Synthesis, crystal structures, magnetic properties and catecholase activity of double phenoxido-bridged penta-coordinated dinuclear nickel(II) complexes derived from reduced Schiff-base ligands: mechanistic inference of catecholase activity

Three double phenoxido-bridged dinuclear nickel(II) complexes, namely [Ni-2(L-1)(2)(NCS)(2)] (1), [Ni-2(L-2)(2)(NCS)(2)] (2), and [Ni-2(L-3)(2)(NCS)(2)] (3) have been synthesized using the reduced tridentate Schiff-base ligands 2-[1-(3-methylamino-propylamino)-ethyl]-phenol (HL1), 2-[1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL2), and 2-[1-(3-dimethylarnino-propylamino)-ethyl]-phenol (HL3), respectively. The coordination compounds have been characterized by X-ray structural analyses, magnetic-susceptibility measurements, and various spectroscopic methods. In all complexes, the nickel(II) ions are penta-coordinated in a square-pyramidal environment, which is severely distorted in the case of 1 (Addison parameter tau = 0.47) and 3 (tau = 0.29), while it is almost perfect for 2 (tau = 0.03). This arrangement leads to relatively strong antiferromagnetic interactions between the Ni(II) (S = 1) metal centers as mediated by double phenoxido bridges (with J values of -23.32 (1), -35.45 (2), and -34.02 (3) cm(3) K mol(-1), in the convention H = -2JS(1)S(2)). The catalytic activity of these Ni compounds has been investigated for the aerial oxidation of 3,5-di-tert-butylcatechol. Kinetic data analysis following Michaelis-Menten treatment reveals that the catecholase activity of the complexes is influenced by the flexibility of the ligand and also by the geometry around the metal ion. Electrospray ionization mass spectroscopy (ESI-MS) studies (in the positive mode) have been performed for all the coordination compounds in the presence of 3,5-DTBC to characterize potential complex-substrate intermediates. The mass-spectrometry data, corroborated by electron paramagnetic resonance (EPR) measurements, suggest that the metal centers are involved in the catecholase activity exhibited by the complexes.

Cis–trans isomerism in diphenoxido bridged dicopper complexes: role of crystallized water to stabilize the cis isomer, variation in magnetic properties and conversion of both into a trinuclear species

The trans-[Cu2L2Cl2] (1), and cis-[Cu2L2Cl2]·H2O (2) isomers of a diphenoxido bridged Cu2O2 core have been synthesized using a tridentate reduced Schiff base ligand 2-[(2-dimethylamino-ethylamino)-methyl]-phenol. The geometry around Cu(II) is intermediate between square pyramid and trigonal bipyramid (Addison parameter, tau = 0.463) in 1 but nearly square pyramidal (tau = 0.049) in 2. The chloride ions are coordinated to Cu(II) and are trans oriented in 1 but cis oriented in 2. Both isomers have been optimized using density functional theory (DFT) calculations and it is found that the trans isomer is 7.2 kcal mol(-1) more favorable than the cis isomer. However, the hydrogen bonding interaction of crystallized water molecule with chloride ions compensates for the energy difference and stabilizes the cis isomer. Both complexes have been converted to a very rare phenoxido-azido bridged trinuclear species, [Cu3L2(mu(1,1)-N-3)(2)(H2O)(2)(ClO4)(2)] (3) which has also been characterized structurally. All the complexes are antiferromagnetically coupled but the magnitude of the coupling constants are significantly different (J = -156.60, -652.31, and -31.54 cm(-1) for 1, 2, and 3 respectively). Density functional theory (DFT) calculations have also been performed to gain further insight into the qualitative theoretical interpretation on the overall magnetic behavior of the complexes.

A new tetranuclear copper(II) complex with oximate bridges: structure, magnetic properties and DFT study

A new tetranuclear complex, [Cu4L4](ClO4)4·2H2O (1), has been synthesized from the self-assembly of copper(II) perchlorate and the tridentate Schiff base ligand (2E,3E)-3-(2-aminopropylimino) butan-2-one oxime (HL). Single-crystal X-ray diffraction studies reveal that complex 1 consists of a Cu4(NO)4 core where the four copper(II) centers having square pyramidal environment are arranged in a distorted tetrahedral geometry. They are linked together by a rare bridging mode (μ3-η1,η2,η1) of oximato ligands. Analysis of magnetic susceptibility data indicates moderate antiferromagnetic (J1 = −48 cm−1, J2 = −40 cm−1 and J3 = −52 cm−1) exchange interaction through σ-superexchange pathways (in-plane bridging) of the oxime group. Theoretical calculations based on DFT technique have been used to obtain the energy states of different spin configurations and estimate the coupling constants and to understand the exact magnetic exchange pathways.

Dynamical control of the mesosphere by orographic and non-orographic gravity wave drag during the extended northern winters of 2006 and 2009

A version of the Canadian Middle Atmosphere Model (CMAM) that is nudged toward reanalysis data up to 1 hPa is used to examine the impacts of parameterized orographic and non-orographic gravity wave drag (OGWD and NGWD) on the zonal-mean circulation of the mesosphere during the extended northern winters of 2006 and 2009 when there were two large stratospheric sudden warmings. The simulations are compared to Aura Microwave Limb Sounder (MLS) observations of mesospheric temperature, carbon monoxide (CO) and derived zonal winds. The control simulation, which uses both OGWD and NGWD, is shown to be in good agreement with MLS. The impacts of OGWD and NGWD are assessed using simulations in which those sources of wave drag are removed. In the absence of OGWD the mesospheric zonal winds in the months preceding the warmings are too strong, causing increased mesospheric NGWD, which drives excessive downwelling, resulting in overly large lower mesospheric values of CO prior to the warming. NGWD is found to be most important following the warmings when the underlying westerlies are too weak to allow much vertical propagation of the orographic gravity waves to the mesosphere. NGWD is primarily responsible for driving the circulation that results in the descent of CO from the thermosphere following the warmings. Zonal mean mesospheric winds and temperatures in all simulations are shown to be strongly constrained by (i.e. slaved to) the stratosphere. Finally, it is demonstrated that the responses to OGWD and NGWD are non-additive due to their dependence and influence on the background winds and temperatures.

Self-ratings and observer-ratings of social skill: a manipulation of state social anxiety in anxious and non-anxious children

The role of state and trait anxiety on observer ratings of social skill and negatively biased self-perception of social skill was examined. Participants were aged between 7 and 13 years (mean=9.65; sd=1.77; N=102), 47 had a current anxiety diagnosis and 55 were non-anxious controls. Participants were randomly allocated to a high or low anxiety condition and asked to complete social tasks. Task instructions were adjusted across conditions to manipulate participants’ state anxiety. Observers rated anxious participants as having poorer social skills than non-anxious controls but there was no evidence that anxious participants exhibited a negative self-perception bias, relative to controls. However, as participants’ ratings of state anxiety increased, their perception of their performance became more negatively biased. The results suggest that anxious children may exhibit real impairments in social skill and that high levels of state anxiety can lead to biased judgements of social skills in anxious and non-anxious children.

Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease

Huntingtin (Htt) protein interacts with many transcriptional regulators, with widespread disruption to the transcriptome in Huntington's disease (HD) brought about by altered interactions with the mutant Htt (muHtt) protein. Repressor Element-1 Silencing Transcription Factor (REST) is a repressor whose association with Htt in the cytoplasm is disrupted in HD, leading to increased nuclear REST and concomitant repression of several neuronal-specific genes, including brain-derived neurotrophic factor (Bdnf). Here, we explored a wide set of HD dysregulated genes to identify direct REST targets whose expression is altered in a cellular model of HD but that can be rescued by knock-down of REST activity. We found many direct REST target genes encoding proteins important for nervous system development, including a cohort involved in synaptic transmission, at least two of which can be rescued at the protein level by REST knock-down. We also identified several microRNAs (miRNAs) whose aberrant repression is directly mediated by REST, including miR-137, which has not previously been shown to be a direct REST target in mouse. These data provide evidence of the contribution of inappropriate REST-mediated transcriptional repression to the widespread changes in coding and non-coding gene expression in a cellular model of HD that may affect normal neuronal function and survival.

Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease

HD (Huntington's disease) is a late onset heritable neurodegenerative disorder that is characterized by neuronal dysfunction and death, particularly in the cerebral cortex and medium spiny neurons of the striatum. This is followed by progressive chorea, dementia and emotional dysfunction, eventually resulting in death. HD is caused by an expanded CAG repeat in the first exon of the HD gene that results in an abnormally elongated polyQ (polyglutamine) tract in its protein product, Htt (Huntingtin). Wild-type Htt is largely cytoplasmic; however, in HD, proteolytic N-terminal fragments of Htt form insoluble deposits in both the cytoplasm and nucleus, provoking the idea that mutHtt (mutant Htt) causes transcriptional dysfunction. While a number of specific transcription factors and co-factors have been proposed as mediators of mutHtt toxicity, the causal relationship between these Htt/transcription factor interactions and HD pathology remains unknown. Previous work has highlighted REST [RE1 (repressor element 1)-silencing transcription factor] as one such transcription factor. REST is a master regulator of neuronal genes, repressing their expression. Many of its direct target genes are known or suspected to have a role in HD pathogenesis, including BDNF (brain-derived neurotrophic factor). Recent evidence has also shown that REST regulates transcription of regulatory miRNAs (microRNAs), many of which are known to regulate neuronal gene expression and are dysregulated in HD. Thus repression of miRNAs constitutes a second, indirect mechanism by which REST can alter the neuronal transcriptome in HD. We will describe the evidence that disruption to the REST regulon brought about by a loss of interaction between REST and mutHtt may be a key contributory factor in the widespread dysregulation of gene expression in HD.

Linear and non-linear transmission of equity return volatility: evidence from the US, Japan and Australia

This paper models the transmission of shocks between the US, Japanese and Australian equity markets. Tests for the existence of linear and non-linear transmission of volatility across the markets are performed using parametric and non-parametric techniques. In particular the size and sign of return innovations are important factors in determining the degree of spillovers in volatility. It is found that a multivariate asymmetric GARCH formulation can explain almost all of the non-linear causality between markets. These results have important implications for the construction of models and forecasts of international equity returns.

Linear and non-linear (non-)forecastability of high-frequency exchange rates

This paper forecasts Daily Sterling exchange rate returns using various naive, linear and non-linear univariate time-series models. The accuracy of the forecasts is evaluated using mean squared error and sign prediction criteria. These show only a very modest improvement over forecasts generated by a random walk model. The Pesaran–Timmerman test and a comparison with forecasts generated artificially shows that even the best models have no evidence of market timing ability.

Applications of micromorphology to understanding activity areas and site formation processes in experimental hut floors

Experimental buildings at Butser Ancient Farm and St. Fagans (UK) and Lejre (Denmark) were sampled to investigate micromorphology of known activity areas, to contribute to our understanding of the internal use of space in excavated buildings and formation processes of house floor deposits. The experimental buildings provided important information relating to activity residues and sediments over the 16 years that the buildings were in use. Specifically, these results contribute to our understanding of the routes and cycles for transportation of materials in occupation contexts, which can be used to inform archaeological studies. It has been possible to identify internal ‘hot spots’ within the buildings for the deposition of activity residues and for the formation of specific deposit types. Analysis also highlighted postdepositional alterations occurring in internal occupation deposits, which has provided a means of identifying roofed and unroofed spaces in the archaeological record.

Use of virulence determinants and seropathotypes to distinguish high- and low-risk Escherichia coli O157 and non-O157 isolates from Europe

The presence of 10 virulence genes was examined using polymerase chain reaction (PCR) in 365 European O157 and non-O157 Escherichia coli isolates associated with verotoxin production. Strain-specific PCR data were analysed using hierarchical clustering. The resulting dendrogram clearly separated O157 from non-O157 strains. The former clustered typical high-risk seropathotype (SPT) A strains from all regions, including Sweden and Spain, which were homogenous by Cramer's V statistic, and strains with less typical O157 features mostly from Hungary. The non-O157 strains divided into a high-risk SPTB harbouring O26, O111 and O103 strains, a group pathogenic to pigs, and a group with few virulence genes other than for verotoxin. The data demonstrate SPT designation and selected PCR separated verotoxigenic E. coli of high and low risk to humans; although more virulence genes or pulsed-field gel electrophoresis will need to be included to separate high-risk strains further for epidemiological tracing.