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There is wide agreement on the need for systems thinking to address complexity in chronic disease prevention but there is insufficient understanding of how such approaches are operationalised in prevention research. Ison and Straw propose that to address complexity, the right balance must be struck between ‘systemic’ and ‘systematic’ paradigms. We examined the nature and characteristics of this relationship in a series of six qualitative case studies of prevention research. Data comprised 29 semi-structured interviews with 16 participants, and online documents. The analysis combined inductive methods from grounded theory with a theoretically informed framework analysis. Systemic and systematic ways of working varied across each case as a whole, and within the dimensions of each case. Further, the interplay of systemic and systematic approaches was described along a dynamic continuum of variable proportions, with greater emphasis on systemic aspects balanced by less focus on the systematic, and vice versa. By expanding the boundaries for exploring prevention research, we gained empirical understanding of the potential and scope of systemic and systematic paradigms for addressing complexity in prevention research. There is inherent value in being more explicitly conscious and bilingual in both systemic and systematic paradigms so that their respective value and strengths may be utilised. Our findings propose a coherent theoretical frame to better understand existing approaches for addressing complexity in prevention research.

The Martian nakhlite meteorites, which represent multiple events that belong to a single magma source region represent a key opportunity to study the evolution of Martian petrogenesis. Here 16 of the 26 identified nakhlite specimens are studied using coupled electron backscatter diffraction (EBSD) and emplacement end-member calculations. EBSD was used to determine shape preferred orientation (SPO) of contained augite (high Ca-clinopyroxene) phenocrysts by considering their crystallographic preferred orientation (CPO). Parameters derived from EBSD, and energy dispersive X-ray spectroscopy (EDS) data were used in basic emplacement models to assess their dominant mechanism against three end-member scenarios: thermal diffusion, crystal settling, and crystal convection. Results from CPO analyses indicate low intensity weak-moderate CPO. In all samples, a consistent foliation within the axes of augite are observed typically coupled with a weaker lineation CPO in one of the other crystallographic axes. These CPO results agree best with crystal settling being the dominant emplacement mechanism for the nakhlites. Modelled crystal settling results identify two distinguishable groups outside of the model’s resolution indicating the presence of secondary emplacement mechanisms. Comparison of the two identified groups against petrofabric, geochemical, and age parameters indicate random variability between individual meteorites. Therefore, coupled petrofabric and emplacement modelling results identify an overarching characteristic of a dominant crystal settling emplacement mechanism for the nakhlite source volcano despite exhibiting random variation with each discharge through time.

Water uptake is a seminal process in seed germination. Salt and polyethylene glycol (PEG) are known to retard seed germination rates and percentages, which is often attributed to osmotic effects. Here, we quantified water uptake in wheat seeds killed with a hot needle, finding evidence of three distinct water uptake pools. The fast pool was unaffected by salt, and likely represents cell walls and other apoplastic material. Water uptake into the medium and slow pools was slowed by salt addition, with the medium pool thought to be cellular, while the slow pool is presumably related to endosperm hydration. Salt caused a minor decrease in the water uptake rates and maximum seed water content, while PEG strongly suppressed both parameters. Seeds transferred between water and salt solutions followed the water uptake trajectories of the solution into which they were transferred. Seeds transferred from PEG to water achieved final seed water contents similar to water control seeds, while seeds transferred from water to PEG achieved significantly higher final water contents than PEG controls. This work confirms that salt and PEG have distinct effects on water uptake by wheat seeds.

Sampling-based motion planning algorithms are widely used in robotics because they are very effective in high-dimensional spaces. However, the success rate and quality of the solutions are determined by an adequate selection of their parameters such as the distance between states, the local planner, and the sampling distribution. For robots with large configuration spaces or dynamic restrictions, selecting these parameters is a challenging task. This paper proposes a method for improving the performance to a set of the most popular sampling-based algorithms, the Rapidly-exploring Random Trees (RRTs) by adjusting the sampling method. The idea is to replace the uniform probability density function (U-PDF) with a custom distribution (C-PDF) learned from previously successful queries in similar tasks. With a few samples, our method builds a custom distribution that allows the RRT to grow to promising states that will lead to a solution. We tested our method in several autonomous driving tasks such as parking maneuvers, obstacle clearance and under narrow passages scenarios. The results show that the proposed method outperforms the original RRT and several improved versions in terms of success rate, tree density and computation time. In addition, the proposed method requires a relatively small set of examples, unlike current deep learning techniques that require a vast amount of examples., Submitted to BMSE

Grasses have a segmental morphology. Compared to leaf development, data on root development at the phytomer level are scarce. Leaf appearance interval was recorded over time to allow inference about the age of segmental sites that later form roots. Hydroponically grown Lolium perenne cv. Aberdart tillers were studied in both spring and autumn in increasing and decreasing day length conditions, respectively, and dissected to define the development status of roots of known age on successive phytomers basipetally on the tiller axis. Over a 90-day observation period spring and autumn tillers produced 10.4 and 18.1 root bearing phytomers (Pr), respectively. Four stages of root development were identified: (0) main axis elongation (~0–10 days), (1) primary branching (~10–18 days), (2) secondary branching (~18–25 days), and (3) tertiary and quaternary branching without further increase in root dry weight. The individual spring roots achieved significantly greater dry weight (35%) than autumn roots, and a mechanism for seasonal shift in substrate supply to roots is proposed. Our data define a root turnover pattern likely also occurring in field swards and provide insight for modelling the turnover of grass root systems for developing nutrient efficient or stress tolerant ryegrass swards.

Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin–bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82–0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0–0.8%, 1.5–4.8%, and 8.1–19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7–100% and a negative predictive value of 99.3–100%. The cut-off value of 60 resulted in a specificity of 56.6–95.8% and a positive predictive value of 6.6–15.7%. Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. Lay summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin–bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity. © 2020 European Association for the Study of the Liver

The G‐protein‐coupled receptor GPR132, also known as G2A, is activated by 9‐hydroxyoctadecadienoic acid (9‐HODE) and other oxidized fatty acids. Other suggested GPR132 agonists including lysophosphatidylcholine (LPC) have not been readily reproduced. Here, we identify N‐acylamides in particular N‐acylglycines, as lipid activators of GPR132 with comparable activity to 9‐HODE. The order‐of‐potency is N‐palmitoylglycine > 9‐HODE ≈ N‐linoleoylglycine > linoleamide > N‐oleoylglycine ≈ N‐stereoylglycine > N‐arachidonoylglycine > N‐docosehexanoylglycine. Physiological concentrations of N‐acylglycines in tissue are sufficient to activate GPR132. N‐linoleoylglycine and 9‐HODE also activate rat and mouse GPR132, despite limited sequence conservation to human. We describe pharmacological tools for GPR132, identified through drug screening. SKF‐95667 is a novel GPR132 agonist. SB‐583831 and SB‐583355 are peptidomimetic molecules containing core amino acids (glycine and phenylalanine, respectively), and structurally related to previously described ligands. A telmisartan analog, GSK1820795A, antagonizes the actions of N‐acylamides at GPR132. The synthetic cannabinoid CP‐55 940 also activates GPR132. Molecular docking to a homology model suggested a site for lipid binding, predicting the acyl side‐chain to extend into the membrane bilayer between TM4 and TM5 of GPR132. Small‐molecule ligands are envisaged to occupy a “classical” site encapsulated in the 7TM bundle. Structure‐directed mutagenesis indicates a critical role for arginine at position 203 in transmembrane domain 5 to mediate GPR132 activation by N‐acylamides. Our data suggest distinct modes of binding for small‐molecule and lipid agonists to the GPR132 receptor. Antagonists, such as those described here, will be vital to understand the physiological role of this long‐studied target.

The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism.

The abundances of highly siderophile elements (HSE; including Re, Os, Ir, Ru, Pt, and Pd) and (187)Re-(187)Os isotopic systematics were determined for two fragments from ungrouped achondrite NWA 7325. Rhenium-Os systematics are consistent with closed-system behavior since formation or soon after. The abundances of the HSE were therefore largely unaffected by late-stage secondary processes such as shock or terrestrial weathering. As an olivine gabbro cumulate, this meteorite has a bulk composition consistent with derivation from a body that produced a core, mantle and crust. Also consistent with derivation from a body that produced a core, both fragments of NWA 7325 have HSE abundances that are highly depleted compared to bulk chondrites. One fragment has ~0.002 × CI chondrite Ir and relative HSE abundances similar to bulk chondrites. The other fragment has ~0.0002 × CI chondrite Ir, and relative HSE abundances that are fractionated compared to bulk chondrites. The chondritic relative HSE abundances of the fragment characterized by higher HSE abundances most likely reflect the addition of exogenous chondritic material during or after crystallization by surface impacts. The HSE in the other fragment is likely more representative of the parent body crust. One formation model that can broadly account for the HSE abundances in this fragment is multiple episodes of low-pressure metal-silicate equilibration, followed by limited late accretion and mantle homogenization. Given the different HSE compositions of the two adjoining fragments, this meteorite provides an example of the overprint of global processes (differentiation and late accretion) by localized impact contamination.

Despite the importance of roots in determining plant performance, the factors controlling their development and longevity remain poorly understood. Grass morphology is based on repeating units called phytomers, with each capable of producing one leaf, one daughter tiller, and one or more roots. We developed a phytomer-based understanding of root birth, growth and senescence in Lolium perenne, using a modeling approach to explore seasonal effects on root turnover dynamics, and to explore cultivar differences in these processes. Similar to leaves, roots exhibit a clear progression from initiation, growing for approximately seven phyllochrons, with growth rates strongly influenced by environmental conditions. In spring, the phyllochron decreased over the experiment, while it increased in autumn. In spring, C availability exceeding maintenance respiratory requirements allowed root growth at each phytomer position, with a 70/30 split between maintenance and growth. Under C-deficient conditions in autumn, this split was approximately 80/20, with growth limited to younger phytomer positions, while older roots were more susceptible to starvation-induced senescence due to their high C requirements for maintenance respiration.

Plant growth correlates with net carbon gain on a whole plant basis. Over the last several decades, the driving factors shaping plant morphology and performance have become increasingly clear. This review seeks to explore the importance of these factors for grass performance. Briefly, these fall into factors influencing photosynthetic rates directly, competition between plants in a canopy, and nutrient status and availability.

Three-dimensional models from real objects have many applications in robotics. To automatically build a three-dimensional model from an object, it is essential to determine where to place the range sensor in order to completely observe the object. However, the view (position and orientation) of the sensor is not sufficient, given that its corresponding robot state needs to be calculated. Additionally, a collision-free trajectory to reach that state is required. In this article, we directly find the state of the robot whose corresponding sensor view observes the object. This method does not require to calculate the inverse kinematics of the robot. Unlike previous approaches, the proposed method guides the search with a tree structure based on a rapidly exploring random tree overcoming previous sampling techniques. In addition, we propose an information metric that improves the reconstruction performance of previous information metrics.

Purpose in life can provide a sense of intentionality and goal directedness, guide behavior to achieve personal aims and living objectives, foster resilience against life obstacles, and may offer insight into how and why certain people remain healthy over time. A review of the literature was undertaken to identify and consider contemporary research pertaining to purpose and older adults. Thirty two studies were selected for evaluation. Research outcomes were generally consistent in showing that a higher sense of purpose is related to a range of better health and wellbeing outcomes for older adults. Social and environmental factors such as residence and marital status appear to influence the experience of purpose, with community dwelling older adults reporting greater purpose than older adults within a residential or similar type setting, and those married reporting higher purpose than widowed adults. The present research into age and purpose suggests strongly that purpose declines over time. Conversely, it is argued that the potential to experience purpose persists across the life span, by providing opportunities for older adults to continue contributing roles, participate in meaningful activities and sustain their social value and sense of relevance. Further research could target purpose experienced by the oldest old age group, those living within non-community settings, and people with age related cognitive impairment such as dementia, to ensure greater research inclusivity and that benefits associated with purpose can endure throughout one’s life span.

International audience; Paleomagnetic studies of meteorites have shown that the solar nebula was likely magnetized and that many early planetary bodies generated dynamo magnetic fields in their advecting metallic cores. The surface fields on these bodies were recorded by a diversity of chondrites and achondrites, ranging in intensity from several a to several hundred mu T. In fact, an achondrite parent body without evidence for paleomagnetic fields has yet to be confidently identified, hinting that early solar system field generation and the dynamo process in particular may have been common. Here we present paleomagnetic measurements of the ungrouped achondrite NWA 7325 indicating that it last cooled in a near-zero field (

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero® against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero® would prevent only a small absolute number of cases, at a high overall cost.

We prove two estimates for averages of sums of Kloosterman fractions over primes. The first of these improves previous results of Fouvry-Shparlinski and Baker., Comment: 14 pages

We consider almost-primes of the form $f(p)$ where $f$ is an irreducible polynomial over $\mathbb Z$ and $p$ runs over primes. We improve a result of Richert for polynomials of degree at least $3$. In particular we show that, when the degree is large, there are infinitely many primes $p$ for which $f(p)$ has at most $\deg f+O(\log\deg f)$ prime factors., Comment: 17 pages

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.

By establishing an improved level of distribution we study almost primes of the form $f(p,n)$ where $f$ is an irreducible binary form over $\mathbb Z$., 16 pages

Dicopper(II) tetrakis(3,5-diisopropylsalicylate), [Cu(II)2(3,5-DIPS)4], is effective in increasing survival of lethally irradiated mice when it is administered after irradiation. The possibility that this radiorecovery activity might also facilitate recovery from radiation-induced impaired increase in body mass and locomotion was examined. Cu(II)2(3,5-DIPS)4 was used to treat LD50/30 gamma irradiated female C57BL/6 mice after irradiation. A dose of 0, 5, 10, or 20 μmol Cu(II)2 (3,5-DIPS)4 /kilogram of body mass was administered subcutaneously 3 hrs after LD50/30 irradiation and change in body mass and locomotor activity measured daily throughout the 30 day post-irradiation period. Treatment with 5, 10, or 20 μmolCu(II)2(3,5-DIPS)4 /kg of body mass increased survival, which was statistically significant for the 10 μmol /kg of body mass-treated group compared to the vehicle-treated group (P.05) , significantly (P.05) increased recovery of locomotion from days 13 to 15 post-irradiation onward for all treated groups compared to vehicle-treated mice, and increased recovery of body mass gain from day 14 onward for the 20 μmol /kg of body mass-treated group (P.001) and day 21, although not statistically significant, for the 10 μmol /kg of body mass-treated group. There were no statistically significant differences between the increase in survival, recovered increase in body mass, and recovered increase in locomotion for mice treated with 10 μmol or 20 μmolCu(II)2(3,5-DIPS)4 /kg on day 30 post-irradiation. It is concluded that Cu(II)2(3,5-DIPS)4 in addition to increasing survival of irradiated mice increases the rate of recovery of radiation-induced decrease in body mass and locomotion.

International audience; Perennial ryegrass populations previously subjected to two or four cycles of selection for short or long leaf length were studied to determine the response of morphological traits to selection and interaction to determine yield. Measured morphological traits were leaf length, leaf appearance interval, ligule appearance interval, leaf elongation duration, leaf elongation rate, tiller number, tiller dry weight, and herbage dry matter. Additionally, Rubisco concentration during leaf development was measured to determine the association of Rubisco turnover with morphological characteristics and yield. Rubisco was measured and modelled as a three-parameter (D, peak Rubisco concentration; G, time of D; and F, curve width measure), log-normal curve. Leaf length, leaf elongation rate, tiller weight, and plant dry matter diverged after two cycles of selection and further divergence occurred, with these traits being, respectively, 35, 28, 53, and 61% greater in the long-than the short-leaved plants after four cycles of selection. Opposite trends were displayed by Rubisco turnover, with selection for long leaves co-selecting for increased Rubisco turnover time and selection for short leaves resulting in increased leaf Rubisco concentration. There was indication of coupling of leaf appearance with Rubisco turnover. Across populations, multivariate analysis indicated that plant yield was associated with Rubisco concentration rather than Rubisco turnover. The association between higher yield and lower Rubisco concentration could be targeted in the breeding of high-yielding, nitrogen-efficient forage grasses. Plant yield was mainly associated with increased leaf area, indicating that yield could be improved by selecting for longer leaves and faster rates of leaf expansion.

International audience; Angrites formed by some of the earliest igneous activity in the solar system and provide insights into the early stages of planetary melting and differentiation. Moreover, they are pivotal reference points for early solar system chronology. In order to study the processes and timescales of metal segregation in early protoplanets and to assess the distribution of short-lived radionuclides in the early solar system, the Hf-182-W-182 system was applied to a comprehensive suite of angrites. Hf-182-W-182 isochron ages for angrites are in excellent agreement with previously reported Pb-207-Pb-206 and Mn-53-Cr-53 results but are similar to 1 Myr older than ages obtained from Al-26-Mg-26 chronometry. These inconsistencies probably reflect a disturbance of the Al-Mg system in the angrite feldspars, but could alternatively be explained by a heterogeneous distribution of Al-26 in the early solar system. Based on the Hf-W results four texturally and temporally resolved groups of angrites can be identified that were derived from at least two distinct mantle sources. These mantle sources are the result of separate events of core formation, both of which took place within similar to 2 Myr of CAI formation. Thus, core formation in the angrite parent body did not occur as a single event of metal segregation from a global magma ocean but rather took place under varying conditions by several more local events. The disparate Hf-W systematics of the two distinct angrite source regions indicate that convection in the magma ocean was inefficient in homogenizing the composition of the mantle, possibly as a result of a continuous bombardment with small planetesimals during ongoing core formation. Such impacts could have constantly removed primordial and earlier formed crust, facilitating rapid cooling of the magma ocean, which solidified as early as 3.6 +/- 0.7 Myr after CAI formation

Astrocytes possess GPCRs (G-protein-coupled receptors) for neuroactive substances and can respond via these receptors to signals originating from neurons as well as astrocytes. Like many transmembrane proteins, GPCRs exist in a dynamic equilibrium between receptors expressed at the plasma membrane and those present within intracellular trafficking compartments. The characteristics of GPCR trafficking within astrocytes have not been investigated. We therefore monitored the trafficking of recombinant fluorescent protein chimeras of the CB1R (cannabinoid receptor 1) that is thought to be expressed natively in astrocytes. CB1R chimeras displayed a marked punctate intracellular localization when expressed in cultured rat visual cortex astrocytes, an expression pattern reminiscent of native CB1R expression in these cells. Based upon trafficking characteristics, we found the existence of two populations of vesicular CB1R puncta: (i) relatively immobile puncta with movement characteristic of diffusion and (ii) mobile puncta with movement characteristic of active transport along cytoskeletal elements. The predominant direction of active transport is oriented radially to/from the nuclear region, which can be abolished by disruption of the microtubule cytoskeleton. CB1R puncta are localized within intracellular acidic organelles, mainly co-localizing with endocytic compartments. Constitutive trafficking of CB1R to and from the plasma membrane is an energetically costly endeavour whose function is at present unclear in astrocytes. However, given that intracellular CB1Rs can engage cell signalling pathways, it is likely that this process plays an important regulatory role.

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.

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.

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 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.

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.