Cleavage of Ru-C(aryl) bond of a four-membered ortho-metalated ruthenium(II) organometallics by mercaptopyrimidine and pyridine-2,6-dicarboxylate ligands: spectroscopic, structural and computational studies

The heterogeneous phase reaction of Ru(η2-RL)(PPh3)2(CO)Cl (1) with 2-mercaptopyrimidine(pymSH) and pyridine-2,6-dicarboxylate(dipic) ligands afforded the complexes of the type Ru(PPh3)(CO)(pymS)2 (2) and Ru(PPh3)2(CO)(dipic) (3) in excellent yield respectively. The chelation of pymS/dipic is attended with the cleavage of Ru-O, Ru-Cl and Ru-C(aryl) bonds and the RL ligand is no longer coordinated with the metal center in the products. The spectral (UV-Vis, IR, 1H NMR) and electrochemical data of the complexes are included. In dichloromethane solution both 2 and 3 display one quasi-reversible RuIII/RuII cyclic voltammetric response with E1/2 in the range 1.15-1.50 V vs Ag/AgCl. Structure determinations of 2 and the solvate 3·CH3CN have revealed distorted octahedral RuCN2S2P coordination sphere for 2 and RuCNO2P2 coordination sphere for 3·CH3CN. For 2 the pairs (P, N), (S, S) and (C, N) define the three trans directions whereas for 3·CH3CN those pairs are (P, P), (C, N) and (O, O). The electronic structures and the absorption spectra of 2 and 3 are also scrutinized by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) analysis.

Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice

This study investigated the effects of riluzole (Ril), creatine (Cr) and a combination of these treatments on the onset and progression of clinical signs and neuropathology in an animal model of familial amyotrophic lateral sclerosis, the G93A transgenic mouse (n=13–17 per group). The onset of clinical signs was delayed (P<0.05) by about 12 days in all treatment groups compared with control; however, no differences occurred between treatments. All animals were killed at 199 days of age. At the end of the experimental period the severity of clinical signs was less (P<0.05) with all treatments compared with control. Again no differences between treatments were observed. The treatments had no effect on the number of neurons in ventral horns of the lumbar region of the spinal cord. Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These data demonstrate that treatment with Ril and Cr were both effective in delaying disease onset and clinical disability. To the age of killing, no additional benefit was conferred by co-administration of Ril and Cr.

Tanshinone IIB, a primary active constituent from Salvia miltiorrhza, exhibits neuro-protective activity in experimentally stroked rats

Tanshinone IIB (TSB) is a major active constituent of the root of Salvia miltiorrhiza (Danshen) used in the treatment of acute stroke. Danshen extracts and TSB have shown marked neuron-protective effects in mouse studies but there is a lack of clinical evidence for the neuron-protective effects of Danshen and its active ingredients. This study investigated the neuron-protective effects of TSB in experimentally stroked rats. TSB at 5 and 25 mg/kg by intraperitoneal injection significantly reduced the focal infarct volume, cerebral histological damage and apoptosis in rats subjected to middle cerebral artery occlusion (MCAO) compared to MCAO rats receiving vehicle. This study demonstrated that TSB was effective in reducing stroke-induced brain damage and may represent a novel drug candidate for further development. Further mechanistic studies are needed for the neuron-protective activity of TSB.

Acylmethyl(aryl)tellurium(IV,II) derivatives : intramolecular secondary bonding and steric rigidity

Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A–1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa–1Ca; Br, 1Ab–1Cb; I, 1Ac–1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe ( 1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te–C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1Ca and 1Cc which are indicative of the presence of intramolecular TeO secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te–C(mesityl) bond axis. Intermolecular C–HO H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state.

Use of high resolution digital multi-spectral imagery to assess the distribution of disease caused by Phytophthora cinnamomi on heathland at Anglesea, Victoria

Disease caused by the soilborne plant pathogen Phytophthora cinnamomi causes long-term floristic and structural changes in native vegetation communities in Australia. Key components of the management of this disease are to know where it occurs and the rate at which it spreads. The distribution of P. cinnamomi has generally been assessed as locality points of infestation and mapping the extent of diseased vegetation in any area is difficult and costly. This study was undertaken in P. cinnamomi-infested heathland communities in southern Victoria, Australia, where the symptoms of P. cinnamomi arise as a mosaic within healthy vegetation. We investigated the potential to improve the efficiency and effectiveness of mapping and monitoring vegetation affected by P. cinnamomi using digital multi-spectral imaging. This technique was developed for the purposes of monitoring vegetation and provides a single, seamless ortho-rectified digital image over the total area of interest. It is used to spatially quantify small differences in the characteristics of vegetation. In this study, the symptoms of disease caused by P. cinnamomi infestation were related to differences in the imagery and were used to map areas of infestation. Comparison of the digital multi-spectral imaging indications with on-ground observations gave moderate accuracy between the datasets (κ = 0.49) for disease and healthy indications. This study demonstrates the ability of the technique to determine disease extent over broad areas in native vegetation and provides a non-invasive, cost effective tool for management.

Positron annihilation lifetime spectroscopy as a probe of free volume in plasticized solid polymer electrolytes

A recent report on the correlation between enhanced polymer mobility and ionic conductivity at room temperature in plasticized polyether-urethane solid polymer electrolytes (Forsyth et al.[1]), has prompted the present investigation. Positron annihilation lifetime spectroscopy (PALS) has been used to study the effect of plasticizer addition on the room temperature free volume characteristics of the crosslinked polyether-urethane. The addition of low molecular weight plasticizers to the polyether-urethane results in a constant or decreasing mean free volume cavity radius, as measured by the orthoPositronium lifetime τ₃, and a decreasing relative concentration of free volume cavities as measured by the ortho-Positronium intensity, I₃. It is postulated that the plasticizers interrupt polymer-polymer interactions by occupying the inter- and intra-chain free volume. The plasticizer structure influences the polymerplasticizer interactions which affect inter- and intra-chain separation and hence the free volume of the system. The decrease in polymer-polymer interaction and the increase in polymer-plasticizer interaction in turn influence the glass transition temperature behaviour.

Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

Background: ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks.
Results: In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals.
Conclusions: In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.

The importance of neighbourhood size in self organising systems

In recent times, the analysis of SOM (self-organising map) performance has concentrated on optimising the gain decay, rather than the size, form and decay of the neighbourhood function. We propose that the size, form and decay of region size plays a much more significant role in the learning, and especially in the development, of topographic feature maps. In this paper, a biologically-derived SOM model is presented. This model is able to select a single winning neuron and to form Gaussian outputs about this winner, without the need for a meta-level decision-making structure to artificially select a winner and fit a Gaussian output to that winner. Using this model, some fundamental characteristics of the relationship between neighbourhood size and SOM output states are demonstrated.

Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy

ATP7A is a P-type ATPase that regulates cellular copper homeostasis by activity at the trans-Golgi network (TGN) and plasma membrane (PM), with the location normally governed by intracellular copper concentration. Defects in ATP7A lead to Menkes disease or its milder variant, occipital horn syndrome or to a newly discovered condition, ATP7A-related distal motor neuropathy (DMN), for which the precise pathophysiology has been obscure. We investigated two ATP7A motor neuropathy mutations (T994I, P1386S) previously associated with abnormal intracellular trafficking. In the patients' fibroblasts, total internal reflection fluorescence microscopy indicated a shift in steady-state equilibrium of ATP7AT994I and ATP7AP1386S, with exaggerated PM localization. Transfection of Hek293T cells and NSC-34 motor neurons with the mutant alleles tagged with the Venus fluorescent protein also revealed excess PM localization. Endocytic retrieval of the mutant alleles from the PM to the TGN was impaired. Immunoprecipitation assays revealed an abnormal interaction between ATP7AT994I and p97/VCP, an ubiquitin-selective chaperone which is mutated in two autosomal dominant forms of motor neuron disease: amyotrophic lateral sclerosis and inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia. Small-interfering RNA (SiRNA) knockdown of p97/VCP corrected ATP7AT994I mislocalization. Flow cytometry documented that non-permeabilized ATP7AP1386S fibroblasts bound a carboxyl-terminal ATP7A antibody, consistent with relocation of the ATP7A di-leucine endocytic retrieval signal to the extracellular surface and partially destabilized insertion of the eighth transmembrane helix. Our findings illuminate the mechanisms underlying ATP7A-related DMN and establish a link between p97/VCP and genetically distinct forms of motor neuron degeneration.

Purity and enrichment of laser-microdissected midbrain dopamine neurons

The ability to microdissect individual cells from the nervous system has enormous potential, as it can allow for the study of gene expression in phenotypically identified cells. However, if the resultant gene expression profiles are to be accurately ascribed, it is necessary to determine the extent of contamination by nontarget cells in the microdissected sample. Here, we show that midbrain dopamine neurons can be laser-microdissected to a high degree of enrichment and purity. The average enrichment for tyrosine hydroxylase (TH) gene expression in the microdissected sample relative to midbrain sections was approximately 200-fold. For the dopamine transporter (DAT) and the vesicular monoamine transporter type 2 (Vmat2), average enrichments were approximately 100- and 60-fold, respectively. Glutamic acid decarboxylase (Gad65) expression, a marker for GABAergic neurons, was several hundredfold lower than dopamine neuron-specific genes. Glial cell and glutamatergic neuron gene expression were not detected in microdissected samples. Additionally, SN and VTA dopamine neurons had significantly different expression levels of dopamine neuron-specific genes, which likely reflects functional differences between the two cell groups. This study demonstrates that it is possible to laser-microdissect dopamine neurons to a high degree of cell purity. Therefore gene expression profiles can be precisely attributed to the targeted microdissected cells.

Review of trust and machine ethics research: towards a bio-inspired computational model of ethical trust (CMET)

Recent advances in the fields of robotics, cyborg development, moral psychology, trust, multi agent-based systems and socionics have raised the need for a better understanding of ethics, moral reasoning, judgment and decision-making within the system of man and machines. Here we seek to understand key research questions concerning the interplay of ethical trust at the individual level and the social moral norms at the collective end. We review salient works in the fields of trust and machine ethics research, underscore the importance and the need for a deeper understanding of ethical trust at the individual level and the development of collective social moral norms. Drawing upon the recent findings from neural sciences on mirror-neuron system (MNS) and social cognition, we present a bio-inspired Computational Model of Ethical Trust (CMET) to allow investigations of the interplay of ethical trust and social moral norms.

An examination of the influence of visuomotor associations on interpersonal motor resonance

The adaptation account of mirror neurons in humans proposes that mirror systems have been selected for in evolution to facilitate social cognition. By contrast, a recent "association" account of mirror neurons in humans argues that mirror systems are not the result of a specific adaptation, but of sensorimotor learning arising from concurrent visual and motor activity. Here, we used transcranial magnetic stimulation (TMS) and electromyography (EMG) to evaluate whether visuomotor associations affect interpersonal motor resonance, a putative measure of mirror system activity. 18 participants underwent two TMS sessions exploring whether visuomotor associations established throughout one׳s lifespan, namely common movements and movements generated from one׳s own perspective, are associated with increased putative mirror system activity. Our results showed no overall difference in interpersonal motor resonance to common versus uncommon actions, or actions presented from an egocentric (self) versus an allocentric (other) perspective. We did, however, observe increased interpersonal motor resonance within the abductor digiti minimi (ADM) muscle in response to allocentric compared to egocentric movements. As the association model predicts stronger mirror system response to actions with stronger visuomotor associations, such as common movements and those presented from an egocentric perspective, our findings provide little evidence to support the association model.

Hidden Markov model neurons classification based on Mel-frequency cepstral coefficients

In neuroscience, the extracellular actions potentials of neurons are the most important signals, which are called spikes. However, a single extracellular electrode can capture spikes from more than one neuron. Spike sorting is an important task to diagnose various neural activities. The more we can understand neurons the more we can cure more neural diseases. The process of sorting these spikes is typically made in some steps which are detection, feature extraction and clustering. In this paper we propose to use the Mel-frequency cepstral coefficients (MFCC) to extract spike features associated with Hidden Markov model (HMM) in the clustering step. Our results show that using MFCC features can differentiate between spikes more clearly than the other feature extraction methods, and also using HMM as a clustering algorithm also yields a better sorting accuracy.