Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Adsorption thermodynamics and kinetics study for the self-assembly of 1,8,15,22-tetraaminophthalocyanatocobalt(II) on glassy carbon surface

Spontaneous adsorption of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) on glassy carbon (GC) electrode leads to the formation of a stable self-assembled monolayer (SAM). Since the SAM of 4α-CoIITAPc is redox active, its adsorption on GC electrode was followed by cyclic voltammetry. SAM of 4α-CoIITAPc on GC electrode shows two pairs of well-defined redox peaks corresponding to CoIII/CoII and CoIIIPc−1/CoIIIPc−2. The surface coverage (Γ) value, calculated by integrating the charge under CoII oxidation, was used to study the adsorption thermodynamics and kinetics of 4α-CoIITAPc on GC surface. Cyclic voltammetric studies show that the adsorption of 4α-CoIITAPc on GC electrode has reached the saturation coverage (Γs) within 3 h. The Γs value for the SAM of 4α-CoIITAPc on GC electrode was found to be 2.37 × 10−10 mol cm−2. Gibbs free energy (ΔGads) and adsorption rate constant (kad) for the adsorption of 4α-CoIITAPc on GC surface were found to be −16.76 kJ mol−1 and 7.1 M−1 s−1, respectively. The possible mechanism for the self-assembly of 4α-CoIITAPc on GC surface is through the addition of nucleophilic amines to the olefinic bond on the GC surface in addition to a meager contribution from π stacking. The contribution of π stacking was confirmed from the adsorption of unsubstituted phthalocyanatocobalt(II) (CoPc) on GC electrode. Raman spectra for the SAM of 4α-CoIITAPc on carbon surface shows strong stretching and breathing bands of Pc macrocycle, pyrrole ring and isoindole ring. Raman and CV studies suggest that 4α-CoIITAPc is adopting nearly a flat orientation or little bit tilted orientation.

Electrochemical and spectral studies of self-assembled monolayer of 1,8,15,22-tetraaminophthalocyanatocobalt(II) on indium tin oxide surface

Self-assembled monolayer (SAM) of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) was prepared on indium tin oxide (ITO) electrode by spontaneous adsorption from dimethylformamide (DMF) solution containing 4α-CoIITAPc. The SAM of 4α-CoIITAPc formed on ITO electrode was characterized by cyclic voltammetry, Raman and UV–visible spectroscopic techniques. The cyclic voltammogram (CV) of 4α-CoIITAPc SAM shows two pairs of well-defined redox peaks corresponding to CoIII/CoII and CoIIIPc−1/CoIIIPc−2. The surface coverage (Γ) was calculated by integrating the charge under the anodic wave corresponding to CoII oxidation and it was found to be 2.25 × 10−10 mol cm−2. Raman spectrum obtained for the SAM of 4α-CoIITAPc on ITO surface shows strong stretching and breathing bands of Pc macrocycle, pyrrole ring and isoindole ring. Further, the –NH2 bending mode of vibration was absent for the SAM of 4α-CoIITAPc on ITO surface which indirectly confirmed that all the amino groups of 4α-CoIITAPc are involved in bonding with ITO surface. UV–visible spectrum for the SAM of 4α-CoIITAPc on ITO surface shows an intense B-band, Q-band and n–π∗ transition with slight broadening when compared to that of 4α-CoIITAPc in DMF.

Amino group position dependent orientation of self-assembled monomolecular films of tetraaminophthalocyanatocobalt(II) on Au surfaces

Self-assembled monomolecular films of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) and 2,9,16,23-tetraaminophthalocyanatocobalt(II) (4β-CoIITAPc) on Au surfaces were prepared by spontaneous adsorption from solution. These films were characterized by cyclic voltammetry and Raman spectroscopy. Both the surface coverage (Γ) and intensity of the in-plane stretching bands obtained from Raman studies vary for these monomolecular films, indicating different orientations adopted by them on Au surfaces. The 4α-CoIITAPc-modified electrode exhibits an E1/2 of 0.35 V, while the 4β-CoIITAPc-modified electrode exhibits an E1/2 of 0.19 V, corresponding to the CoII/CoIII redox couple in 0.1 M H2SO4. The Γ estimated from the charge associated with the oxidation of Co(II) gives (2.62 ± 0.10) × 10-11 mol cm-2 for 4α-CoIITAPc and (3.43 ± 0.14) × 10-10 mol cm-2 for 4β-CoIITAPc. In Raman spectral studies, the intensity ratio between in-plane phthalocyanine (Pc) stretching and the Au−N stretching was found to be 6.6 for 4β-CoIITAPc, while it was 1.6 for 4α-CoIITAPc. The obtained lower Γ and intensity ratio values suggest that 4α-CoIITAPc adopts nearly a parallel orientation on the Au surface, while the higher Γ and intensity ratio values suggest that 4β-CoIITAPc adopts a perpendicular orientation. The electrochemical reduction of dioxygen was carried out using these differently oriented Pc's in phosphate buffer solution (pH 7.2). Both the Pc's catalyze the reduction of dioxygen; however, the 4α-CoIITAPc-modified electrode greatly reduces the dioxygen reduction overpotential compared to 4β-CoIITAPc-modified and bare Au electrodes.

Electrocatalytic oxidation of ascorbic acid using a single layer of gold nanoparticles immobilized on 1,6-hexanedithiol modified gold electrode

This paper describes the electrocatalytic oxidation of ascorbic acid (AA) in phosphate buffer solution by the immobilized citrate capped gold nanoparticles (AuNPs) on 1,6-hexanedithiol (HDT) modified Au electrode. X-ray photoelectron spectrum (XPS) of HDT suggests that it forms a monolayer on Au surface through one of the two single bondSH groups and the other single bondSH group is pointing away from the electrode surface. The free single bondSH groups of HDT were used to covalently attach colloidal AuNPs. The covalent attachment of AuNPs on HDT monolayer was confirmed from the observed characteristic carboxylate ion stretching modes of citrate attached with AuNPs in the infra-red reflection absorption spectrum (IRRAS) in addition to a higher reductive desorption charges obtained for AuNPs immobilized on HDT modified Au (Au/HDT/AuNPs) electrode in 0.1 M KOH when compared to HDT modified Au (Au/HDT) electrode. The electron transfer reaction of [Fe(CN)6]4−/3− was markedly hindered at the HDT modified Au (Au/HDT) electrode while it was restored with a peak separation of 74 mV after the immobilization of AuNPs on Au/HDT (Au/HDT/AuNPs) electrode indicating a good electronic communication between the immobilized AuNPs and the underlying bulk Au electrode through a HDT monolayer. The Cottrell slope obtained from the potential-step chronoamperometric measurements for the reduction of ferricyanide at Au/HDT/AuNPs was higher than that of bare Au electrode indicating the increased effective surface area of AuNPs modified electrode. The Au/HDT/AuNPs electrode exhibits excellent electrocatalytic activity towards the oxidation of ascorbic acid (AA) by enhancing the oxidation peak current to more than two times with a 210 mV negative shift in the oxidation potential when compared to a bare Au electrode. The standard heterogeneous electron transfer rate constant (ks) calculated for AA oxidation at Au/HDT/AuNPs electrode was 5.4 × 10−3 cm s−1. The oxidation peak of AA at Au/HDT/AuNPs electrode was highly stable upon repeated potential cycling. Linear calibration plot was obtained for AA over the concentration range of 1–110 μM with a correlation coefficient of 0.9950. The detection limit of AA was found to be 1 μM. The common physiological interferents such as glucose, oxalate ions and urea do not show any interference within the detection limit of AA. The selectivity of the AuNPs modified electrode was illustrated by the determination of AA in the presence of uric acid.

Towards improved precision in the quantification of surface-enhanced Raman scattering (SERS) enhancement factors: A renewed approach

This paper demonstrates a renewed procedure for the quantification of surface-enhanced Raman scattering (SERS) enhancement factors with improved precision. The principle of this method relies on deducting the resonance Raman scattering (RRS) contribution from surface-enhanced resonance Raman scattering (SERRS) to end up with the surface enhancement (SERS) effect alone. We employed 1,8,15,22-tetraaminophthalocyanato-cobalt(II) (4α-CoIITAPc), a resonance Raman- and electrochemically redox-active chromophore, as a probe molecule for RRS and SERRS experiments. The number of 4α-CoIITAPc molecules contributing to RRS and SERRS phenomena on plasmon inactive glassy carbon (GC) and plasmon active GC/Au surfaces, respectively, has been precisely estimated by cyclic voltammetry experiments. Furthermore, the SERS substrate enhancement factor (SSEF) quantified by our approach is compared with the traditionally employed methods. We also demonstrate that the present approach of SSEF quantification can be applied for any kind of different SERS substrates by choosing an appropriate laser line and probe molecule.

Electrochemical pathway for the quantification of SERS enhancement factor

This communication presents a new pathway for the more precise quantification of surface-enhanced Raman scattering (SERS) enhancement factor via deducing resonance Raman scattering (RRS) effect from surface-enhanced resonance Raman scattering (SERRS). To achieve this, a self-assembled monolayer of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) is formed on plasmon inactive glassy carbon (GC) and plasmon active GC/AuNPs surface. The surfaces are subsequently used as common probes for electrochemical and Raman (RRS and SERRS) studies. The most crucial parameters required for the quantification of SERS substrate enhancement factor (SSEF) such as real surface area of GC/AuNPs substarte and the number of 4α-CoIITAPc molecules contributing to RRS (on GC) and SERRS (on GC/AuNPs) are precisely estimated by cyclic voltammetry experiments. The present approach of SSEF quantification can be applied to varieties of surfaces by choosing an appropriate laser line and probe molecule for each surface.

Structure and palaeoenvironmental implications of inter-branch coenosteum-rich skeleton in corymbose Acropora species

Coral reefs provide an increasingly important archive of palaeoclimate data that can be used to constrain climate model simulations. Reconstructing past environmental conditions may also provide insights into the potential of reef systems to survive changes in the Earth’s climate. Reef-based palaeoclimate reconstructions are predominately derived from colonies of massive Porites, with the most abundant genus in the Indo-Pacific—Acropora—receiving little attention owing to their branching growth trajectories, high extension rates and secondary skeletal thickening. However, inter-branch skeleton (consisting of both coenosteum and corallites) near the bases of corymbose Acropora colonies holds significant potential as a climate archive. This region of Acropora skeleton is atypical, having simple growth trajectories with parallel corallites, approximately horizontal density banding, low apparent extension rates and a simple microstructure with limited secondary thickening. Hence, inter-branch skeleton in Acropora bears more similarities to the coralla of massive corals, such as Porites, than to traditional Acropora branches. Cyclic patterns of Sr/Ca ratios in this structure suggest that the observed density banding is annual in nature, thus opening up the potential to use abundant corymbose Acropora for palaeoclimate reconstruction.

The effect of repeated loading and freeze-thaw cycling on immature bovine thoracic motion segment stiffness

There is growing interest in the biomechanics of ‘fusionless’ implant constructs used for deformity correction in the thoracic spine, however, there are questions over the comparability of in vitro biomechanical studies from different research groups due to the various methods used for specimen preparation, testing and data collection. The aim of this study was to identify the effect of two key factors on the stiffness of immature bovine thoracic spine motion segments: (i) repeated cyclic loading and (ii) multiple freeze-thaw cycles, to aid in the planning and interpretation of in vitro studies. Two groups of thoracic spine motion segments from 6-8 week old calves were tested in flexion/extension, right/left lateral bending, and right/left axial rotation under moment control. Group (A) were tested with continuous repeated cyclic loading for 500 cycles with data recorded at cycles 3, 5, 10, 25, 50, 100, 200, 300, 400 and 500. Group (B) were tested after each of five freeze-thaw sequences, with data collected from the 10th load cycle in each sequence. Group A: Flexion/extension stiffness reduced significantly over the 500 load cycles (-22%; P=0.001), but there was no significant change between the 5th and 200th load cycles. Lateral bending stiffness decreased significantly (-18%; P=0.009) over the 500 load cycles, but there was no significant change in axial rotation stiffness (P=0.137). Group B: There was no significant difference between mean stiffness over the five freeze-thaw sequences in flexion/extension (P=0.813) and a near significant reduction in mean stiffness in axial rotation (-6%; P=0.07). However, there was a statistically significant increase in stiffness in lateral bending (+30%; P=0.007). Comparison of in vitro testing results for immature thoracic bovine spine segments between studies can be performed with up to 200 load cycles without significant changes in stiffness. However, when testing protocols require greater than 200 cycles, or when repeated freeze-thaw cycles are involved, it is important to account for the effect of cumulative load and freeze-thaw cycles on spine segment stiffness.

Behaviour of corrugated steel roof cladding under combined wind uplift and racking

During high wind events, crest-fixed profiled steel roof claddings in low-rise buildings can be subjected to combined cyclic wind uplift and in-plane racking (shear) forces. Static and cyclic tests of corrugated steel roof claddings were carried out to investigate the effect of in-plane racking force on the uplift strength, in particular, in relation to the fatigue cracking commonly observed under cyclic wind uplift. The presence of racking force appeared to have insignificant effect on the static and cyclic wind uplift strength. It may therefore be possible to include the diaphragm strength of these claddings in the design of low-rise buildings in a similar manner to valley-fixed claddings. This may lead to a reduction in bracing requirements.

Profiled steel roof claddings under high wind forces

Profiled steel roof claddings in Australia and its neighbouring countries are commonly made of very thin high tensile steel and are crest-fixed intermittently with screw fasteners. The failure of the roof cladding systems was due to a local failure (dimpling of crests I pull-through) at the fasteners under wind uplift Cyclic wind uplift during cyclones causes fatigue cracking to occur at the fastener holes which leads to pull-through failures at lower load levels. At present the design of these claddings is entirely based on testing. In order to improve the understanding of the behaviour and the design and test methods of these claddings under wind uplift loading during storms and cyclones, a detailed investigation consisting of finite element analyses, static and fatigue experiments and cyclonic wind modelling was carried out on two-span roofing assemblies of three common roofing profiles. This paper presents the details of this investigation and its important results.

Towards the design of a scalable and commercially viable technique for plasmid purification using a methacrylate monolithic stationary phase

A monolithic stationary phase was prepared via free radical co-polymerization of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with pore diameter tailored specifically for plasmid binding, retention and elution. The polymer was functionalized. with 2-chloro-N,N-diethylethylamine hydrochloride (DEAE-Cl) for anion-exchange purification of plasmid DNA (pDNA) from clarified lysate obtained from E. coli DH5α-pUC19 culture in a ribonuclease/ protease-free environment. Characterization of the monolithic resin showed a porous material, with 68% of the pores existing in the matrix having diameters above 300 nm. The final product isolated from a single-stage 5 min anion-exchange purification was a pure and homogeneous supercoiled (SC) pDNA with no gDNA, RNA and protein contamination as confirmed by ethidium bromide agarose gel electrophoresis (EtBr-AGE), enzyme restriction analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This non-toxic technique is cGMP compatible and highly scalable for production of pDNA on a commercial level.

Past, present and the evolving future of public health and health promotion: Reflections on dismantling in Queensland Australia

Objective For more than ten years the public health and health promotion workforce in the Australian state of Queensland grew dramatically. This growth was most pronounced in the disciplines of Health Promotion and in Public Health Nutrition, both regionally and corporately. In 2012 political change led to an abrupt dismantling of its public and preventive health services across the state. Individual responsibility was declared. Method This presentation provides a qualitative narrative description of past achievements and activities, the current situation and provides a perspective towards the future. Findings Government reports over several years described the growing burden of chronic disease arising from conditions such as obesity, physical inactivity, and poor nutrition in Queensland. By 2008, obesity had overtaken smoking as the single greatest risk factor to the health of Queenslanders. In 2010, the Chief Health Officer called for an increased focus on prevention to address the continuing need for more beds in hospitals. However, with political change in 2012 resulted in the dismantling and dismissal of preventive health services across the state. The following year, despite outcry, sexual health services were also axed. At present, outbreaks of vaccine preventable diseases such as measles are occurring. The epidemics of chronic disease, obesity and physical inactivity continue to grow. Conclusion The evolution of public health is not necessarily progressive, but cyclic. Challenges include political change, health practice and the interplay of health policy. A lack of an embedded emphasis on systematic review translation is one potential contributor. Perhaps the warning of Lang & Rayner should be heeded: “public health proponents have allowed themselves to be corralled into the narrow language of individualism and choice”.

Green: Exploring the aestheticized use of chroma-key techniques and technologies in two intermedial productions

Peggy Shaw’s RUFF, (USA 2013) and Queensland Theatre Company’s collaboration with Queensland University of Technology, Total Dik!, (Australia 2013) overtly and evocatively draw on an aestheticized use of the cinematic techniques and technologies of Chroma Key to reveal the tensions in their production and add layers to their performances. In doing so they offer invaluable insight where the filmic and theatrical approaches overlap. This paper draws on Eckersall, Grehan and Scheer’s New Media Dramaturgy (2014) to reposition the frame as a contribution to intermedial theatre and performance practices in light of increasing convergence between seemingly disparate discourses. In RUFF, the scenic environment replicates a chroma-key ‘studio’ which facilitates the reconstruction of memory displaced after a stroke. RUFF uses the screen and projections to recall crooners, lounge singers, movie stars, rock and roll bands, and an eclectic line of eccentric family members living inside Shaw. While the show pays tribute to those who have kept her company across decades of theatrical performance, use of non-composited chroma-key technique as a theatrical device and the work’s taciturn revelation of the production process during performance, play a central role in its exploration of the juxtaposition between its reconstructed form and content. In contrast Total Dik! uses real-time green screen compositing during performance as a scenic device. Actors manipulate scale models, refocus cameras and generate scenes within scenes in the construction of the work’s examination of an isolated Dictator. The ‘studio’ is again replicated as a site for (re)construction, only in this case Total Dik! actively seeks to reveal the process of production as the performance plays out. Building on RUFF, and other works such as By the Way, Meet Vera Stark, (2012) and Hotel Modern’s God’s Beard (2012), this work blends a convergence of mobile technologies, models, and green screen capture to explore aspects of transmedia storytelling in a theatrical environment (Jenkins, 2009, 2013). When a green screen is placed on stage, it reads at once as metaphor and challenge to the language of theatre. It becomes, or rather acts, as a ‘sign’ that alludes to the nature of the reconstructed, recomposited, manipulated and controlled. In RUFF and in Total Dik!, it is also a place where as a mode of production and subsequent reveal, it adds weight to performance. These works are informed by Auslander (1999) and Giesenkam (2007) and speak to and echo Lehmann’s Postdramatic Theatre (2006). This paper’s consideration of the integration of studio technique and live performance as a dynamic approach to multi-layered theatrical production develops our understanding of their combinatory use in a live performance environment.

Crystal structures and hydrogen-bonding in the co-crystalline adducts of 3,5-dinitrobenzoic acid with 4-aminosalicylic acid and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid

The structures of the cocrystalline adducts of 3,5-dinitrobenzoic acid (3,5-DNBA) with 4-aminosalicylic acid (PASA), the 1:1 partial hydrate, C7H4N2O6 .C7H7NO3 . 2H2O, (I) and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid (HIPA) and the 1:1:1 d6-dimethylsulfoxide solvate, C7H4N2O6 . C11H9NO3 . C2D6OS, (II) are reported. The crystal substructure of (I) comprises two centrosymmetric hydrogen-bonded R2/2(8) homodimers, one with 3,5-DNBA, the other with PASA, and an R2/2(8) 3,5-DNBA-PASA heterodimer. In the crystal, inter-unit amine N-H...O and water O-H...O hydrogen bonds generate a three-dimensional supramolecular structure. In (II), the asymmetric unit consists of the three constituent molecules which form an essentially planar cyclic hydrogen-bonded heterotrimer unit [graph set R2/3(17)] through carboxyl, hydroxy and amino groups. These units associate across a crystallographic inversion centre through the HIPA carboxylic acid group in an R2/2~(8) hydrogen-bonding association, giving a zero-dimensional structure lying parallel to (100). In both structures, pi--pi interactions are present [minimum ring centroid separations: 3.6471(18)A in (I) and 3.5819(10)A in (II)].