Possible modulation of dopaminergic neurotransmission function by acetyl-L-carnitine

Acetyl‐L‐Carnitine (ALC) has a putative neuroprotective effect being used in a variety of conditions. Nevertheless, the underlying molecular mechanisms, particularly regarding the induction of changes in neurotransmitter systems, are still not fully understood. We aim to contribute for the elucidation of the mechanisms by which ALC alters neurotransmitter release, using a cell line and an animal model of exposure to methamphetamine (METH). PC12 cells were incubated with several doses of ALC (0.01 to 1.0 mM) alone or in combination with METH 1.0 or 100 µM for 24h or 72h. When combined, ALC preceded METH administration in 30 minutes. Dopamine (DA) content was determined by high performance liquid chromatography. C57BL/6J mice were used for in vivo assays to assess DA striatal binding. Mice were divided into 4 groups, according to different treatments: group 1 (control), group 2 (ALC, 100 mg/kg), group 3 (METH, 10 mg/kg) and group 4 (ALC+METH). Images were acquired in a SPECT/CT scanner (NanoSPECT/CT, Mediso, Hungary) 70 minutes after 123I‐IBZM injection. Regions of interest were drawn in the striata and in the cerebellum to determine the striatal binding ratio. Increased intracellular levels of DA were observed in PC12 cells at 24h and 72h after the administration of ALC. Cells treated with METH 100 µM displayed decreased intracellular levels of DA. ALC prevented the METH‐induced decrease in DA concentration (p<0.0001). On the other hand, a single dose of 10 mg/kg of METH induced a decrease in striatal D2R binding ratios comparing to control group (between 20% and 30%). Interestingly, over time, ALC was able to reverse the decrease on the radiotracer binding induced by METH. The present study indicates a possible effect of ALC over METH‐induced DA release.info:eu-repo/semantics/publishedVersio

Building IKhwezi, a digital platform to capture everyday Indigenous Knowledge for improving educational outcomes in marginalised communities

Aptly captured in the name, the broad mandate of Information and Communications Technologies for Development (ICT4D) is to facilitate the use of Information and Communication Technologies (ICTs) in society to support development. Education, as often stated, is the cornerstone for development, imparting knowledge for conceiving and realising development. In this thesis, we explore how everyday Indigenous Knowledge (IK) can be collected digitally, to enhance the educational outcomes of learners from marginalised backgrounds, by stimulating the production of teaching and learning materials that include the local imagery to have resonance with the learners. As part of the exploration, we reviewed a framework known as Technological Pedagogical Content Knowledge (TPACK), which spells out the different kinds of knowledge needed by teachers to teach effectively with ICTs. In this framework, IK is not present explicitly, but through the concept of context(s). Using Afrocentric and Pan-African scholarship, we argue that this logic is linked to colonialism and a critical decolonising pedagogy necessarily demands explication of IK: to make visible the cultures of the learners in the margins (e.g. Black rural learners). On the strength of this argument, we have proposed that TPACK be augumented to become Indigenous Technological Pedagogical Content Knowledge (I-TPACK). Through this augumentation, I-TPACK becomes an Afrocentric framework for a multicultural education in the digital era. The design of the digital platform for capturing IK relevant for formal education, was done in the Siyakhula Living Lab (SLL). The core idea of a Living Lab (LL) is that users must be understood in the context of their lived everyday reality. Further, they must be involved as co-creators in the design and innovation processes. On a methodological level, the LL environment allowed for the fusing together of multiple methods that can help to create a fitting solution. In this thesis, we followed an iterative user-centred methodology rooted in ethnography and phenomenology. Specifically, through long term conversations and interaction with teachers and ethnographic observations, we conceptualized a platform, IKhwezi, that facilitates the collection of context-sensitive content, collaboratively, and with cost and convenience in mind. We implemented this platform using MediaWiki, based on a number of considerations. From the ICT4D disciplinary point of view, a major consideration was being open to the possibility that other forms of innovation—and, not just ‘technovelty’ (i.e. technological/- technical innovation)—can provide a breakthrough or ingenious solution to the problem at hand. In a sense, we were reinforcing the growing sentiment within the discipline that technology is not the goal, but the means to foregrounding the commonality of the human experience in working towards development. Testing confirmed that there is some value in the platform. This is despite the challenges to onboard users, in pursuit of more content that could bolster the value of everyday IK in improving the educational outcomes of all learners

Fee Arrangements and Fee Shifting: Lessons From the Experience in Ontario

About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen

Multilayered nanoclusters of platinum and gold : insights on electrodeposition pathways, electrocatalysis, surface and bulk compositional properties

Electrochemical, surface and bulk compositional properties of multilayered nanoclusters of Pt and Au, electrochemically deposited on glassy carbon under conditions involving sequential surface–limited redox–replacement reactions (performed at open–circuit) and voltammetric dealloying of templating adlayers of electrodeposited Cu, have been studied in the direction of electrocatalytic applications. Variations in open–circuit potentials during redox–replacement steps indicated thermodynamically–favored formation of Pt(s) and Au(s). Unique bimetallic interfacial active sites, Pt|Au or Au|Pt, were effectively generated as evidenced by their distinct surface electrochemistry and multicomponent X–ray photoelectron spectral features. The bulk and surface–to–near surface distribution of Pt and Au appeared to be influenced by the stoichiometry of the surface redox–replacement reactions and sequential dealloying processes through which the nanoclusters were synthesized. Interactions between metal centers, carbon and oxygen containing surface functional groups on the glassy carbon appeared to have played a significant role in the overall stabilization and catalytic activity of the nanoclusters. Profound effects were also found on interfacial charge–transfer and adsorptive properties involving carbon monoxide and its subsequent electrooxidation to CO2, as well as on the electrocatalytic activity involving formic acid oxidation reaction, where the Pt–rich (Pt|Au) exhibited the highest activity.University of Pretoria and CSIR.http://jes.ecsdl.org/hb2016Chemistr

Fast DNA translocation through a solid-state nanopore

We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR

Al(OH)(3) facilitated synthesis of water-soluble, magnetic, radiolabelled and fluorescent hydroxyapatite nanoparticles

Magnetic and fluorescent hydroxyapatite nanoparticles were synthesised using Al(OH)3-stabilised MnFe2O4 or Fe3O4 nanoparticles as precursors. They were readily and efficiently radiolabelled with 18F. Bisphosphonate polyethylene glycol polymers were utilised to endow the nanoparticles with excellent colloidal stability in water and to incorporate cyclam for high affinity labelling with 64Cu

Decoupling of As and Fe release to Bangladesh groundwater under reducing conditions. Part I: Evidence from sediment profiles

This study reexamines the notion that extensive As mobilization in anoxic groundwater of Bangladesh is intimately linked to the dissolution of Fe oxyhydroxides on the basis of analyses performed on a suite of freshly collected samples of aquifer material. Detailed sediment profiles extending to 40 to 70 m depth below the surface were obtained at six sites where local groundwater As concentrations were known to span a wide range. The sediment properties that were measured include (1) the proportion of Fe(II) in the Fe fraction leached in hot 1.2 N HCl, (2) diffuse spectral reflectance, and (3) magnetic susceptibility. In parallel with local concentrations of dissolved As ranging from <5 to 600 μg/L, Fe(II)/Fe ratios in shallow (gray) Holocene sands tended to gradually increase with depth from values of 0.3 to 0.5 to up to 0.9. In deeper (orange) aquifers of presumed Pleistocene age that were separated from shallow sands by a clay layer and contained <5 μg/L dissolved As, leachable Fe(II)/Fe ratios averaged ∼0.2. There was no consistent relation between sediment Fe(II)/Fe and dissolved Fe concentrations in groundwater in nearby wells. The reflectance measurements indicate a systematic linear relation (R2 of 0.66; n = 151) between the first derivative transform of the reflectance at 520 nm and Fe(II)/Fe. The magnetic susceptibility of the shallow aquifer sands ranged from 200 to 3600 (x 10−9 m3/kg SI) and was linearly related (R2 of 0.75; n = 29) to the concentrations of minerals that could be magnetically separated (0.03 to 0.79% dry weight). No systematic depth trends in magnetic susceptibility were observed within the shallow sands, although the susceptibility of deeper low-As aquifers was low (up to ∼200 × 10−9 m3/kg SI). This set of observations, complemented by incubation results described in a companion paper by van Geen et al. (this volume), suggests that the release of As is linked to the transformation of predominantly Fe (III) oxyhydroxide coatings on sand particles to Fe(II) or mixed Fe(II/III) solid phases with a flatter reflectance spectrum such as siderite, vivianite, or magnetite, without necessarily resulting in the release of Fe to groundwater. The very low As/Fe ratio of magnetically separated minerals compared to the As/Fe of bulk acid leachate (2 vs. 40 10−6, respectively) suggests that such a transformation could be accompanied by a significant redistribution of As to a mobilizable phase on the surface of aquifer particles

Fast microwave-assisted solvothermal synthesis of metal nanoparticles (Pd, Ni, Sn) supported on sulfonated MWCNTs : Pd-based bimetallic catalysts for ethanol oxidation in alkaline medium

The preparation of metal nanoparticles (Pd, Ni, Sn) supported on sulfonated multi-walled carbon nanotubes (SF-MWCNTs) using a very rapid microwave-assisted solvothermal strategy has been described. Electrocatalytic behaviour of the SF-MWCNT-Pd and its ‘mixed’ bimetallic electrocatalysts (i.e., SF-MWCNT-PdSnmix and SF-MWCNT-PdNimix) towards ethanol oxidation in alkaline medium was investigated. The result shows that the mixed Pd-based catalysts (obtained by simple ultrasonic-mixing of the individual MWCNT-metal nanocomposites) gave better electrocatalytic activity than their alloy nanoparticles (obtained by co-reduction of metal salts) or Pd alone. The SF-MWCNT platform gave better electrocatalytic performance compared to the unsulfonated and commercial Vulcan carbons. Detailed electrochemical studies (involving cyclic voltammetry, chronoamperometry, chronopotentiometry, and impedance spectroscopy) prove that the electrocatalytic oxidation of ethanol at the SF-MWCNT-PdNimix platform is more stable, occurs at lower potential, gives lower Tafel slopes, with faster charge-transfer kinetics compared to its SF-MWCNT-PdSnmix counterpart. Also, result revealed that SF-MWCNT-PdNimix is more tolerant to CO poisoning than the SF-MWCNT-PdSnmix. The results provide some important insights into the electrochemical response of microwave-synthesised Pd-based bimetallic catalysts for potential application in direct ethanol alkaline fuel cell technology.The CSIR and NRF.http://www.elsevier.com/locate/electact

Electrocatalytic oxidation of ethylene glycol at palladium-bimetallic nanocatalysts (PdSn and PdNi) supported on sulfonate-functionalised multi-walled carbon nanotubes

Electrocatalytic oxidation of ethylene glycol (EG) in alkaline medium using nano-scaled palladium-based bimetallic catalysts (PdM, where M = Ni and Sn) supported on sulfonated multi-walled carbon nanotubes (SF-MWCNTs) is compared. The bimetallic mixture (i.e., SF-MWCNT–PdSnmix and SF-MWCNT–PdNimix) showed better electrocatalysis towards EG oxidation than the SF-MWCNT–Pd. At the SF-MWCNT– PdSnmix platform, oxidation of EG occurred at lower onset and peak potentials, higher current density, and faster kinetics (lower impedance) than at the SF-MWCNT–PdNimix platform. EG oxidation at the SF-MWCNT–PdNimix is more stable than at the SF-MWCNT–PdSnmix. Indeed, Sn is a more favoured cocatalyst with Pd in EG electro-oxidation.CSIR and NRFhttp://www.elsevier.com/locate/jelechemhb201