting that these responses are, in the main part, mediated by distinct processes. The selective mGluR1 and mGluR5 antagonists, (S)-(+)-alpha-amino-a-methylbenzeneacetic acid (LY367385; 100 microM) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP;10 microM), respectively, markedly inhibited both I(DHPG) and the DHPG-evoked increase in [Ca2+]i. Moreover, these antagonists inhibited the Ca2+ response by more than 50% suggesting a synergistic interaction between mGluR1 and mGluR5. This study demonstrates that in CA1 pyramidal neurons group I mGluR-mediated inward currents and Ca2+ release from intracellular stores are enhanced under depolarising conditions and that mGluR1 and mGluR5 both contribute to these phenomena.

The effect of the single European currency on African economies is uncertain. Many agree that the euro, which will become the sole legal tender in 11 European countries (euroland) after June 30, 2002, will have an economic effect on the 14 African countries that use the CFA franc as their currency, but the direction of that effect is unknown. Currently, euroland and the CFA countries have close trade links. The euro could cause an economic upswing in euroland, leading to a boost in demands for imports, but the euro regime could have a negative impact on certain European sectors that would lead, in turn, to slower export growth in certain sectors of African economies. The CFA-euro link will promote exchange rate stability that could stimulate greater inflows of direct investment into the CFA zone and give CFA borrowers increased access to euroland financial markets. On the other hand, this may mean that CFA borrowers will abandon CFA financial markets. Also, perpetrating a preexisting risk, if the CFA franc becomes devalued because of the strength of the euro, CFA countries may experience a destabilizing loss of capital to euroland. This and other risks were discussed at a November 1998 symposium on the future of the CFA franc zone.

Leptin is an important circulating factor that regulates energy balance via the leptin receptor Ob-Rb1 in the hypothalamus. Ob-Rb activation may inhibit hypothalamic neurons by activating ATP-sensitive K+ channels (KATP channels)2. Here we show that leptin inhibits hippocampal neurons via phosphoinositide 3-kinase (PI3-kinase)–driven activation of large conductance, calcium-activated K+ channels (BK channels), but not KATP channels. This may be an important mechanism for regulating hippocampal excitability.

Endocannabinoids are increasingly being recognized as key lipid-derived regulators of immune function 1. Although the peripheral cannabinoid type 2 receptor (CB2) is thought to orchestrate many of these actions, additional non-CB1/CB2-mediated effects of cannabinoids have been identified in immune cells 1, 2, where several orphan G protein-coupled receptors (GPCRs), including the effusive GPR55, are implicated 3. Despite numerous studies addressing the cannabinoid sensitivity of GPR55, the area remains a pharmacological minefield, with much inconsistent and conflicting data. Emerging provocatively from behind the marijuana smokescreen is a rather surprising, endogenous, lipid ligand at GPR55: namely lysophosphaditylinositol (LPI; 4). In this issue of Cell Research, Balenga and colleagues 5 demonstrates that LPI and the cannabinoid antagonist AM251, have prominent effects on neutrophils that are mediated by GPR55, providing the first compelling evidence for functional GPR55 in blood. In addition, they show that GPR55 forms an intimate but mercurial partnership with the CB2 receptor and that crosstalk between these lipid-sensing GPCRs is likely to be important in fine-tuning the immune response to abrogate excessive tissue injury. Cannabinoids exert varied effects in blood and hematopoietic cells, including modulation of proliferation, apoptosis, cytokine production, reactive oxygen species (ROS) generation, chemotaxis and migration. Indeed, both plant-derived cannabinoids and synthetic CB2 receptor ligands exert well-established anti-inflammatory actions, which are likely be useful therapeutically 1. However, the cannabinoid immunosuppressant dogma does not always hold true, and recent data suggests that the generation of ROS in neutrophils, a key inflammatory event, is in fact promoted by the endocannabinoid 2 arachidonoyl glycerol (2-AG) acting via the CB2 receptor 5. The role of cannabinoids in regulating chemotaxis and directed migration in neutrophils is also controversial, although Balenga and coworkers 5 demonstrate 2-AG-mediated chemotaxis, other studies have not observed this effect 2. There is increasing evidence for non-CB1/CB2 pharmacological targets for cannabinoids and associated lipids in the immune system 1, 2, 6. For example, the endocannabinoid virodhamine and the atypical cannabinoid O-1602 inhibit fMLP-induced migration of human neutrophils via a novel receptor 2 and O-1602 also promotes microglial migration via an interaction with the orphan receptor, GPR18, which was recently heralded as a molecular incarnation of the “abnormal cannabidiol” receptor 6. Moreover, Schicho and coworkers demonstrated that O-1602 inhibits neutrophil recruitment in a model of experimental colitis, via a mechanism that is independent of GPR55 7, thereby implicating an additional target, most likely GPR18. Notwithstanding these observations, as now shown by Balenga and colleagues 5, GPR55 is knocking on the door of this exclusive “novel lipid-sensing cannabinoid GPCR club”, where they demonstrate that both LPI and the aryl pyrazole cannabinoid antagonist AM251 acts as a GPR55 agonists, promoting RhoA-dependent neutrophil chemotaxis, which is reassuringly consistent with previous data using recombinant GPR55 expressed in HEK293 cells 8. The function of endogenous GPR55 is only just emerging, however, there is evidence for expression of GPR55 mRNA in immune tissues 9 and microglia, where it may regulate ERK/MAP kinase signaling following activation 10. Importantly, the study by Balenga and colleagues 5 is now the first to identify a function for GPR55 in leukocytes. GPR55 is unusual in that the majority of its cellular effects are thought to be mediated by G12/13 G-proteins and Rho-family GTPases, including RhoA, Rac1 and Cdc42 9, although a linkage to Gq may occur in certain contexts 3. The latest report is also consistent with this idea, where LPI/GPR55-provoked effects on cytoskeletal remodeling/chemotaxis are mediated via the Gα13/RhoA signaling pathway (5; see Table 1). Interestingly, no clear effect of GPR55 activation alone on Rac1 or Cdc42 was detected in neutrophils, but GTP-Rac2 levels were lowered by LPI treatment, which is important for CB2 receptor crosstalk. Table 1 GPR55 and CB2-mediated signaling in human neutrophils Importantly, Belanga and coworkers identify novel functional interactions between GPR55 (activated with LPI or AM251) and CB2 (activated with 2-AG) receptors in neutrophils. In these cells signaling pathways involving RhoA and Cdc42 are enhanced when both receptors are activated and this is recapitulated using analysis of NFAT activation in HEK293 cells expressing both receptors. In some cases, there is a clear synergism, for example with AM251- and 2-AG-mediated effects on RhoA- mediated chemotaxis (see Table 1). A negative interaction between GPR55 and CB2 is however observed at the level of ROS generation during the “respiratory burst”- a mechanism used by neutrophils to resolve infection. This effect involves crosstalk at the level of the small GTPase Rac2, where LPI markedly represses the response to 2-AG 5. Negative cooperativity between CB2 receptors and a novel SR141716A-sensitive, non-CB1/CB2 pharmacological target inhibiting migration has also been noted previously in neutrophils 2. Many of the features of this latter site are consistent with the “abnormal cannabidiol” receptor although pharmacological crossover with GPR55 (for example when using O-1602 or abnormal cannabidiol) is likely to complicate the picture. Thus in summary, CB2 and GPR55 initially work together with mutually enhanced Rho signaling and directed migration to seek out sites of inflammation. Ultimately they disengage, and in a graceful process of functional repression, GPR55 acts to limit CB2 receptor-mediated collateral damage. In future studies, it will be interesting to extrapolate this GPCR crosstalk into other systems, for example in microglia that express both GPR55 and CB2 receptors. In vivo studies involving GPR55 knockout animals will also help to reveal the role of this receptor in regulating immune function and in models of inflammatory disease. A more detailed profiling of GPR55 expression in different immune cells is required, together with further evaluation of the repertoire of molecular targets for cannabinoids, LPI and related lipids in the immune system.

Nanoclusters are prime objects of study in modern nanotechnology and offer a variety of applications promoted by their properties tunable by size, shape, and composition. DFT calculations are employed to analyze structure, stability, and selected electronic properties of a core-shell C4Al14 species. With insertion of the carbon core, the original low-symmetry aluminum cluster is predicted to undergo a considerable reshaping and acquire a striking D4h tetrakis-hexahedral geometry, with proportions controlled by a near-degenerate spin state or charge. The system also becomes more stable to dissociation. Surprisingly, other properties such as ionisation energy and electron affinity do not change significantly, although still exhibit some interesting features including opposite variations for vertical and adiabatic values. The stability and property evolutions are analyzed in terms of contributions from reshaping of the shell and its further interaction with the core. The system thus has potential applications as a symmetric building unit and a molecular device for nano-electronics/spintronics.

Three-dimensional (3D) object reconstruction is the process of building a 3D model of a real object. This task is performed by taking several scans of an object from different locations (views). Due to the limited field of view of the sensor and the object's self-occlusions, it is a difficult problem to solve. In addition, sensor positioning by robots is not perfect, making the actual view different from the expected one. We propose a next best view (NBV) algorithm that determines each view to reconstruct an arbitrary object. Furthermore, we propose a method to deal with the uncertainty in sensor positioning. The algorithm fulfills all the constraints of a reconstruction process, such as new information, positioning constraints, sensing constraints and registration constraints. Moreover, it improves the scan's quality and reduces the navigation distance. The algorithm is based on a search-based paradigm where a set of candidate views is generated and then each candidate view is evaluated to determine which one is the best. To deal with positioning uncertainty, we propose a second stage which re-evaluates the views according to their neighbours, such that the best view is that which is within a region of the good views. The results of simulation and comparisons with previous approaches are presented.

The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD.

Two novel series of 'Al-kanes' (CnAl2n+2) and 'Al-kenes' (CnAl2n) have been studied theoretically in order to shed light on their structure, stability and properties. Density functional calculations suggest that the structures tend to be dictated by the constituent aluminium atoms, rather than the carbon backbone. This is the net effect of the aluminiums attempting to adopt preferred close-packed structures. Calculated energetics suggest a special stability of clusters with n(C) = 2 and 4 in both series and plausible interpretations are suggested.

Although laypeople and creativity theorists often make the assumption that individual creativity depends primarily on talent, there is considerable evidence that hard work and intrinsic motivation--which can be supported or undermined by the social environment--also play central roles. In this article, the author uses the thoughts and work of the novelist John Irving to illustrate the prominence of nontalent components in the componential model of creativity.

Cannabinoids modulate nociceptive processing in models of acute, inflammatory and neuropathic pain. We have investigated the location and function of cannabinoid receptors on cultured neonatal dorsal root ganglion (DRG) neurones and F-11 cells, a dorsal root ganglionxneuroblastoma hybridoma which displays several of the features of authentic DRG neurones. CB(1) receptor immunolabelling was observed on the cell bodies and as fine puncta on processes of both cultured DRG neurones and F-11 cells. Additionally, fluorescence-activated cell sorting (FACS) analysis provided evidence that both CB(1) and CB(2) receptors are expressed on populations of cells within the cultured DRG and F-11 cells. The cannabinoid receptor agonist (+)-WIN55212 (10 and 100 nM) inhibited the mean voltage-activated Ca(2+) current in DRG neurones by 21% and 30%, respectively. The isomer, (-)-WIN55212 (10 and 100 nM) produced significantly less inhibition of 6% and 10% respectively. The CB(1) selective receptor antagonist SR141716A (100 nM) enhanced the peak high voltage-activated Ca(2+) current by 24% and simultaneous application of SR141716A (100 nM) and (+)-WIN55212 (100 nM) resulted in a significant attenuation of the inhibition obtained with (+)-WIN55212 alone. These data give functional evidence for the hypothesis that the analgesic actions of cannabinoids may be mediated by presynaptic inhibition of transmitter release in sensory neurones.

To determine the effect of delaying the application of the cover glass of a Makler Counting Chamber (Sefi Medical Instruments, Haifa, Israel) on the apparent concentration of sperm or Dynabeads (Dynal Pty Ltd, Carlton, Victoria, Australia).Systematic alteration of the time taken to apply the cover glass.Comprehensive infertility service.Fresh semen from a patient or washed sperm from a donor.For the Makler Counting Chamber, a 5-microL drop of the sperm or bead suspension was placed in the center of the lower platform and the cover glass was applied either immediately (0 seconds) or after a delay of 5, 10, or 30 seconds.The concentration of beads or sperm counted using an Improved Neubauer Hemocytometer or a Makler Counting Chamber.There was a progressive increase in sperm concentration with a longer delay in applying the cover glass when sperm was suspended in either seminal plasma or culture medium. Repeating the experiments with Dynabeads resuspended in phosphate-buffered saline, serum, or seminal plasma showed the same trend, although the suspension of beads in serum seemed to settle the least over the first 10 seconds.Delay in the application of the cover glass is a potential source of error with the Makler Counting Chamber and should be avoided.