bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulatory effects of the CCR5 antagonist maraviroc on microglial pro‐inflammatory activation elicited by gp120
Authors: Lisi Lucia , Tramutola Antonella , De Luca Andrea , Navarra Pierluigi , Dello Russo Cinzia 
Published: October 2011

J. Neurochem. (2012) 120, 106–114.AbstractDespite important clinical benefits of the highly active antiretroviral therapy, neurological disorders affect approximately 50% of AIDS patients. In the brain, infected microglia release pro‐inflammatory mediators as well as human immunodeficiency virus type 1 (HIV‐1) proteins, like the envelope protein gp120, that sustain inflammation and mediate neuronal damage. Gp120 allows the virus entry in the host cells via binding to the CD4 receptor together with a specific co‐receptor (CCR5/CXCR4). The antiretroviral drug maraviroc is a CCR5 receptor antagonist, approved for the treatment of HIV‐experienced patients. By interfering with a chemokine receptor, highly expressed in microglia, maraviroc has the potential to modulate their activation during HIV‐1 infection. To test this hypothesis, primary cultures of rat cortical microglia were activated by gp120. Gp120CN54, a protein derived by macrophage (M)‐tropic viruses, showed strong pro‐inflammatory action, thus it was used to test the effects of maraviroc. The latter displayed opposite effects, depending on whether or not interferon‐γ (IFNγ) was also present in the system. IFNγ significantly enhanced gp120 proinflammatory activity, possibly via up‐regulation of CCR5 receptor expression. In this experimental paradigm, maraviroc significantly increased microglial activation, thus suggesting that its chronic use can exacerbate neuronal pathology, especially in HIV‐experienced patients with higher cerebral IFNγ levels.
Identifying priority areas for reducing species vulnerability to climate change
Authors: Crossman Neville D. , Bryan Brett A. , Summers David M 
Published: October 2011

AbstractAim The dimensions of species vulnerability to climate change are complex, and this impedes efforts to provide clear advice for conservation planning. In this study, we used a formal framework to assess species vulnerability to climate change quantifying exposure, sensitivity and adaptive capacity and then used this information to target areas for reducing vulnerability at a regional scale.Location The 6500‐km2Mount Lofty Ranges region in South Australia.Methods We quantified the vulnerability of 171 plant species in a fragmented yet biologically important agro‐ecological landscape, typical of many temperate zones globally. We specified exposure, using three climate change scenarios; sensitivity, as the adverse impact of climate change on species’ spatial distribution; and adaptive capacity, as the ability of species to migrate calculated using dispersal kernels. Priority areas for reducing vulnerability were then identified by incorporating these various components into a single priority index.Results Climate change had a variable impact on species distributions. Those species whose range decreased or shifted geographically were attributed higher sensitivity than those species that increased geographic range or remained unchanged. The ability to adapt to range changes in response to shifting climates varies both spatially and between species. Areas of highest priority for reducing vulnerability were found at higher altitudes and lower latitudes with increasing severity of climate change.Main conclusions Our study demonstrates the use of a single spatially explicit index that identifies areas in the landscape for targeting specific conservation and restoration actions to reduce species vulnerability to climate change. Our index can be transferred to other regions around the world in which climate change poses an increasing threat to native species.
Satellite surface reflectance improves habitat distribution mapping: a case study on heath and shrub formations in the Cantabrian Mountains (NW Spain)
Authors: Morán‐Ordóñez Alejandra , Suárez‐Seoane Susana , Elith Jane , Calvo Leonor , de Luis Estanislao 
Published: October 2011

AbstractAim  We aim to map the distribution of four heath and shrub formations constituting habitats of high conservation priority in Europe, whose occurrence is strongly dependent on human activities. Specifically, we assess whether the use of LANDSAT data in habitat distribution modelling may account for land use management, allowing accurate mapping of real distribution patterns. In particular, we explore whether reflectance values may be a better alternative to other remote sensing data traditionally used in modelling approaches (i.e. spectral vegetation indices and classified land cover maps). Finally, we test whether modelling performance is affected by the ecological traits of the dominant species of the target formations.Location  Cantabrian Mountains (NW Spain).Methods  We generated maps for the four formations (two specialists vs. two generalists) using MaxEnt. First, we ran the models with environmental predictors only (topography, climate, lithology and human disturbances). Then, we compared the advantages of including, in turn, different data derived from LANDSAT imagery: reflectance values (corresponding to different wavelength channels of the multispectral image), a spectral index and a land cover map. We assessed changes in explanatory power and also in the formation’s predicted distribution patterns.Results  Formations dominated by specialist species were accurately mapped on a base of environmental variables only, whereas those dominated by generalists were overpredicted. Average mean temperature, southness and distance to urban areas were the variables contributing most in predictions of environmental models. LANDSAT channels increased the accuracy of all models, but mainly those for formations dominated by generalist species. They showed advantages against other remote sensing data traditionally used in modelling approaches.Main conclusions  Habitat distribution models allowed accurate mapping of heath and shrub formations. The use of reflectance values as predictors improved the accuracy of the models, particularly for formations dominated by generalist species, supplying environmental information that was otherwise unavailable.
Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes
Authors: Bailey RJ , Walker CS , Ferner AH , Loomes KM , Prijic G , Halim A , Whiting L , Phillips ARJ , Hay DL 
Published: October 2011

BACKGROUND AND PURPOSE Amylin (Amy) is an important glucoregulatory peptide and AMY receptors are clinical targets for diabetes and obesity. Human (h) AMY receptor subtypes are complexes of the calcitonin (CT) receptor with receptor activity‐modifying proteins (RAMPs); their rodent counterparts have not been characterized. To allow identification of the most clinically relevant receptor subtype, the elucidation of rat (r) AMY receptor pharmacology is necessary.EXPERIMENTAL APPROACH Receptors were transiently transfected into COS‐7 cells and cAMP responses measured in response to different agonists, with or without antagonists. Competition binding experiments were performed to determine rAmy affinity.KEY RESULTS rCT was the most potent agonist of rCT(a) receptors, whereas rAmy was most potent at rAMY1(a) and rAMY3(a) receptors. rAmy bound to these receptors with high affinity. Rat α‐calcitonin gene‐related peptide (CGRP) was equipotent to rAmy at both AMY receptors. Rat adrenomedullin (AM) and rAM2/intermedin activated all three receptors but were most effective at rAMY3(a). AC187, AC413 and sCT8‐32 were potent antagonists at all three receptors. rαCGRP8‐37 displayed selectivity for rAMY receptors over rCT(a) receptors. rAMY8‐37 was a weak antagonist but was more effective at rAMY1(a) than rAMY3(a).CONCLUSIONS AND IMPLICATIONS AMY receptors were generated by co‐expression of rCT(a) with rRAMP1 or 3, forming rAMY1(a) and rAMY3(a) receptors, respectively. CGRP was more potent at rAMY than at hAMY receptors. No antagonist tested was able to differentiate the rAMY receptor subtypes. The data emphasize the need for and provide a useful resource for developing new CT or AMY receptor ligands as pharmacological tools or potential clinical candidates.LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein‐Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐1
Using microdialysis to analyse the passage of monovalent nanobodies through the blood–brain barrier
Authors: Caljon G , Caveliers V , Lahoutte T , Stijlemans B , Ghassabeh GH , Van Den Abbeele J , Smolders I , De Baetselier P , Michotte Y , Muyldermans S , Magez S , Clinckers R 
Published: October 2011

BACKGROUND AND PURPOSE Nanobodies are promising antigen‐binding moieties for molecular imaging and therapeutic purposes because of their favourable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the CNS remains to be demonstrated.EXPERIMENTAL APPROACH We have assessed the blood–brain barrier permeability of Nb_An33, a nanobody against the Trypanosoma brucei brucei variant‐specific surface glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, single photon emission computed tomography (SPECT) or a combination of both methodologies. This enabled the quantification of unlabelled and 99mTc‐labelled nanobodies using, respectively, a sensitive VSG‐based nanobody‐detection elisa, radioactivity measurement in collected microdialysates and SPECT image analysis.KEY RESULTS The combined read‐out methodologies showed that Nb_An33 was detected in the brain of healthy rats following i.v. injection, inflammation‐induced damage to the blood–brain barrier, as in the late encephalitic stage of trypanosomiasis, significantly increased the efficiency of passage of the nanobody through this barrier. Complementing SPECT analyses with intracerebral microdialysis improved analysis of brain disposition. There is clear value in assessing penetration of the blood–brain barrier by monovalent nanobodies in models of CNS inflammation. Our data also suggest that rapid clearance from blood might hamper efficient targeting of specific nanobodies to the CNS.CONCLUSIONS AND IMPLICATIONS Nanobodies can enter the brain parenchyma from the systemic circulation, especially in pathological conditions where the blood–brain barrier integrity is compromised.
OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies
Authors: Roth Megan , Obaidat Amanda , Hagenbuch Bruno 
Published: October 2011

The human organic anion and cation transporters are classified within two SLC superfamilies. Superfamily SLCO (formerly SLC21A) consists of organic anion transporting polypeptides (OATPs), while the organic anion transporters (OATs) and the organic cation transporters (OCTs) are classified in the SLC22A superfamily. Individual members of each superfamily are expressed in essentially every epithelium throughout the body, where they play a significant role in drug absorption, distribution and elimination. Substrates of OATPs are mainly large hydrophobic organic anions, while OATs transport smaller and more hydrophilic organic anions and OCTs transport organic cations. In addition to endogenous substrates, such as steroids, hormones and neurotransmitters, numerous drugs and other xenobiotics are transported by these proteins, including statins, antivirals, antibiotics and anticancer drugs. Expression of OATPs, OATs and OCTs can be regulated at the protein or transcriptional level and appears to vary within each family by both protein and tissue type. All three superfamilies consist of 12 transmembrane domain proteins that have intracellular termini. Although no crystal structures have yet been determined, combinations of homology modelling and mutation experiments have been used to explore the mechanism of substrate recognition and transport. Several polymorphisms identified in members of these superfamilies have been shown to affect pharmacokinetics of their drug substrates, confirming the importance of these drug transporters for efficient pharmacological therapy. This review, unlike other reviews that focus on a single transporter family, briefly summarizes the current knowledge of all the functionally characterized human organic anion and cation drug uptake transporters of the SLCO and the SLC22A superfamilies.LINKED ARTICLES BJP recently published a themed section on Transporters. To view the papers in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue‐7
Bilobetin ameliorates insulin resistance by PKA‐mediated phosphorylation of PPARα in rats fed a high‐fat diet
Authors: Kou Xin‐Hui , Zhu Mei‐Feng , Chen Dai , Lu Yi , Song Hui‐Zhu , Ye Jian‐Lin , Yue Lin‐Feng 
Published: October 2011

BACKGROUND AND PURPOSE The amelioration of insulin resistance by bilobetin is closely related to its hypolipidaemic effect. The aim of the present study was to determine the insulin‐sensitizing mechanism of bilobetin by elucidating its effect on lipid metabolism.EXPERIMENTAL APPROACH Rats fed a high‐fat diet were treated with bilobetin for either 4 or 14 days before applying a hyperinsulinaemic–euglycaemic clamp. Triglyceride and fatty acids labelled with radioactive isotopes were used to track the transportation and the fate of lipids in tissues. The activity of lipid metabolism‐related enzymes and β‐oxidation rate were measured. Western blot was used to investigate the phosphorylation, translocation and expression of PPARα in several tissues and cultured cells. The location of amino acid residues subjected to phosphorylation in PPARα was also studied.KEY RESULTS Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very‐low‐density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β‐oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity. Threonine‐129–alanine and/or serine‐163–alanine mutations on the PPARα genes and PKA inhibitors prevented the effects of bilobetin on PPARα. However, cells overexpressing PKA appeared to stimulate the phosphorylation, nuclear translocation and activity of PPARα.CONCLUSIONS AND IMPLICATIONS Bilobetin treatment ameliorates hyperlipidaemia, lipotoxicity and insulin resistance in rats by stimulating PPARα‐mediated lipid catabolism. PKA activation is crucial for this process.
Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments
Authors: Keravis Thérèse , Lugnier Claire 
Published: October 2011

Cyclic nucleotide phosphodiesterases (PDEs) that specifically inactivate the intracellular messengers cAMP and cGMP in a compartmentalized manner represent an important enzyme class constituted by 11 gene‐related families of isozymes (PDE1 to PDE11). Downstream receptors, PDEs play a major role in controlling the signalosome at various levels of phosphorylations and protein/protein interactions. Due to the multiplicity of isozymes, their various intracellular regulations and their different cellular and subcellular distributions, PDEs represent interesting targets in intracellular pathways. Therefore, the investigation of PDE isozyme alterations related to various pathologies and the design of specific PDE inhibitors might lead to the development of new specific therapeutic strategies in numerous pathologies.This manuscript (i) overviews the different PDEs including their endogenous regulations and their specific inhibitors; (ii) analyses the intracellular implications of PDEs in regulating signalling cascades in pathogenesis, exemplified by two diseases affecting cell cycle and proliferation; and (iii) discusses perspectives for future therapeutic developments.
So what do we call GPR18 now?
Authors: Alexander SPH 
Published: October 2011

The further characterization of the orphan GPCR GPR18 conducted by McHugh et al. in this issue of the British Journal of Pharmacology has generated a pharmacological profile that raises some interesting questions about the nomenclature of this receptor and may also prompt some questions about the pharmacological definition of the classical cannabinoid receptors, CB1 and CB2.LINKED ARTICLES This article is a commentary on McHugh et al., pp. 2414–2424 of this issue and is part of a themed section on Cannabinoids in Biology and Medicine. To view McHugh et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01497.x. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Role of neurosteroids in the anticonvulsant activity of midazolam
Authors: Dhir Ashish , Rogawski Michael A 
Published: October 2011

BACKGROUND AND PURPOSE Midazolam is a short‐acting benzodiazepine that is widely used as an i.v. sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABAA receptors, some benzodiazepines act as agonists of translocator protein (18 kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABAA receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action.EXPERIMENTAL APPROACH Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the i.v. pentylenetetrazol (PTZ) threshold test.KEY RESULTS Midazolam (500–5000 µg·kg−1, i.p.) caused a dose‐dependent increase in seizure threshold. Pretreatment with the neurosteroid synthesis inhibitors finasteride, a 5α‐reductase inhibitor, and a functional TSPO antagonist PK 11195, reduced the anticonvulsant action of midazolam. The anticonvulsant action of midazolam was enhanced by the neurosteroidogenic drug metyrapone, an 11β‐hydroxylase inhibitor. In contrast, the anticonvulsant action of clonazepam (100 µg·kg−1) was reduced by finasteride but not by PK 11195, indicating a possible contribution of neurosteroids unrelated to TSPO.CONCLUSION AND IMPLICATIONS Enhanced endogenous neurosteroid synthesis, possibly mediated by an interaction with TSPO, contributed to the anticonvulsant action of midazolam. Enhanced neurosteroidogenesis may also be a factor in the actions of other benzodiazepines, even those that only weakly interact with TSPO.
‘But when are they going to produce some artwork?’ Against Pastiche: Issue‐Based Art and Authorship within the Key Stage 3 Curriculum
Authors: Kirlew Stefanie 
Published: October 2011

AbstractIdeas and issues based contemporary art is often seen as something to be avoided in schools, as the controversial subjects that it broaches are often perceived as problematic and inappropriate. However, by censoring education, it can be seen that educators are missing vital opportunities to confront the relevant personal, social, political and cultural issues that shape young peoples' lives in our postmodern, contemporary society. This article reflects on the experiences of an artist/teacher gained through the Recreating Landscapes (Illuminate Project), which aimed to utilise LeWitt's concept of the ideas ‘machine’ to broaden the way that Key Stage 3 art is taught and explore student voice. The construct of the teacher as giver of knowledge was challenged, informed by Barthes' work on the deconstruction of the modernist concept of Authorship. Issues were derived from a pupil voice workshop and the ownership of response to this stimulus belonged to the students. The aim was to challenge mimetic, technical achievement often favoured in ‘traditional’ school art pedagogy, allowing ideas and discussion to be the lynchpin, shifting away from the emphasis commonly placed on outcomes. Through this practice it was hoped that the ‘landscape’ of the learning environment would be recreated: a discursive setting where issues perceived as ‘challenging’ could be broached in a supportive environment, enabled by a reconsidered, culturally relevant pedagogy.
The Artist‐Teacher in the Classroom and Changes in the Teacher–Student Relationship, with Reference to the Issue of Censorship
Authors: Stanhope Clare 
Published: October 2011

AbstractThis article examines a case study of an A‐Level student's work and how the inclusion and integration of my own practice as artist‐teacher into the classroom has changed the teacher‐student relationship, resulting in a more collaborative environment. It investigates how the mutual sharing of practice supports opportunities for pupils to discuss and investigate socially provocative issues and raises the issues of censorship. Through the case study the following questions will be addressed: how a collaborative classroom environment impacts on process and outcomes; the effect of discussing social/ political/ cultural issues within the art and design classroom; and the issues of censorship and ownership within the environment of a comprehensive secondary school context.
‘The falcon cannot hear the falconer …’. The Pedagogical Turn and the Negative Space of Irish Art Education
Authors: Granville Gary 
Published: October 2011

AbstractCurrent education policy discourse in Ireland, as elsewhere, is replete with reference to innovation, creativity and enterprise. Meanwhile, the ‘pedagogical turn’ is a dominant motif in current discourse in art practice, curating and critique, in Ireland and internationally. This article firstly considers some of the implications of the ‘turn’ as a concept in art and education. In that context, it goes on to address changing patterns of curriculum design, development and reform in Ireland. Next, it describes the evolution of Irish education policy over the past decade in the context of global experiences. The particular experience of art education in Ireland is then considered in the light of the curriculum culture and the wider policy discourses already identified. Finally, some implications of the Irish experience are addressed, in terms of art practice at the edges of art education, and art education at the edges of education practice.
From the Saltmarsh and the Deershelter
Authors: Key Paul 
Published: October 2011

AbstractWhen we think about approaches to teaching and learning in art and design education the diverse and complex role of the teacher soon becomes apparent. Teachers often find themselves working through situations which require them to shift between subject‐ and learner‐centred approaches, where they negotiate authority and freedom in their teaching relationships. On closer inspection the tensions found in these negotiations reveal contradictions for teachers, where they try to do one thing but cannot avoid doing another. The article explores these perplexing and contradictory experiences as possible encounters where we can speculate about ourselves as teachers and discover powerful opportunities for learning. It aims to do this through the critical lens of Tubbs's (2005) ‘Philosophy of the teacher’. Tubbs's analysis provides an opportunity to closely examine the tensions in teaching approaches, and proposes the possibility of their contradiction as educational. In addition, the article explores Henri Lefebvre's ‘moments of presence’, suggesting that encounters in our lives, which appear to exist at the intersection of one thing and another, where we find ourselves experiencing a contradiction, offer exciting possibilities for teaching and learning. The article builds its ideas around landscape encounters, from the saltmarsh and the deer‐shelter. It uses these encounters with landscapes to locate experiences of contradiction, and to work out how a teacher could respond.