Observed trends and teleconnections of the Siberian high: A recently declining center of action

This study investigates variability in the intensity of the wintertime Siberian high (SH) by defining a robust SH index (SHI) and correlating it with selected meteorological fields and teleconnection indices. A dramatic trend of -2.5 hPa decade(-1) has been found in the SHI between 1978 and 2001 with unprecedented (since 1871) low values of the SHI. The weakening of the SH has been confirmed by analyzing different historical gridded analyses and individual station observations of sea level pressure (SLP) and excluding possible effects from the conversion of surface pressure to SLP. SHI correlation maps with various meteorological fields show that SH impacts on circulation and temperature patterns extend far outside the SH source area extending from the Arctic to the tropical Pacific. Advection of warm air from eastern Europe has been identified as the main mechanism causing milder than normal conditions over the Kara and Laptev Seas in association with a strong SH. Despite the strong impacts of the variability in the SH on climatic variability across the Northern Hemisphere, correlations between the SHI and the main teleconnection indices of the Northern Hemisphere are weak. Regression analysis has shown that teleconnection indices are not able to reproduce the interannual variability and trends in the SH. The inclusion of regional surface temperature in the regression model provides closer agreement between the original and reconstructed SHI.

Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.

We developed a family of polymer-drug conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.

Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats

The recent discovery that vitamin E (VE) regulates gene activity at the transcriptional level indicates that VE may exert part of its biological effects by mechanisms which may be independent of its well-recognised antioxidant function. The objective of this study was the identification of hepatic vitamin E-sensitive genes and examination of the effects of VE on their corresponding biological endpoints. Two groups of male rats were randomly assigned to either a VE-sufficient diet or to a control diet deficient in VE for 290 days. High-density oligonucleotide microarrays comprising over 7000 genes were used to assess the transcriptional response of the liver. Differential gene expression was monitored over a period of 9 months, at four different time-points, and rats were individually profiled. This experimental strategy identified several VE-sensitive genes, which were chronically altered by dietary VE. VE supplementation down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase was significantly up-regulated. Measurement of the corresponding biological endpoints such as activated partial thromboplastin time, plasma dihydrotestosterone and hepatic glutathione substantiated the gene chip data which indicated that dietary VE plays an important role in a range of metabolic processes within the liver. (C) 2004 Elsevier B.V. All rights reserved.

Action preparation helps and hinders perception of action.

Several theories of the mechanisms linking perception and action require that the links are bidirectional, but there is a lack of consensus on the effects that action has on perception. We investigated this by measuring visual event-related brain potentials to observed hand actions while participants prepared responses that were spatially compatible (e.g., both were on the left side of the body) or incompatible and action type compatible (e.g., both were finger taps) or incompatible, with observed actions. An early enhanced processing of spatially compatible stimuli was observed, which is likely due to spatial attention. This was followed by an attenuation of processing for both spatially and action type compatible stimuli, likely to be driven by efference copy signals that attenuate processing of predicted sensory consequences of actions. Attenuation was not response-modality specific; it was found for manual stimuli when participants prepared manual and vocal responses, in line with the hypothesis that action control is hierarchically organized. These results indicate that spatial attention and forward model prediction mechanisms have opposite, but temporally distinct, effects on perception. This hypothesis can explain the inconsistency of recent findings on action-perception links and thereby supports the view that sensorimotor links are bidirectional. Such effects of action on perception are likely to be crucial, not only for the control of our own actions but also in sociocultural interaction, allowing us to predict the reactions of others to our own actions.

Titanocene anticancer complexes and their binding mode of action to human serum albumin: a computational study

Due to the pivotal role played by human serum albumin (HSA) in the transport and cytotoxicity of titanocene complexes, a docking study has been performed on a selected set of titanocene complexes to aid in the current understanding of the potential mode of action of these titanocenes upon binding HSA. Analysis of the docking results has revealed potential binding at the known drug binding sites in HSA and has provided some explanation for the specificity and subsequent cytotoxicity of these titanocenes. Additionally, a new alternative binding site for these titanocenes has been postulated.

Olive leaf phenolics and cardiovascular risk reduction: Physiological effects and mechanisms of action

Olive oil, an important component of the Mediterranean diet, is rich in polyphenols and is known to possess positive health effects relative to other dietary fats. In addition, the leaves of the olive plant (Olea europaea) contain similar phenolics (oleuropein, luteolin-7-glucoside, apigenin-7-glucoside, verbascoside and hydroxytyrosol) to those of olives and olive oil, although at higher concentrations. For example, the most abundant is the secoiridoid, oleuropein, representing 1–14% of olive leaf weight vs. 0.005–0.12% in olive oil. Although currently considered a waste product of the olive oil industry, recent research has suggested beneficial effects of phenolic-rich olive leaf extracts (OLE) in modifying cardiovascular risk biomarkers such as blood pressure, hyperglycaemia, oxidative stress and inflammation, as well as improving vascular function and lipid profiles. Despite this, data regarding the biological actions of OLE has mostly derived from animal, in vitro and ex vivo studies, with limited evidence deriving from human trials. Although the absorption and metabolism of olive oil phenolics has been investigated, less is known about the bioavailability of phenolics from OLE, limiting the interpretation of existing in vitro and ex vivo data. The current review will begin by describing the phenolic composition of olive leaves in comparison with that of the better studied olive oil. It will then review the effects of OLE on cardiovascular risk factors, covering both animal and human studies and will end by considering potential mechanisms of action

The creativity of action: Property, Kin and the social in African artisanal mining

Analyses of neo-liberal change in African mining tend to frame discussion through the lens of an overarching structural perspective. Far less attention has been paid to the way change is enacted within social relations in mining communities. To this end, our chapter considers how development in the Tanzanian mineral sector transforms people’s relationships and stimulates new iterations of power and agency within local trajectories of development, focusing on the case of artisanal gold mining in Mgusu village in Geita region, Tanzania. The aim is to trace how neo-liberal change configures market rationality and property relations in ways that can fundamentally alter social relationships within the local community, occupational groups and families, raising both opportunities for wealth accumulation and the potential to entrench poverty. The creative action involved in these processes generates new associational ties and repertoires of practice, as miners’ respond to change and the need to protect their livelihoods.

Effects of action observation on corticospinal excitability: muscle specificity, direction, and timing of the mirror response

Many human behaviours and pathologies have been attributed to the putative mirror neuron system, a neural system that is active during both the observation and execution of actions. While there are now a very large number of papers on the mirror neuron system, variations in the methods and analyses employed by researchers mean that the basic characteristics of the mirror response are not clear. This review focuses on three important aspects of the mirror response, as measured by modulations in corticospinal excitability: (1) muscle specificity, (2) direction, and (3) timing of modulation. We focus mainly on electromyographic (EMG) data gathered following single-pulse transcranial magnetic stimulation (TMS), because this method provides precise information regarding these three aspects of the response. Data from paired-pulse TMS paradigms and peripheral nerve stimulation (PNS) are also considered when we discuss the possible mechanisms underlying the mirror response. In this systematic review of the literature, we examine the findings of 85 TMS and PNS studies of the human mirror response, and consider the limitations and advantages of the different methodological approaches these have adopted in relation to discrepancies between their findings. We conclude by proposing a testable model of how action observation modulates corticospinal excitability in humans. Specifically, we propose that action observation elicits an early, non-specific facilitation of corticospinal excitability (at around 90 ms from action onset), followed by a later modulation of activity specific to the muscles involved in the observed action (from around 200 ms). Testing this model will greatly advance our understanding of the mirror mechanism and provide a more stable grounding on which to base inferences about its role in human behaviour.

A review of the cognitive effects observed in humans following acute supplementation with flavonoids, and their associated mechanisms of action

Flavonoids are polyphenolic compounds found in varying concentrations in many plant-based foods. Recent studies suggest that flavonoids can be beneficial to both cognitive and physiological health. Long term flavonoid supplementation over a period of weeks or months has been extensively investigated and reviewed, particularly with respect to cognitive ageing and neurodegenerative disease. Significantly less focus has been directed towards the short term effects of single doses of flavonoids on cognition. Here, we review 21 such studies with particular emphasis on the subclass and dose of flavonoids administered, the cognitive domains affected by flavonoid supplementation, and the effect size of the response. The emerging evidence suggests that flavonoids may be beneficial to attention, working memory, and psychomotor processing speed in a general population. Episodic memory effects are less well defined and may be restricted to child or older adult populations. The evidence also points towards a dose-dependent effect of flavonoids, but the physiological mechanisms of action remain unclear. Overall, there is encouraging evidence that flavonoid supplementation can benefit cognitive outcomes within an acute time frame of 0–6 h. But larger studies, combining cognitive and physiological measures, are needed to strengthen the evidence base.

MEASUREMENT AND MODELING OF THE TOXICITY OF BINARY MIXTURES IN THE NEMATODE CAENORHABDITIS ELEGANS-A TEST OF INDEPENDENT ACTION

Ecological risk assessments must increasingly consider the effects of chemical mixtures on the environment as anthropogenic pollution continues to grow in complexity. Yet testing every possible mixture combination is impractical and unfeasible; thus, there is an urgent need for models that can accurately predict mixture toxicity from single-compound data. Currently, two models are frequently used to predict mixture toxicity from single-compound data: Concentration addition and independent action (IA). The accuracy of the predictions generated by these models is currently debated and needs to be resolved before their use in risk assessments can be fully justified. The present study addresses this issue by determining whether the IA model adequately described the toxicity of binary mixtures of five pesticides and other environmental contaminants (cadmium, chlorpyrifos, diuron, nickel, and prochloraz) each with dissimilar modes of action on the reproduction of the nematode Caenorhabditis elegans. In three out of 10 cases, the IA model failed to describe mixture toxicity adequately with significant or antagonism being observed. In a further three cases, there was an indication of synergy, antagonism, and effect-level-dependent deviations, respectively, but these were not statistically significant. The extent of the significant deviations that were found varied, but all were such that the predicted percentage effect seen on reproductive output would have been wrong by 18 to 35% (i.e., the effect concentration expected to cause a 50% effect led to an 85% effect). The presence of such a high number and variety of deviations has important implications for the use of existing mixture toxicity models for risk assessments, especially where all or part of the deviation is synergistic.

Self-defence: A state of mind for states?

This paper focuses upon a comparatively overlooked issue with regard to the scope of self-defence in international law: whether the subjective ‘psychological’ positions of the states concerned in a dispute involving the use force have any impact upon the lawfulness of an action avowedly taken in self-defence. There exists a long standing conception that the motives of a state responding in self-defence are relevant to the lawfulness of that response. The purity (or impurity) of a state's motive forms the basis of a distinction for many writers between a lawful self-defence action and an unlawful armed reprisal. Similarly, in recent decisions of the ICJ, the implication has been that the subjective intention of the attacking state may be relevant to the question of whether the attack perpetrated by that state can trigger the right of self-defence. The conclusion is reached here that the lawfulness of an avowed self-defence action should be premised upon objective criteria alone. Moreover, this reflects the law as it is in fact applied in practice. It is argued that the subjective ‘psychological’ position of either the responding or attacking state has no place in the final analysis of whether an action in self-defence was lawful or unlawful.