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Amidst calls for libraries to regain their socially progressive roots and connections to community, this study analyzes two interwoven cases of nonformal, community education in northeastern Nova Scotia, initiated by libraries that aimed to revive those links. Through a reading circle and a people's school, librarians used historical materials on the Antigonish Movement of that area to help people not only understand their social movement past but also critique what was missing and apply the principles to contemporary problems. The study explored the interplay between identity, locality, and history, as well as the library's role and what could be learned from the activities. This study makes a contribution to adult education in, through, and with libraries in what is currently an underresearched area.

Feminist nonprofit organizations are sites of informal and nonformal learning where citizens learn advocacy, literacy, and the practices of social democracy. With the growing use of information and communication technologies in the nonprofit sector, there are questions as to how well organizations are able to make use of this technology to further their goals of promoting social movement learning and activism. This article reports on a systematic analysis of 100 websites for feminist organizations in Canada. Websites are evaluated for content, currency, and maintenance to determine how well these sites contribute to the work of these organizations. Implications are drawn for learning and teaching in the community-based sphere.

Emerging data indicates the existence of novel molecular targets for cannabinoid ligands and recently it has been suggested that the orphan G-protein coupled receptor, GPR55 can be activated by a range of endogenous, plant and synthetic cannabinoids. However, to date, the most potent ligand identified for GPR55 is the endogenous phospholipid, lysophosphatidylinositol (LPI). GPR55 is thought to link predominantly G-protein alpha(13), where it promotes Rho-dependent signalling. Additional events downstream of GPR55 include activation of ERK-MAP kinase and Ca(2+) release from stores, as well as the induction of a number of transcription factors. Although GPR55 has only a low sequence identity with the CB1 or CB2 cannabinoid receptors, it clearly interacts with certain cannabinoid ligands. However, the nature and scope of these effects are presently unclear and they may be influenced by the assay and cellular background used for their study. This article reviews the current status of GPR55 pharmacology and its putative endogenous ligand, lysophosphatidylinositol LPI.

The hormone leptin can cross the blood–brain barrier and influences numerous brain functions (Harvey, 2007). Indeed, recent studies have demonstrated that leptin regulates activity-dependent synaptic plasticity in the CA1 region of the hippocampus (Shanley et al., 2001; Li et al., 2002; Durakoglugil et al., 2005; Moult et al., 2009). It is well documented that trafficking of AMPA receptors is pivotal for hippocampal synaptic plasticity (Collingridge et al., 2004), but there is limited knowledge of how hormonal systems like leptin influence this process. In this study we have examined how leptin influences AMPA receptor trafficking and in turn how this impacts on excitatory synaptic function. Here we show that leptin preferentially increases the cell surface expression of GluR1 and the synaptic density of GluR2-lacking AMPA receptors in adult hippocampal slices. The leptin-induced increase in surface GluR1 required NMDA receptor activation and was associated with an increase in cytoplasmic PtdIns(3,4,5)P3levels. In addition, leptin enhanced phosphorylation of the lipid phosphatase PTEN which inhibits PTEN function and elevates PtdIns(3,4,5)P3levels. Moreover, inhibition of PTEN mimicked and occluded the effects of leptin on GluR1 trafficking and excitatory synaptic strength. These data indicate that leptin, via a novel pathway involving PTEN inhibition, promotes GluR1 trafficking to hippocampal synapses. This process has important implications for the role of leptin in hippocampal synaptic function in health and disease.

Background and purpose: Increased circulating levels of L-α-lysophosphatidylinositol (LPI) are associated with cancer and LPI is a potent, ligand for the G-protein-coupled receptor GPR55. Here we have assessed the modulation of breast cancer cell migration, orientation and polarization by LPI and GPR55. Experimental approach: Quantitative RT-PCR was used to measure GPR55 expression in breast cancer cell lines. Cell migration and invasion were measured using a Boyden chamber chemotaxis assay and Cultrex® invasion assay, respectively. Cell polarization and orientation in response to the microenvironment were measured using slides containing nanometric grooves. Key results: GPR55 expression was detected in the highly metastatic MDA-MB-231 breast cancer cell line. In these cells, LPI stimulated binding of [35S]GTPγS to cell membranes (pEC50 6.47 ± 0.45) and significantly enhanced cell chemotaxis towards serum. MCF-7 cells expressed low levels of GPR55 and did not migrate or invade towards serum factors. When GPR55 was over-expressed in MCF-7 cells, serum induced a robust migratory and invasive response, which was further enhanced by LPI and prevented by siRNA to GPR55. The physical microenvironment has been identified as a key factor in determining breast tumour cell metastatic fate. LPI endowed MDA-MB-231 cells with the capacity to detect shallow (40 nm deep) grooved slides and induced marked cancer cell polarization on both flat and grooved surfaces. Conclusions and implications: LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x

Background and purpose: Although GPR55 is potently activated by the endogenous lysophospholipid, L-α-lysophosphatidylinositol (LPI), it is also thought to be sensitive to a number of cannabinoid ligands, including the prototypic CB1 receptor antagonists AM251 and SR141716A (Rimonabant®). In this study we have used a range of functional assays to compare the pharmacological activity of selected cannabinoid ligands, AM251, AM281 and SR141716A with LPI in a HEK293 cell line engineered to stably express recombinant, human GPR55.

OBJECTIVE 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 β-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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

We present new compositional data for 30 lunar stones representing about 19 meteorites. Most have iron concentrations intermediate to those of the numerous feldspathic lunar meteorites (3- 7% FeO) and the basaltic lunar meteorites (17-23% FeO). All but one are polymict breccias. Some, as implied by their intermediate composition, are mainly mixtures of brecciated anorthosite and mare basalt, with low concentrations of incompatible elements such as Sm (1-3 µg/g). These breccias likely originate from points on the Moon where mare basalt has mixed with material of the FHT (Feldspathic Highlands Terrane). Others, however, are not anorthosite-basalt mixtures. Three (17- 75 µg/g Sm) consist mainly of nonmare mafic material from the nearside PKT (Procellarum KREEP Terrane) and a few are ternary mixtures of material from the FHT, PKT, and maria. Some contain mafic, nonmare lithologies like anorthositic norites, norites, gabbronorites, and troctolite. These breccias are largely unlike breccias of the Apollo collection in that they are poor in Sm as well as highly feldspathic anorthosite such as that common at the Apollo 16 site. Several have high Th/Sm compared to Apollo breccias. Dhofar 961, which is olivine gabbronoritic and moderately rich in Sm, has lower Eu/Sm than Apollo samples of similar Sm concentration. This difference indicates that the carrier of rare earth elements is not KREEP, as known from the Apollo missions. On the basis of our present knowledge from remote sensing, among lunar meteorites Dhofar 961 is the one most likely to have originated from South Pole-Aitken basin on the lunar far side.

Multiple lines of evidence show that the Rb–Sr, Sm–Nd, and Ar–Ar isotopic systems individually give robust crystallization ages for basaltic (or diabasic) shergottite Northwest Africa (NWA) 1460. In contrast to other shergottites, NWA 1460 exhibits minimal evidence of excess 40Ar, thus allowing an unambiguous determination of its Ar–Ar age. The concordant Rb–Sr, Sm–Nd, and Ar–Ar results for NWA 1460 define its crystallization age to be 346 ± 17 Ma (2σ). In combination with petrographic and trace element data for this specimen and paired meteorite NWA 480, these results strongly refute the suggestion by others that the shergottites are ∼4.1 Ga old. Current crystallization and cosmic-ray exposure (CRE) age data permit identification of a maximum of nine ejection events for Martian meteorites (numbering more than 50 unpaired specimens as of 2008) and plausibly as few as five such events. Although recent high resolution imaging of the Martian surface has identified limited areas of sparsely cratered terrains, the meteorite data suggest that either these areas are representative of larger areas from which the meteorites might come, or that the cratering chronology needs recalibration. Time-averaged 87Rb/86Sr = 0.16 for the mantle source of the parent magma of NWA 1460/480 over the ∼4.56 Ga age of the planet is consistent with previously estimated values for bulk silicate Mars in the range 0.13–0.16, and similar to values of ∼0.18 for the “lherzolitic” shergottites. Initial eNd for NWA 1460/480 at 350 ± 16 Ma ago was +10.6 ± 0.5, which implies a time-averaged 147Sm/144Nd of 0.217 in the Martian mantle prior to mafic melt extraction, similar to values of 0.211–0.216 for the “lherzolitic” shergottites. These time-averaged values do not imply a simple two-stage mantle/melt evolution, but must result from multiple episodes of melt extractions from the source regions. Much higher “late-stage” eNd values for the depleted shergottites imply similar processes carried to a greater degree. Thus, NWA 1460/480, the “lherzolitic” shergottites and perhaps EET 79001 give the best (albeit imperfect) estimate of the Sr- and Nd-isotopic characteristics of bulk silicate Mars.

The endogenous phospholipid L--lyso- phosphatidylinositol (LPI) was recently identified as a novel ligand for the orphan G protein-coupled receptor 55 (GPR55). In this study we define the downstream signaling pathways activated by LPI in a human embry- onic kidney (HEK) 293 cell line engineered to stably express recombinant human GPR55. We find that treatment with LPI induces marked GPR55 internaliza- tion and stimulates a sustained, oscillatory Ca 2 release pathway, which is dependent on G13 and requires RhoA activation. We then establish that this signaling cascade leads to the efficient activation of NFAT (nu- clear factor of activated T cells) family transcription factors and their nuclear translocation. Analysis of cannabinoid ligand activity at GPR55 revealed no clear effect of the endocannabinoids anandamide and 2-arachidonoylglycerol; however, the classical CB1 an- tagonist AM251 evoked GPR55-mediated Ca 2 signal- ing. Thus, LPI is a potent and efficacious ligand at GPR55, which is likely to be a key plasma membrane mediator of LPI-mediated signaling events and changes in gene expression.—Henstridge, C. M., Balenga, N. A. B., Ford, L. A., Ross, R. A., Waldhoer, M., Irving, A. J. The GPR55 ligand L--lysophosphatidylinositol promotes RhoA-dependent Ca 2 signaling and NFAT activation. FASEB J. 23, 000 - 000 (2009)

Using a critical discourse analysis, informed by poststructuralist theory, we explore the research phenomenon of coerced partnership. This lens allows us to pay attention to the social relations of power operating in knowledge generation processes, especially as they affect feminist researchers in adult education. We propose an alternative vision of partnership which politicizes the term partnership, attends to civil society, maps resistances and values the process by all partners.

The shergottites exhibit a range of major and trace element compositions, crystallization ages, and initial Sr, Nd, Hf, and Pb isotopic compositions. To constrain the physical mechanisms by which shergottites obtain their compositional characteristics, we examined the major and trace element record preserved in olivine in the more primitive shergottites. Based on such characteristics as the Mg#, V zoning, calculated DNi,Co, the olivine in Y-980459 are most likely phenocrysts. Many of these same characteristics indicate that the olivines in other shergottites are not in equilibrium with the adjacent melt. However, in most cases they are not xenocrystic, but additions of olivine from the same basaltic system. Elephant Moraine (EET) A79001 may be an exception with the olivine data suggesting that it is xenocrystic. In this case, the olivine crystallized from a reduced and LREEdepleted melt and was incorporated into an oxidized and enriched basalt. Vanadium and CaO in olivine appear to record the appearance of spinel and pyroxene on the liquidus of most of the shergottites. Most of the olivine shergottites represent basalts produced by melting of reduced (IW to IW + 1), depleted mantle sources. Olivine data indicate that many of the primary melts derived from this source had similar Ni, Co, and Mn. Shergottites such as Northwest Africa (NWA) 1110/1068 and perhaps Roberts Massif (RBT) 04261 that appear to be derived from more enriched sources have distinctly different olivine. In the case of NWA 1110/1068, the olivine data suggests that the enriched component was added to system prior to olivine crystallization.

This article provides a feminist poststructural analysis of the authors' academic labor during a State of the Field Literature Review of Gender and Adult Learning for a government-funded educational body. Drawing on Foucault and feminist theorists, the authors pay particular attention to how power seeps down through the system to our bodies in our reading, writing, and analyzing tasks. Using a critically reflexive framework, the authors first examine how government's establishment of knowledge centers and committees, as well as calls for proposals, and work as technologies of power to produce effects such as resistances. Then, attention is turned to their position as feminist researchers who have an ambivalent relationship to some of the field's record on gender and learning. In so doing, the authors interrupt the binary of good researchers/bad government and identify themselves as simultaneously complicit and resistant.

Nakhlite Northwest Africa (NWA) 998 is an augite-rich cumulate igneous rock with mineral compositions and oxygen isotopic composition consistent with an origin on Mars. This 456- gram, partially fusion-crusted meteorite consists of (by volume) ~75% augite (core composition Wo39En39Fs22), ~9% olivine (Fo35), ~7% plagioclase (Ab61An35) as anhedra among augite and olivine, ~3.5% low-calcium pyroxenes (pigeonite and orthopyroxene) replacing or forming overgrowths on olivine and augite, ~1% titanomagnetite, and other phases including potassium feldspar, apatite, pyrrhotite, chalcopyrite, ilmenite, and fine-grained mesostasis material. Minor secondary alteration materials include iddingsite associated with olivine (probably Martian), calcite crack fillings, and iron oxide/hydroxide staining (both probably terrestrial). Shock effects are limited to minor cataclasis and twinning in augite. In comparison to other nakhlites, NWA 998 contains more low-calcium pyroxenes and its plagioclase crystals are blockier. The large size of the intercumulus feldspars and the chemical homogeneity of the olivine imply relatively slow cooling and chemical equilibration in the late- and post-igneous history of this specimen, and mineral thermometers give subsolidus temperatures near 730 °C. Oxidation state was near that of the QFM buffer, from about QFM-2 in earliest crystallization to near QFM in late crystallization, and to about QFM + 1.5 in some magmatic inclusions. The replacement or overgrowth of olivine by pigeonite and orthopyroxene (with or without titanomagnetite), and the marginal replacement of augite by pigeonite, are interpreted to result from late-stage reactions with residual melts (consistent with experimental phase equilibrium relationships). Apatite is concentrated in planar zones separating apatite-free domains, which suggests that residual magma (rich in P and REE) was concentrated in planar (fracture?) zones and possibly migrated through them. Loss of late magma through these zones is consistent with the low bulk REE content of NWA 998 compared with the calculated REE content of its parent magma.

Samarium-neodymium isotopic analyses of unleached and acid-leached mineral fractions from the recently identified olivine-bearing shergottite Northwest Africa 1195 yield a crystallization age of 347 ± 13 Ma and an eNd143 value of +40.1 ± 0.9. Maskelynite fractions do not lie on the Sm–Nd isochron and appear to contain a martian surface component with low 147Sm/144Nd and 143Nd/144Nd ratios that was added during shock. The Rb–Sr system is disturbed and does not yield an isochron. Terrestrial Sr appears to have affected all of the mineral fractions, although a maximum initial 87Sr/86Sr ratio of 0.7016 is estimated by passing a 347 Ma reference line through the maskelynite fraction that is least affected by contamination. The high initial eNd143 value and the low initial 87Sr/86Sr ratio, combined with the geologically young crystallization age, indicate that Northwest Africa 1195 is derived from a source region characterized by a long-term incompatible-element depletion. The age and initial Sr and Nd isotopic compositions of Northwest Africa 1195 are very similar to those of Queen Alexandra Range 94201, indicating these samples were derived from source regions with similar Sr–Nd isotopic systematics. These similarities suggest that these two meteorites share a close petrogenetic relationship and might have been erupted from a common volcano. The meteorites Yamato 980459, Dar al Gani 476, Sayh al Uhaymir 005/008, and Dhofar 019 also have relatively old ages between 474 and 575 Ma and trace element and/or isotopic systematics that are indicative of derivation from incompatible-element-depleted sources. This suggests that the oldest group of meteorites is more closely related to one another than they are to the younger meteorites that are derived from less incompatible-element-depleted sources. Closed-system fractional crystallization of this suite of meteorites is modeled with the MELTS algorithm using the bulk composition of Yamato 980459 as a parent. These models reproduce many of the major element and mineralogical variations observed in the suite. In addition, the rare earth element systematics of these meteorites are reproduced by fractional crystallization using the proportions of phases and extents of crystallization that are calculated by MELTS. Other shergottites that demonstrate enrichments in incompatible-elements and have evolved Sr and Nd isotopic systematics have some geochemical systematics that are similar to those observed in the depleted group. Most notably, although they exhibit a very limited range of incompatible trace element and isotopic compositions, they have highly variable major element compositions. This is also consistent with evolution from a common mantle source region by variable amounts of fractional crystallization. If this scenario is correct, it suggests that the combined effects of source composition and fractional crystallization are likely to account for the major element, trace element, and isotopic diversity of all shergottites.

Leaf Rubisco content was monitored over the life span of the sixth leaf blades of hydroponically grown perennial ryegrass tillers of 18 genotypes, to determine protein turnover patterns and investigate possible links between protein turnover pattern and plant performance. Keywords: Rubisco, perennial ryegrass, remobilisation, dynamic model, mapping population

Two lucerne (Medicago sativa) varieties, an anecdotally waterlogging-intolerant old New Zealand variety, Grasslands Wairau, and a reputedly waterlogging-tolerant new variety, Pioneer 54Q53, were subjected to waterlogging stress and a range of physiological and agronomic measurements performed. Waterlogging stress was characterized by measurement of soil oxygen depletion and soil carbon dioxide accumulation. Both varieties exhibited strong responses to waterlogging stress, including reduction in leaf soluble protein concentration, photosynthetic rate and tap root weight, but also exhibited differences in response, notably a decrease in carboxylation efficiency and in the steady-state quantum yield of electron flow through PSII (ΦPSII) in Wairau, but not in Pioneer. Implications for understanding of waterlogging effects on photosynthesis, and for field management of lucerne on wet soils are discussed.

RIC-3 has been identified as a chaperone molecule involved in promoting the functional expression of nicotinic acetylcholine and 5-HT(3) receptors in mammalian cells. In this study, we examined the effects of RIC-3a (isoform a) and a truncated isoform (isoform d) on RIC-3 localization, mobility, and aggregation and its effect on 5-HT3 receptor composition in mammalian cells. Human RIC-3a possesses an amino-terminal signal sequence that targets it to the endoplasmic reticulum where it is distributed within the reticular network, often forming large diffuse "slicks" and bright "halo" structures. RIC-3a is highly mobile within and between these compartments. Despite the propensity for RIC-3a to aggregate, its expression enhances the level of surface 5-HT3A (homomeric) receptors. In contrast, RIC-3a exerts an inhibitory action on the surface expression of heteromeric 5-HT3A/B receptors. RIC-3d exhibits an altered subcellular distribution, being localized to the endoplasmic reticulum, large diffuse slicks, tubulo-vesicular structures, and the Golgi. Bidirectional trafficking between the endoplasmic reticulum and Golgi suggests that RIC-3d constitutively cycles between these two compartments. In support of the large coiled-coil domain of RIC-3a being responsible for protein aggregation, RIC-3d, lacking this cytoplasmic domain, does not aggregate or induce the formation of bright aggregates. Regardless of these differences, isoform d is still capable of enhancing homomeric, and inhibiting heteromeric, 5-HT3 receptor expression. Thus, both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition.

Recent studies have implicated the hormone leptin in synaptic plasticity associated with neuronal development and learning and memory. Indeed, leptin facilitates hippocampal long-term potentiation and leptin-insensitive rodents display impaired hippocampal synaptic plasticity suggesting a role for endogenous leptin. Structural changes are also thought to underlie activity-dependent synaptic plasticity and this may be regulated by specific growth factors. As leptin is reported to have neurotrophic actions, we have examined the effects of leptin on the morphology and filopodial outgrowth in hippocampal neurons. Here, we demonstrate that leptin rapidly enhances the motility and density of dendritic filopodia and subsequently increases the density of hippocampal synapses. This process is dependent on the synaptic activation of NR2A-containing NMDA receptors and is mediated by the MAPK (ERK) signaling pathway. As dendritic morphogenesis is associated with activity-dependent changes in synaptic strength, the rapid structural remodeling of dendrites by leptin has important implications for its role in regulating hippocampal synaptic plasticity and neuronal development.

N-terminally tagged CB1 receptor fusion proteins, incorporating enhanced green fluorescent protein (GFP) or super-ecliptic pHluorin (SEP), were generated to study CB1 receptor trafficking and cell surface receptor expression in live COS7 and HEK293 cells and hippocampal neurons. An artificial signal sequence (SS) was required for efficient surface expression of CB1 receptor chimeras, which behaved like wild-type CB1 receptors in functional assays. Treatment with cannabinoid ligands led to a rapid down-regulation of SS-GFP-CB1 from the plasma membrane in COS7 and HEK293 cells, associated with trafficking into cytosolic vesicles. Activation of CB1 receptors was also linked with a time-dependent reduction in cell surface SEP-CB1 fluorescence and incorporation of the construct into acidic endosomes, revealed following exposure to NH4Cl. In live hippocampal neurons, SEP-CB1 fluorescence was largely restricted to the axon, consistent with its polarised surface expression. Thus, these new molecular tools are well suited for studying CB1 receptor trafficking and a new generation of GPCR chimeras incorporating SEP at the N-terminus will be especially useful for monitoring dynamic changes in cell surface receptor expression in living cells.

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB 1 Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

Endocannabinoids released during cerebral ischemia have been implicated as neuroprotective agents. We assessed the role of cannabinoid receptors in modulating the response of neurons to oxygen/glucose deprivation (OGD), a model for in vitro ischemia, in rat hippocampal slices using extracellular recording techniques. Under control conditions, 15 min OGD resulted in only 50% recovery of CA1 field excitatory postsynaptic potentials (fEPSPs) 60 min post-insult. This post-OGD depression of function was primarily NMDA receptor-dependent as the NMDA receptor antagonist MK-801 (50 microM) promoted recovery of synaptic transmission to 76% of the baseline. Treatment with the CB1 receptor antagonist AM251 (1 microM), which prevented the depression of excitatory synaptic transmission caused by WIN55,212-2 (1 microM), also markedly enhanced recovery of function (71% of control). The enhanced recovery after OGD in the presence of AM251 was independent of both GABA(A) receptors and NMDA receptors since co-application of AM251 with either bicuculline (10 microM) or MK-801 (50 microM) did not alter recovery, or further improved recovery, respectively. These results suggest endocannabinoids released during OGD may modulate synaptic transmission and post-OGD neuronal outcome via activation of an AM251-sensitive cannabinoid receptor.

To date, many known G protein-coupled receptor 55 (GPR55) ligands are those identified among the cannabinoids. In order to further study the function of GPR55, new potent and selective ligands are needed. In this study, we utilized the screening results from PubChem bioassay AID 1961 which reports the results of Image-based HTS for Selective Agonists of GPR55. Three compounds, CID1792579, CID1252842 and CID1011163, were further evaluated and used as a starting point to create a series of nanomolar potency GPR55 agonists with N-(4-sulfamoylphenyl)thiourea scaffold. The GPR55 activity of the compounds were screened by using a commercial β-arrestin PathHunter assay and the potential compounds were further evaluated by using a recombinant HEK cell line exhibiting GPR55-mediated effects on calcium signalling. The designed compounds were not active when tested against various endocannabinoid targets (CB1R, CB2R, FAAH, MGL, ABHD6 and ABHD12), indicating compounds' selectivity for the GPR55. Finally, structure-activity relationships of these compounds were explored.

L-α-lysophosphatidylinositol (LPI) is the endogenous ligand for GPR55, a Gα13-coupled GPCR. The most abundant endogenous LPI species are stearoyl-LPI (16:0 LPI), palmitoyl-LPI (18:0 LPI) and arachi...

A key area of work for feminists, both inside and outside of organizations, is to build broad-based support for women’s health, often with the help of multiple partners and with a vision of health that transcends clinics and doctors. And, at times, this support has to be built in visible and provocative ways. When Theresa Spence, chief of the Attawapiskat First Nation in Canada, could see what the poor housing and infrastructure crisis was doing to her people, she knew drastic action was called for (Wotherspoon & Hansen, 2013).

Of all the factors that affect women’s lives internationally, religious fundamentalism is one of the most serious in that it has implications for women’s well-being and health and for the population at large. Given the influence that religions, especially fundamentalist factions, have in the fabric of societies worldwide, it is important to examine their place and their effects.

The Raging Grannies defy all stereotypes of older women. Organized globally through local chapters, their members are feminists in “granny-like” costumes who sing protest songs about peace and environmental justice. Seemingly harmless “old women,” they create parodies of traditional songs and sing them in public at rallies and protests. Their chronicler, Carole Roy (2004), sees them as subversive women who utilize both humour and music to communicate and teach citizens about the world they want for themselves and their children and grandchildren.

Adult educator Darlene Clover (2006a, 2007a) brought to international attention an arts in education project that took place at a family services centre on Vancouver Island, Canada. Called Sexual Exploitation Has No Borders, it became a communal quilting project for women who were victims of abuse and social workers who worked with them.

Learning about women’s oppression and the path towards social justice leads to new ways of understanding the issues, as well as new ways of understanding and enacting the learning process itself. Feminist pedagogy draws strength from its engagement with feminism and vice versa.

The Activist Mothers of Xalapa is a group of women in the state of Veracruz, Mexico who provide support for each other in a political struggle with a patriarchal and corrupt government that has allowed their children to be taken from them in custody hearings where false charges are often trumped up against them (Facio, 2013b). This movement draws upon the strong devotion or respect for mothers in Latin cultures and provides a space for mothers to share grief and to take action as a united group.

The mass protests in Cairo’s Tahrir Square during the 2011 Egyptian revolution garnered global media attention. The stories that received less attention were the incidents of harassment and abuse endured by women participants. To draw attention to the violence women faced then, and on an ongoing basis, one young woman, Nihal Saad Zaghloul, began connecting with others through social media.

The Charter of Feminist Principles for African Feminists provides a new model of leadership for African women. Rather than promote the single, independent, charismatic leader, it proposes in this Charter to promote collective leadership that inspires hope, builds on group strengths, and which works counter to patriarchy.

In 1977, 14 women met to form the Mothers of the Plaza de Mayo to find out what had happened to their children who were disappearing in government raids and abductions during Argentina’s Dirty War. The women started marching peacefully in front of the presidential palace to draw attention to the disappeared and to demand the government answer for its crimes and its part in killing their youth.

Collaborative research has the potential to support the work of feminist social and political activism, providing an opportunity for grassroots organizations to come together and to gather the evidence they need to advocate for change. Networks of women’s organizations in Africa, for instance, demonstrate this documentation and mobilizing potential.

In central neurons, the cell-surface distribution of cannabinoid receptor subtype-1 (CB(1)) is highly polarized toward axons and is associated with synaptic terminals, in which it is well-positioned to modulate neurotransmitter release. It has been suggested that high levels of constitutive activity mediate CB(1) receptor axonal targeting, leading to domain-specific endocytosis. We have investigated further the mechanisms that underlie CB(1) receptor axonal polarization in hippocampal neurons and found that constitutive activity is not an essential requirement for this process. We demonstrate that the cell-surface distribution of an N-terminally tagged, fluorescent CB(1) receptor fusion-protein is almost exclusively localized to the axon when expressed in cultured hippocampal neurons. Inhibition of endocytosis by cotransfection with a dominant-negative dynamin-1 (K44A) mutant traps both recombinant and endogenous CB(1) receptors at the somatodendritic cell surface. However, this effect could not be mimicked by inhibiting constitutive activity or receptor activation, either by expressing mutant receptors that lack these properties or by treatment with CB(1) receptor antagonists possessing inverse agonist activity. These data are consistent with a revised model in which domain-specific endocytosis regulates the functional polarization of CB(1) receptors, but this process is distinct from constitutive activity.

Proteinase-activated receptors (PARs1-4) have recently been identified as the molecular entity underlying the cellular effects of serine proteinases. In the present study we have investigated PAR2 signalling, expression and desensitization using cultured and acute slice preparations. Trypsin, SLIGRL and 2f-LIGKV-OH, agonists for PAR2, induced a transient increase in intracellular Ca(2+) levels in both neurons and astrocytes, via activation of the phospholipase C/IP(3) pathway. Furthermore, a single application of trypsin, but not SLIGRL nor 2f-LIGKV-OH, leads to prolonged desensitization of PAR2 responses. PAR2 immunoreactivity was observed in neurons (glutamatergic and GABAergic) and astrocytes within cultures and acute slices, with prominent labelling in neuronal somata and proximal dendrites. Functionally, cultured neurons which exhibited the highest levels of PAR2 labelling, also exhibited the largest Ca(2+) signals upon PAR2 activation. Given the importance of Ca(2+) signalling in hippocampal synaptic plasticity and neurodegeneration, PAR2 may play a key modulatory role in these processes.

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.

Objectives: To complete the audit loop assessing secondary preventative care of patients who had had coronary artery bypass graft (CABG) surgery. Design: Two separate surveys of 1000 patients who had had CABG at the regional centre between 1988 and 1997, selected in 1998 and 2001. A single page questionnaire was sent to the patient’s general practitioner. Interventions: A list was sent to each general practice in Lothian, Scotland, of their patients on the CABG database and the results of the original survey. Lothian Health organised a project to contact and recall patients with cardiac disease in each practice. Sixty five (of 128) practices participated. Main outcome measures: Blood pressure, smoking status, serum cholesterol concentrations, and prescription of lipid lowering drugs and aspirin. Results: 918 questionnaires (92%) in the second survey were returned describing 875 patients: 151 (17%) patients smoked and 752 patients (86%) took aspirin. Mean (SD) systolic blood pressure was lower in the second survey (142.5 (19.2) mm Hg in the first survey v 139.4 (19.1) mm Hg, p < 0.005). In our first survey 34% of patients had cholesterol concentrations less than target (5.2 mmol/l). This increased from 12% of patients operated on in 1988 to 50% of patients operated on in 1997 (Spearman rank correlation 0.77, p < 0.01). In the second survey this proportion had risen to 65% and the correlation with year of operation was abolished. Conclusions: By closing the audit loop, substantial improvements were shown in the management of risk factors in patients who have had coronary artery surgery in Lothian.

Garnet peridotite xenoliths from the Sloan kimberlite (Colorado) are variably depleted in their major magmaphile (Ca, Al) element compositions with whole rock Re-depletion model ages generally consistent with this depletion occurring in the mid-Proterozoic. Unlike many lithospheric peridotites, the Sloan samples are also depleted in incompatible trace elements, as shown by the composition of separated garnet and clinopyroxene. Most of the Sloan peridotites have intermineral Sm–Nd and Lu–Hf isotope systematics consistent with this depletion occurring in the mid-Proterozoic, though the precise age of this event is poorly defined. Thus, when sampled by the Devonian Sloan kimberlite, the compositional characteristics of the lithospheric mantle in this area primarily reflected the initial melt extraction event that presumably is associated with crust formation in the Proterozoic—a relatively simple history that may also explain the cold geotherm measured for the Sloan xenoliths. The Williams and Homestead kimberlites erupted through the Wyoming Craton in the Eocene, near the end of the Laramide Orogeny, the major tectonomagmatic event responsible for the formation of the Rocky Mountains in the late Cretaceous–early Tertiary. Rhenium-depletion model ages for the Homestead peridotites are mostly Archean, consistent with their origin in the Archean lithospheric mantle of the Wyoming Craton. Both the Williams and Homestead peridotites, however, clearly show the consequences of metasomatism by incompatible-element-rich melts. Intermineral isotope systematics in both the Homestead and Williams peridotites are highly disturbed with the Sr and Nd isotopic compositions of the minerals being dominated by the metasomatic component. Some Homestead samples preserve an incompatible element depleted signature in their radiogenic Hf isotopic compositions. Sm–Nd tie lines for garnet and clinopyroxene separates from most Homestead samples provide Mesozoic or younger “ages” suggesting that the metasomatism occurred during the Laramide. Highly variable Rb–Sr and Lu–Hf mineral “ages” for these same samples suggest that the Homestead peridotites did not achieve intermineral equilibrium during this metasomatism. This indicates that the metasomatic overprint likely was introduced shortly before kimberlite eruption through interaction of the peridotites with the host kimberlite, or petrogenetically similar magmas, in the Wyoming Craton lithosphere.

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. 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 μM). This was strongly reduced by the broad-spectrum antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM, ∼95% reduction), by the mGluR1 antagonist LY367385 (100 μM, ∼80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 1–100 μM). The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 μM) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 μM) reduced the effect of CHPG by 50%. 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 μM), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity. The K+ channel antagonist 4-aminopyridine (4-AP, 50–100 μM) 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. 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. British Journal of Pharmacology (2003) 140, 1421–1433. doi:10.1038/sj.bjp.0705570

Different types of fiber-reinforced concrete have been advocated and used as a replacement for welded-wire reinforcement (WWR) in slabs on ground, leading at times to conflicting opinion and/or unrealistic expectation about the benefits of using either WWR or different types of fiber in slabs. In order to verify some of these opinions, tests have been carried out on model slabs (2.5 m×2.5 m×150 mm thick) cast on grade in a test pit and loaded to failure. Results are compared to evaluate the load-carrying capacity for slabs having equivalent amounts of either WWR, fibrillated polypropylene fibers, or steel fibers. Test results show that steel fibers are a suitable alternative to using properly positioned WWR. However, use of polypropylene fibers at a low dosage, which is most common for slab construction (0.9 kg/m³), provides little benefit in terms of increased load-carrying capacity when compared with a plain unreinforced slab. Slab capacity is affected mainly by the postcracking strength of the concrete section, and results from flexure beam tests give a good indication of expected behavior of slabs. The test results also show that a poor subgrade support can be compensated by reinforcing a slab with a moderate amount of either WWR or steel fibers (at a dosage of 30 kg/m³).

The obese gene product, leptin is an important circulating satiety factor that regulates energy balance via its actions in the hypothalamus. However, leptin receptors are also expressed in brain regions not directly associated with energy homeostasis, such as the hippocampus. Here, leptin inhibits hippocampal neurones via activation of large conductance Ca(2+)-activated K(+) (BK) channels, a process that may be important in regulating neuronal excitability. We now show that leptin receptor labelling is expressed on somata, dendrites and axons, and is also concentrated at synapses in hippocampal cultures. In functional studies, leptin potently and reversibly reduces epileptiform-like activity evoked in lean, but not leptin-resistant Zucker fa/fa rats. Furthermore, leptin also depresses enhanced Ca(2+) levels evoked following Mg(2+) removal in hippocampal cultures. The ability of leptin to modulate this activity requires activation of BK, but not K(ATP), channels as the effects of leptin were mimicked by the BK channel activator NS-1619, and inhibited by the BK channel inhibitors, iberiotoxin and charybdotoxin. The signalling mechanisms underlying this process involve stimulation of phosphoinositide 3-kinase (PI 3-kinase), but not mitogen-activated protein kinase (MAPK), as two structurally unrelated inhibitors of PI 3-kinase, LY294002 and wortmannin, blocked the actions of leptin. These data indicate that leptin, via PI 3-kinase-driven activation of BK channels, elicits a novel mechanism for controlling neuronal excitability. As uncontrolled excitability in the hippocampus is one underlying cause of temporal lobe epilepsy, this novel action of leptin could provide an alternative therapeutic target in the management of epilepsy.