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1.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35131937

RESUMO

Land use is central to addressing sustainability issues, including biodiversity conservation, climate change, food security, poverty alleviation, and sustainable energy. In this paper, we synthesize knowledge accumulated in land system science, the integrated study of terrestrial social-ecological systems, into 10 hard truths that have strong, general, empirical support. These facts help to explain the challenges of achieving sustainability in land use and thus also point toward solutions. The 10 facts are as follows: 1) Meanings and values of land are socially constructed and contested; 2) land systems exhibit complex behaviors with abrupt, hard-to-predict changes; 3) irreversible changes and path dependence are common features of land systems; 4) some land uses have a small footprint but very large impacts; 5) drivers and impacts of land-use change are globally interconnected and spill over to distant locations; 6) humanity lives on a used planet where all land provides benefits to societies; 7) land-use change usually entails trade-offs between different benefits-"win-wins" are thus rare; 8) land tenure and land-use claims are often unclear, overlapping, and contested; 9) the benefits and burdens from land are unequally distributed; and 10) land users have multiple, sometimes conflicting, ideas of what social and environmental justice entails. The facts have implications for governance, but do not provide fixed answers. Instead they constitute a set of core principles which can guide scientists, policy makers, and practitioners toward meeting sustainability challenges in land use.


Assuntos
Agricultura , Conservação dos Recursos Naturais/métodos , Ecossistema , Humanos , Energia Renovável , Mudança Social
2.
Faraday Discuss ; 241(0): 341-356, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36254834

RESUMO

Mechanochemical synthesis routes offer a sustainable, simple method for preparing materials. In this work, NiAl2O4 was synthesised by a mechanically activated method using a high-energy planetary mill and a calcination step. This study aims to identify the effect of different milling energies on the phases, chemical environments and surface composition of the material. In addition, it explores the thermal impact on the decomposition and structure of the materials. The materials were characterised by X-ray phosphorescence (XPS), solid-state UV-VIS (SS-UV-VIS), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), high-resolution transmission electron microscopy (HR-TEM) and thermal gravimetry differential scanning calorimetry (TGA-DSC). A co-precipitated material is used as a reference along with the ground reagents which were used as a baseline. From this in-depth analysis of the material, a good understanding of the disordered partially inverse spinel structure is provided. This study has found that with calcination temperatures of 750 °C and 900 °C a mixed NiAl2O4 : NiO phase is produced with a Ni enriched surface. The surface is found to be relatively stable with the increase from 750 °C to 900 °C.

3.
Phys Chem Chem Phys ; 24(4): 2387-2395, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35019919

RESUMO

The effect of Pd loading on the redox characteristics of a ceria support was examined using in situ Pd K-edge XAS, Ce L3-edge XAS and in situ X-ray diffraction techniques. Analysis of the data obtained from these techniques indicates that the onset temperature for the partial reduction of Ce(IV) to Ce(III), by exposure to H2, varies inversely with the loading of Pd. Whilst the onset and completion temperatures of the reduction of Ce(IV) to Ce(III) are different, both samples yield the same maximal fraction of Ce(III) formation independent of Pd loading. Furthermore, the partial reduction of Ce is found to be concurrent with the reduction of PdO and demonstrated that the presence of metallic Pd is necessary for the reduction of the CeO2 support. Upon passivation by room temperature oxidation, a full oxidation of the reduced ceria support was observed. However, only a mild surface oxidation of Pd was identified. The mild passivation of the Pd is found to lead to a highly reactive sample upon a second reduction by H2. The onset of the reduction of Pd and Ce has been demonstrated to be independent of the Pd loading after a mild passivation with both samples exhibiting near room temperature reduction in the presence of H2.

4.
World Dev ; 151: 105757, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34848914

RESUMO

Non-pharmaceutical interventions (NPIs) such as social distancing and travel restrictions have been introduced to prevent the spread of the novel coronavirus (hereinafter Covid). In many countries of the Global South, NPIs are affecting rural livelihoods, but in-depth empirical data on these impacts are limited. We traced the differentiated impacts of Covid NPIs throughout the start of the pandemic May to July 2020. We conducted qualitative weekly phone interviews (n = 441) with 92 panelists from nine contrasting rural communities across Mozambique (3-7 study weeks), exploring how panelists' livelihoods changed and how the NPIs intersected with existing vulnerabilities, and created new exposures. The NPIs significantly re-shaped many livelihoods and placed greatest burdens on those with precarious incomes, women, children and the elderly, exacerbating existing vulnerabilities. Transport and trading restrictions and rising prices for consumables including food meant some respondents were concerned about dying not of Covid, but of hunger because of the disruptions caused by NPIs. No direct health impacts of the pandemic were reported in these communities during our interview period. Most market-orientated income diversification strategies largely failed to provide resilience to the NPI shocks. The exception was one specific case linked to a socially-minded value chain for baobab, where a strong duty of care helped avoid the collapse of incomes seen elsewhere. In contrast, agricultural and charcoal value chains either collapsed or saw producer prices and volumes reduced. The hyper-covariate, unprecedented nature of the shock caused significant restrictions on livelihoods through trading and transport limits and thus a region-wide decline in cash generation opportunities, which was seen as being unlike any prior shock. The scale of human-made interventions and their repercussions thus raises questions about the roles of institutional actors, diversification and socially-minded trading partners in addressing coping and vulnerability both conceptually and in policy-making.

5.
Inorg Chem ; 59(6): 3805-3816, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32091886

RESUMO

The synthesis of a new solid solution of the oxyhydroxide Ga5-xAlxO7(OH) is investigated via solvothermal reaction between gallium acetylacetonate and aluminum isopropoxide in 1,4-butanediol at 240 °C. A limited compositional range of 0 ≤ x ≤ 1.5 is produced, with the hexagonal unit cell parameters refined from powder X-ray diffraction (XRD) showing a linear contraction in unit cell volume with an increase in Al content. Solid-state 27Al and 71Ga nuclear magnetic resonance (NMR) spectroscopies show a strong preference for Ga to occupy the tetrahedral sites and Al to occupy the octahedral sites. Using isopropanol as the solvent, γ-Ga2-xAlxO3 defect spinel solid solutions with x ≤ 1.8 can be prepared at 240 °C in 24 h. These materials are nanocrystalline, as evidenced by their broad diffraction profiles; however, the refined cubic lattice parameter shows a linear relationship with the Ga:Al content, and solid-state NMR spectroscopy again shows a preference for Al to occupy the octahedral sites. Thermal decomposition of Ga5-xAlxO7(OH) occurs via poorly ordered materials that resemble ε-Ga2-xAlxO3 and κ-Ga2-xAlxO3, but γ-Ga2-xAlxO3 transforms above 750 °C to monoclinic ß-Ga2-xAlxO3 for 0 ≤ x ≤ 1.3 and to hexagonal α-Ga2-xAlxO3 for x = 1.8, with intermediate compositions of 1.3 < x < 1.8 giving mixtures of the α- and ß-polymorphs. Solid-state NMR spectroscopy shows only the expected octahedral Al for α-Ga2-xAlxO3, and for ß-Ga2-xAlxO3, the ∼1:2 tetrahedral:octahedral Al ratio is in good agreement with the results of Rietveld analysis of the average structures against powder XRD data. Relative energies calculated by periodic density functional theory confirm that there is an ∼5.2 kJ mol-1 penalty for tetrahedral rather than octahedral Al in Ga5-xAlxO7(OH), whereas this penalty is much smaller (∼2.0 kJ mol-1) for ß-Ga2-xAlxO3, in good qualitative agreement with the experimental NMR spectra.

6.
J Am Chem Soc ; 140(5): 1588-1591, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29350919

RESUMO

Partial substitution of Ce4+ by Nb5+ is possible in CeO2 by coinclusion of Na+ to balance the charge, via hydrothermal synthesis in sodium hydroxide solution. Pair distribution function analysis using reverse Monte Carlo refinement reveals that the small pentavalent substituent resides in irregular coordination positions in an average fluorite lattice, displaced away from the ideal cubic coordination toward four oxygens. This results in under-coordinated oxygen, which explains significantly enhanced oxygen storage capacity of the materials of relevance to redox catalysis used in energy and environmental applications.

7.
Mol Pharm ; 15(5): 1766-1777, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29578347

RESUMO

We describe lead compound MIDD0301 for the oral treatment of asthma based on previously developed positive allosteric α5ß3γ2 selective GABAA receptor (GABAAR) ligands. MIDD0301 relaxed airway smooth muscle at single micromolar concentrations as demonstrated with ex vivo guinea pig tracheal rings. MIDD0301 also attenuated airway hyperresponsiveness (AHR) in an ovalbumin murine model of asthma by oral administration. Reduced numbers of eosinophils and macrophages were observed in mouse bronchoalveolar lavage fluid without changing mucous metaplasia. Importantly, lung cytokine expression of IL-17A, IL-4, and TNF-α were reduced for MIDD0301-treated mice without changing antiinflammatory cytokine IL-10 levels. Automated patch clamp confirmed amplification of GABA induced current mediated by α1-3,5ß3γ2 GABAARs in the presence of MIDD0301. Pharmacodynamically, transmembrane currents of ex vivo CD4+ T cells from asthmatic mice were potentiated by MIDD0301 in the presence of GABA. The number of CD4+ T cells observed in the lung of MIDD0301-treated mice were reduced by an oral treatment of 20 mg/kg b.i.d. for 5 days. A half-life of almost 14 h was demonstrated by pharmacokinetic studies (PK) with no adverse CNS effects when treated mice were subjected to sensorimotor studies using the rotarod. PK studies also confirmed very low brain distribution. In conclusion, MIDD0301 represents a safe and improved oral asthma drug candidate that relaxes airway smooth muscle and attenuates inflammation in the lung leading to a reduction of AHR at a dosage lower than earlier reported GABAAR ligands.


Assuntos
Asma/tratamento farmacológico , Inflamação/tratamento farmacológico , Pulmão/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Animais , Asma/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Líquido da Lavagem Broncoalveolar/química , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Constrição , Citocinas/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Feminino , Cobaias , Inflamação/metabolismo , Ligantes , Pulmão/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Músculo Liso/metabolismo , Ovalbumina/metabolismo , Hipersensibilidade Respiratória/metabolismo
8.
Inorg Chem ; 57(17): 11217-11224, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30106569

RESUMO

The rhodium(III) hydrogarnets Ca3Rh2(OH)12 and Sr3Rh2(OH)12 crystallize as polycrystalline powders under hydrothermal conditions at 200 °C from RhCl3·3H2O and either Ca(OH)2 or Sr(OH)2 in either 12 M NaOH or KOH. Rietveld refinements against synchrotron powder X-ray diffraction (XRD) data allow the first crystal structures of the two materials to be determined. If BaO2 is used as a reagent and the concentration of hydroxide increased to hydroflux conditions (excess NaOH), then single crystals of a new complex rhodium hydroxide, BaNaRh(OH)6, are formed in a phase-pure sample, with sodium included from the flux. Structure solution from single-crystal XRD data reveals isolated octahedral Rh centers that share hydroxides with 10-coordinate Ba and two independent 8-coordinate Na sites. 23Na magic-angle spinning NMR confirms the presence of the two crystallographically distinct Na sites and also verifies the diamagnetic nature of the sample, expected for Rh(III). The thermal behavior of the hydroxides on heating in air was investigated using X-ray thermodiffractometry, showing different decomposition pathways for each material. Ca3Rh2(OH)12 yields CaRh2O4 and CaO above 650 °C, from which phase-pure CaRh2O4 is isolated by washing with dilute nitric acid, a material previously only reported by high-pressure or high-temperature synthesis. Sr3Rh2(OH)12 decomposes to give a less crystalline material with a powder XRD pattern that is matched to the 2H-layered hexagonal perovskite Sr6Rh5O15, which contains mixed-valent Rh3+/4+, confirmed by Rh K-edge XANES spectroscopy. On heating BaNaRh(OH)6, a complex set of decomposition events takes place via transient phases.

9.
Conserv Biol ; 31(2): 353-363, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27558699

RESUMO

A vibrant debate about the future direction of biodiversity conservation centers on the merits of the so-called new conservation. Proponents of the new conservation advocate a series of positions on key conservation ideas, such as the importance of human-dominated landscapes and conservation's engagement with capitalism. These have been fiercely contested in a debate dominated by a few high-profile individuals, and so far there has been no empirical exploration of existing perspectives on these issues among a wider community of conservationists. We used Q methodology to examine empirically perspectives on the new conservation held by attendees at the 2015 International Congress for Conservation Biology (ICCB). Although we identified a consensus on several key issues, 3 distinct positions emerged: in favor of conservation to benefit people but opposed to links with capitalism and corporations, in favor of biocentric approaches but with less emphasis on wilderness protection than prominent opponents of new conservation, and in favor of the published new conservation perspective but with less emphasis on increasing human well-being as a goal of conservation. Our results revealed differences between the debate on the new conservation in the literature and views held within a wider, but still limited, conservation community and demonstrated the existence of at least one viewpoint (in favor of conservation to benefit people but opposed to links with capitalism and corporations) that is almost absent from the published debate. We hope the fuller understanding we present of the variety of views that exist but have not yet been heard, will improve the quality and tone of debates on the subject.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Meio Selvagem , Biologia , Humanos , Organizações
10.
Chemphyschem ; 17(21): 3494-3503, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27569997

RESUMO

The structure of several nano-sized ceria, CeO2 , systems was investigated using neutron and X-ray diffraction and X-ray absorption spectroscopy. Whilst both diffraction and total pair distribution functions (PDFs) revealed that in all of the samples the occupancy of both Ce4+ and O2- are very close to the ideal stoichiometry, the analysis using Reverse Monte Carlo technique revealed significant disorder around oxygen atoms in the nano-sized ceria samples in comparison to the highly crystalline NIST standard. In addition, the analysis revealed that the main differences observed in the pair correlations from various X-ray and neutron diffraction techniques were attributable to the particle size of the CeO2 prepared by the reported three methods. Furthermore, detailed analysis of the Ce L3 - and K-edge EXAFS data support this finding; in particular the decrease in higher shell coordination numbers with respect to the NIST standard, is attributed to differences in particle size.

12.
Angew Chem Int Ed Engl ; 53(17): 4423-7, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-24644102

RESUMO

Low-temperature (200 °C) hydrothermal synthesis of the ruthenium oxides Ca1.5 Ru2 O7 , SrRu2 O6 , and Ba2 Ru3 O9 (OH) is reported. Ca1.5 Ru2 O7 is a defective pyrochlore containing Ru(V/VI) ; SrRu2 O6 is a layered Ru(V) oxide with a PbSb2 O6 structure, whilst Ba2 Ru3 O9 (OH) has a previously unreported structure type with orthorhombic symmetry solved from synchrotron X-ray and neutron powder diffraction. SrRu2 O6 exhibits unusually high-temperature magnetic order, with antiferromagnetism persisting to at least 500 K, and refinement using room temperature neutron powder diffraction data provides the magnetic structure. All three ruthenates are metastable and readily collapse to mixtures of other oxides upon heating in air at temperatures around 300-500 °C, suggesting they would be difficult, if not impossible, to isolate under conventional high-temperature solid-state synthesis conditions.

13.
Sci Data ; 11(1): 229, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388572

RESUMO

Millions of households globally rely on uncultivated ecosystems for their livelihoods. However, much of the understanding about the broader contribution of uncultivated ecosystems to human wellbeing is still based on a series of small-scale studies due to limited availability of large-scale datasets. We pooled together 11 comparable datasets comprising 232 settlements and 10,971 households in ten low-and middle-income countries, representing forest, savanna and coastal ecosystems to analyse how uncultivated nature contributes to multi-dimensional wellbeing and how benefits from nature are distributed between households. The resulting dataset integrates secondary data on rural livelihoods, multidimensional human wellbeing, household demographics, resource tenure and social-ecological context, primarily drawing on nine existing household surveys and their associated contextual information together with selected variables, such as travel time to cities, population density, local area GDP and land use and land cover from existing global datasets. This integrated dataset has been archived with ReShare (UK Data Service) and will be useful for further analyses on nature-wellbeing relationships on its own or in combination with similar datasets.


Assuntos
Ecossistema , Pobreza , Desenvolvimento Sustentável , Humanos , Características da Família , População Rural
14.
J Neurosci ; 32(37): 12928-33, 2012 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-22973017

RESUMO

Kainate receptors can be subject to voltage-dependent block by intracellular polyamines, which causes inward rectification of the current-voltage relationship. Sensitivity to polyamine block is largely determined by the identity of a residue within the pore domain that can be altered through RNA editing. This process causes replacement of the encoded glutamine(Q) with a positively charged arginine(R), eliminating polyamine inhibition and thus inward rectification. In neurons, kainate receptors can associate with the auxiliary subunits Neto1 or Neto2. These transmembrane proteins alter the trafficking, channel kinetics, and pharmacology of the receptors in a subunit-dependent manner. We found that coexpression of Neto subunits with recombinant GluK2(Q) kainate receptors greatly reduced inward rectification without altering calcium permeability. This effect was separate from modulation of channel kinetics, as mutations within the extracellular LDLa domain of the Neto proteins completely eliminated their effects on desensitization but only reduced their effects on rectification. Conversely, deletion of the intracellular C-terminal domain of Neto1 or Neto2 or neutralization of positively charged residues within this domain prevented the reduction in rectification but did not alter effects on channel kinetics. These results demonstrate new roles for Neto1 and Neto2 in regulating kainate receptor function and identify domains within these auxiliary subunits important for mediating their effects.


Assuntos
Cálcio/metabolismo , Ativação do Canal Iônico/fisiologia , Potenciais da Membrana/fisiologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Subunidades Proteicas , Receptores de N-Metil-D-Aspartato , Relação Estrutura-Atividade
15.
J Physiol ; 591(19): 4711-24, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23798491

RESUMO

The ionotropic glutamate receptors are primary mediators of fast excitatory neurotransmission, and their properties are determined both by their subunit composition and their association with auxiliary subunits. The neuropilin and tolloid-like 1 and 2 proteins (Neto1 and Neto2) have been recently identified as auxiliary subunits for kainate-type glutamate receptors. Heteromeric kainate receptors (KARs) can be assembled from varying combinations of low-affinity (GluK1-GluK3) and high-affinity (GluK4-GluK5) subunits. To better understand the functional impact of auxiliary subunits on KARs, we examined the effect of Neto1 on the responses of recombinant homomeric and heteromeric KARs to varying concentrations of glutamate. We found that co-expression of Neto1 with homomeric GluK2 receptors had a small effect on sensitivity of the receptors to glutamate, but decreased the onset of desensitization while speeding recovery from desensitization. In the absence of Neto1, addition of GluK5 subunits to form GluK2/GluK5 heteromeric receptors slowed the onset of desensitization at low glutamate concentrations, compared with GluK2 homomers. Co-expression of Neto1 with GluK2/GluK5 receptors further enhanced these effects, essentially eliminating desensitization at µm glutamate concentrations without altering the EC50 for activation by glutamate. In addition, a prominent rebound current was observed upon removal of the agonist. The rate of recovery from desensitization was increased to the same degree by Neto1 for both homomeric GluK2 and heteromeric GluK2/GluK5 receptors. Expression of Neto1 with GluK1/GluK5, GluK3/GluK5 or GluK2/GluK4 receptors produced qualitatively similar effects on whole-cell currents, suggesting that the impact of Neto1 on the desensitization properties of heteromeric receptors was not subunit dependent. These results provide greater insight into the functional effects of the auxiliary subunit Neto1 on both homomeric and heteromeric KARs. Alteration of the characteristics of desensitization at both sub-maximal and saturating glutamate concentrations could influence the responsiveness of these receptors to repeated stimuli. As a result, assembly of KARs with the Neto auxiliary subunits could change the kinetic properties of the neuronal response to glutamatergic input.


Assuntos
Proteínas de Membrana/metabolismo , Multimerização Proteica , Receptores de Ácido Caínico/metabolismo , Potenciais de Ação , Animais , Ácido Glutâmico/metabolismo , Células HEK293 , Humanos , Ligação Proteica , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ratos , Receptores de N-Metil-D-Aspartato
16.
J Pharmacol Exp Ther ; 347(1): 235-41, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23902941

RESUMO

Many drugs used to treat anxiety are positive modulators of GABAA receptors, which mediate fast inhibitory neurotransmission. The GABAA receptors can be assembled from a combination of at least 16 different subunits. The receptor's subunit composition determines its pharmacologic and functional properties, and subunit expression varies throughout the brain. A primary goal for new treatments targeting GABAA receptors is the production of subunit-selective modulators acting upon a discrete population of receptors. The anxiolytic 4-amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SB-205384) is widely considered to be selective for α3-containing GABAA receptors. However, it has been tested only on α1-, α2-, and α3-containing receptors. We examined the activity of SB-205384 at recombinant receptors containing the six different α subunits and found that receptors containing the α3, α5, and α6 subunits were potentiated by SB-205384, with the α6 subunit conferring the greatest responsiveness. Properties associated with chimeric α1/α6 subunits suggested that multiple structural domains influence sensitivity to SB-205384. Point mutations of residues within the extracellular N-terminal domain identified a leucine residue located in loop E of the agonist binding site as an important determinant of high sensitivity to modulation. In the α6 subunit the identity of this residue is species-dependent, with the leucine found in rat subunits but not in human. Our results indicate that SB-205384 is not an α3-selective modulator, and instead acts at several GABAA receptor isoforms. These findings have implications for the side-effect profile of this anxiolytic as well as for its use in neuronal and animal studies as a marker for contribution from α3-containing receptors.


Assuntos
Aminopiridinas/farmacologia , Receptores de GABA-A/biossíntese , Tiofenos/farmacologia , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Animais , Regulação da Expressão Gênica , Células HEK293 , Humanos , Ratos , Proteínas Recombinantes/biossíntese
17.
Cell Mol Neurobiol ; 33(8): 1099-108, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23975096

RESUMO

Trafficking of ionotropic glutamate receptors to the plasma membrane commonly requires occupation of the agonist binding sites. This quality control check does not typically involve receptor activation, as binding by competitive antagonists or to non-functional channels may also permit surface expression. The tetrameric kainate receptors can be assembled from five different subunits (GluK1-GluK5). While the "low-affinity" GluK1-3 subunits are able to produce functional homomeric receptors, the "high-affinity" GluK4 and GluK5 subunits require co-assembly with GluK1, 2, or 3 for surface expression. These two different types of subunits have distinct functional roles in the receptor. Therefore, we examined the relative importance of occupancy of the agonist site of the GluK2 or GluK5 subunit for surface expression of heteromeric receptors. We created subunits with a mutation within the S2 ligand-binding domain which decreased agonist affinity. Mutations at this site reduced functional surface expression of homomeric GluK2 receptors, but surface expression of these receptors could be increased with either a competitive antagonist or co-assembly with wild-type GluK5. In contrast, mutations in the GluK5 subunit reduced the production of functional heteromeric receptors at the membrane, and could not be rescued with either an antagonist or wild-type GluK2. These findings indicate that ligand binding to only the GluK5 subunit is both necessary and sufficient to allow trafficking of recombinant GluK2/K5 heteromers to the cell membrane, but that occupancy of the GluK2 site alone is not. Our results suggest a distinct role for the GluK5 subunit in regulating surface expression of heteromeric kainate receptors.


Assuntos
Membrana Celular/metabolismo , Multimerização Proteica , Subunidades Proteicas/agonistas , Receptores de Ácido Caínico/agonistas , Receptores de Ácido Caínico/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Membrana Celular/efeitos dos fármacos , Glutamatos/farmacologia , Células HEK293 , Humanos , Ligantes , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Ratos , Receptores de Ácido Caínico/antagonistas & inibidores , Receptores de Ácido Caínico/química , Receptor de GluK2 Cainato
18.
Phys Chem Chem Phys ; 15(40): 17195-207, 2013 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-24013445

RESUMO

This study demonstrates the utility of the novel Field Sweep Fourier Transform (FSFT) method for acquiring wideline (195)Pt NMR data from various sized Pt nanoparticles, Pt-Sn intermetallics/bimetallics used to catalyse oxidative processes in fuel cell applications, and various other related Pt3X alloys (X = Al, Sc, Nb, Ti, Hf and Zr) which can facilitate oxygen reduction catalysis. The (195)Pt and (119)Sn NMR lineshapes measured from the PtSn intermetallic and Pt3Sn bimetallic systems suggest that these are more ordered than other closely related bimetallic alloys; this observation is supported by other characterisation techniques such as XRD. From these reconstructed spectra the mean number of atoms in a Pt nanoparticle can be accurately determined, along with detailed information regarding the number of atoms present effectively in each layer from the surface. This can be compared with theoretical predictions of the number of Pt atoms in these various layers for cubo-octahedral nanoparticles, thereby providing an estimate of the particle size. A comparison of the common NMR techniques used to acquire wideline data from the I = 1/2 (195)Pt nucleus illustrates the advantages of the automated FSFT technique over the Spin Echo Height Spectroscopy (SEHS) (or Spin Echo Integration Spectroscopy (SEIS)) approach that dominates the literature in this area of study. This work also presents the first (195)Pt NMR characterisation of novel small Pt13 nanoclusters which are diamagnetic and thus devoid of metallic character. This unique system provides a direct measure of an isotropic chemical shift for these Pt nanoparticles and affords a better basis for determining the actual Knight shift when compared to referencing against the primary IUPAC shift standard (1.2 M Na2PtCl6(aq)) which has a very different local chemical environment.

19.
Cereb Cortex ; 22(8): 1923-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21980019

RESUMO

We examined how effective connectivity into and out of the left and right temporoparietal areas (TPAs) to/from other key cortical areas affected phonological decoding in 7 dyslexic readers (DRs) and 10 typical readers (TRs) who were young adults. Granger causality was used to compute the effective connectivity of the preparatory network 500 ms prior to presentation of nonwords that required phonological decoding. Neuromagnetic activity was analyzed within the low, medium, and high beta and gamma subbands. A mixed-model analysis determined whether connectivity to or from the left and right TPAs differed across connectivity direction (in vs. out), brain areas (right and left inferior frontal and ventral occipital-temporal and the contralateral TPA), reading group (DR vs. TR), and/or task performance. Within the low beta subband, better performance was associated with increased influence of the left TPA on other brain areas across both reading groups and poorer performance was associated with increased influence of the right TPA on other brain areas for DRs only. DRs were also found to have an increase in high gamma connectivity between the left TPA and other brain areas. This study suggests that hierarchal network structure rather than connectivity per se is important in determining phonological decoding performance.


Assuntos
Dislexia/fisiopatologia , Lateralidade Funcional/fisiologia , Vias Neurais/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Leitura , Análise e Desempenho de Tarefas , Adulto Jovem
20.
Arch Sex Behav ; 42(2): 197-201, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22434397

RESUMO

Female as opposed to male listeners were better able to use a delayed informative cue at the end of a long sentence to report an earlier word which was disrupted by noise. Informative (semantically related) or uninformative (semantically unrelated) word cues were presented 2, 6, or 10 words after a target word whose initial phoneme had been replaced with noise. A total of 84 young adults (45 males) listened to each sentence and then repeated it after its offset. The semantic benefit effect (SBE) was the difference in the accuracy of report of the disrupted target word during informative vs. uninformative sentences. Women had significantly higher SBEs than men even though there were no significant sex differences in terms of number of non-target words reported, the effect of distance between the disrupted target word and the informative cue, or kinds of errors generated. We suggest that the superior ability of women to use delayed semantic information to decode an earlier ambiguous speech signal may be linked to women's tendency to engage the hemispheres more bilaterally than men during word processing. Since the maintenance of semantic context under ambiguous conditions demands more right than left hemispheric resources, this may give women an advantage.


Assuntos
Caracteres Sexuais , Percepção da Fala , Fala , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ruído , Fatores de Tempo
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