Components of olive oil and chemoprevention of colorectal cancer

Olive oil contains a vast range of substances such as monounsaturated free fatty acids (e.g., oleic acid), hydrocarbon squalene, tocopherols, aroma components, and phenolic compounds. Higher consumption of olive oil is considered the hallmark of the traditional Mediterranean diet, which has been associated with low incidence and prevalence of cancer, including colorectal cancer. The anticancer properties of olive oil have been attributed to its high levels of monounsaturated fatty acids, squalene, tocopherols, and phenolic compounds. Nevertheless, there is a growing interest in studying the role of olive oil phenolics in carcinogenesis. This review aims to provide an overview of the relationship between olive oil phenolics and colorectal cancer, in particular summarizing the epidemiologic, in vitro, cellular, and animal studies on antioxidant and anticarcinogenic effects of olive oil phenolics.

Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries

Background: In rat middle cerebral and mesenteric arteries the KCa2.3 component of endothelium-dependent hyperpolarization (EDH) is lost following stimulation of thromboxane (TP) receptors, an effect that may contribute to the endothelial dysfunction associated with cardiovascular disease. In cerebral arteries, KCa2.3 loss is associated with NO synthase inhibition, but is restored if TP receptors are blocked. The Rho/Rho kinase pathway is central for TP signalling and statins indirectly inhibit this pathway. The possibility that Rho kinase inhibition and statins sustain KCa2.3 hyperpolarization was investigated in rat middle cerebral arteries (MCA). Methods: MCAs were mounted in a wire myograph. The PAR2 agonist, SLIGRL was used to stimulate EDH responses, assessed by simultaneous measurement of smooth muscle membrane potential and tension. TP expression was assessed with rt-PCR and immunofluorescence. Results: Immunofluorescence detected TP in the endothelial cell layer of MCA. Vasoconstriction to the TP agonist, U46619 was reduced by Rho kinase inhibition. TP receptor stimulation lead to loss of KCa2.3 mediated hyperpolarization, an effect that was reversed by Rho kinase inhibitors or simvastatin. KCa2.3 activity was lost in L-NAME-treated arteries, but was restored by Rho kinase inhibition or statin treatment. The restorative effect of simvastatin was blocked after incubation with geranylgeranyl-pyrophosphate to circumvent loss of isoprenylation. Conclusions: Rho/Rho kinase signalling following TP stimulation and L-NAME regulates endothelial cell KCa2.3 function. The ability of statins to prevent isoprenylation and perhaps inhibit of Rho restores/protects the input of KCa2.3 to EDH in the MCA, and represents a beneficial pleiotropic effect of statin treatment.

Identification of core and variable components of the Salmonella enterica subspecies I genome by microarray

We have performed microarray hybridization studies on 40 clinical isolates from 12 common serovars within Salmonella enterica subspecies I to identify the conserved chromosomal gene pool. We were able to separate the core invariant portion of the genome by a novel mathematical approach using a decision tree based on genes ranked by increasing variance. All genes within the core component were confirmed using available sequence and microarray information for S. enterica subspecies I strains. The majority of genes within the core component had conserved homologues in Escherichia coli K-12 strain MG1655. However, many genes present in the conserved set which were absent or highly divergent in K-12 had close homologues in pathogenic bacteria such as Shigella flexneri and Pseudomonas aeruginosa. Genes within previously established virulence determinants such as SPI1 to SPI5 were conserved. In addition several genes within SPI6, all of SPI9, and three fimbrial operons (fim, bcf, and stb) were conserved within all S. enterica strains included in this study. Although many phage and insertion sequence elements were missing from the core component, approximately half the pseudogenes present in S. enterica serovar Typhi were conserved. Furthermore, approximately half the genes conserved in the core set encoded hypothetical proteins. Separation of the core and variant gene sets within S. enterica subspecies I has offered fundamental biological insight into the genetic basis of phenotypic similarity and diversity across S. enterica subspecies I and shown how the core genome of these pathogens differs from the closely related E. coli K-12 laboratory strain.

Endosomes: a legitimate platform for the signaling train

Although long regarded as a conduit for the degradation or recycling of cell surface receptors, the endosomal system is also an essential site of signal transduction. Activated receptors accumulate in endosomes, and certain signaling components are exclusively localized to endosomes. Receptors can continue to transmit signals from endosomes that are different from those that arise from the plasma membrane, resulting in distinct physiological responses. Endosomal signaling is widespread in metazoans and plants, where it transmits signals for diverse receptor families that regulate essential processes including growth, differentiation and survival. Receptor signaling at endosomal membranes is tightly regulated by mechanisms that control agonist availability, receptor coupling to signaling machinery, and the subcellular localization of signaling components. Drugs that target mechanisms that initiate and terminate receptor signaling at the plasma membrane are widespread and effective treatments for disease. Selective disruption of receptor signaling in endosomes, which can be accomplished by targeting endosomal-specific signaling pathways or by selective delivery of drugs to the endosomal network, may provide novel therapies for disease.

Developing new components for variable flow distribution system modelling in TRNSYS

This study attempts to fill the existing gap in the simulation of variable flow distribution systems through developing new pressure governing components. These components are able to capture the actual ever-changing system performance curve in variable flow distribution systems together with the prediction of controversial issues such as starving, over-flow and the lack of controllability on the flow rate of different branches in a hydronic system. The performance of the proposed components is verified using a case study under design and off-design circumstances. Full integration of the new components within the TRNSYS simulation package is another advantage of this study, which makes it more applicable for designers in both the design and commissioning of hydronic systems.

Scale-selective verification of rainfall accumulations from high-resolution forecasts of convective events

The development of NWP models with grid spacing down to 1 km should produce more realistic forecasts of convective storms. However, greater realism does not necessarily mean more accurate precipitation forecasts. The rapid growth of errors on small scales in conjunction with preexisting errors on larger scales may limit the usefulness of such models. The purpose of this paper is to examine whether improved model resolution alone is able to produce more skillful precipitation forecasts on useful scales, and how the skill varies with spatial scale. A verification method will be described in which skill is determined from a comparison of rainfall forecasts with radar using fractional coverage over different sized areas. The Met Office Unified Model was run with grid spacings of 12, 4, and 1 km for 10 days in which convection occurred during the summers of 2003 and 2004. All forecasts were run from 12-km initial states for a clean comparison. The results show that the 1-km model was the most skillful over all but the smallest scales (approximately <10–15 km). A measure of acceptable skill was defined; this was attained by the 1-km model at scales around 40–70 km, some 10–20 km less than that of the 12-km model. The biggest improvement occurred for heavier, more localized rain, despite it being more difficult to predict. The 4-km model did not improve much on the 12-km model because of the difficulties of representing convection at that resolution, which was accentuated by the spinup from 12-km fields.

Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs

Flavonoids are low-molecular weight, aromatic compounds derived from fruits, vegetables, and other plant components. The consumption of these phytochemicals has been reported to be associated with reduced cardiovascular disease (CVD) risk, attributed to their anti-inflammatory, anti-proliferative, and anti-thrombotic actions. Flavonoids exert these effects by a number of mechanisms which include attenuation of kinase activity mediated at the cell-receptor level and/or within cells, and are characterized as broad-spectrum kinase inhibitors. Therefore, flavonoid therapy for CVD is potentially complex; the use of these compounds as molecular templates for the design of selective and potent small-molecule inhibitors may be a simpler approach to treat this condition. Flavonoids as templates for drug design are, however, poorly exploited despite the development of analogues based on the flavonol, isoflavonone, and isoflavanone subgroups. Further exploitation of this family of compounds is warranted due to a structural diversity that presents great scope for creating novel kinase inhibitors. The use of computational methodologies to define the flavonoid pharmacophore together with biological investigations of their effects on kinase activity, in appropriate cellular systems, is the current approach to characterize key structural features that will inform drug design. This focussed review highlights the potential of flavonoids to guide the design of clinically safer, more selective, and potent small-molecule inhibitors of cell signalling, applicable to anti-platelet therapy.

One-port de-embedding technique for the quasi-optical characterization of integrated components

We describe a one-port de-embedding technique suitable for the quasi-optical characterization of terahertz integrated components at frequencies beyond the operational range of most vector network analyzers. This technique is also suitable when the manufacturing of precision terminations to sufficiently fine tolerances for the application of a TRL de-embedding technique is not possible. The technique is based on vector reflection measurements of a series of easily realizable test pieces. A theoretical analysis is presented for the precision of the technique when implemented using a quasi-optical null-balanced bridge reflectometer. The analysis takes into account quantization effects in the linear and angular encoders associated with the balancing procedure, as well as source power and detector noise equivalent power. The precision in measuring waveguide characteristic impedance and attenuation using this de-embedding technique is further analyzed after taking into account changes in the power coupled due to axial, rotational, and lateral alignment errors between the device under test and the instruments' test port. The analysis is based on the propagation of errors after assuming imperfect coupling of two fundamental Gaussian beams. The required precision in repositioning the samples at the instruments' test-port is discussed. Quasi-optical measurements using the de-embedding process for a WR-8 adjustable precision short at 125 GHz are presented. The de-embedding methodology may be extended to allow the determination of S-parameters of arbitrary two-port junctions. The measurement technique proposed should prove most useful above 325 GHz where there is a lack of measurement standards.

Analysis of the variability of auditory brainstem response components through linear regression

(ABR) is of fundamental importance to the investiga- tion of the auditory system behavior, though its in- terpretation has a subjective nature because of the manual process employed in its study and the clinical experience required for its analysis. When analyzing the ABR, clinicians are often interested in the identi- fication of ABR signal components referred to as Jewett waves. In particular, the detection and study of the time when these waves occur (i.e., the wave la- tency) is a practical tool for the diagnosis of disorders affecting the auditory system. In this context, the aim of this research is to compare ABR manual/visual analysis provided by different examiners. Methods: The ABR data were collected from 10 normal-hearing subjects (5 men and 5 women, from 20 to 52 years). A total of 160 data samples were analyzed and a pair- wise comparison between four distinct examiners was executed. We carried out a statistical study aiming to identify significant differences between assessments provided by the examiners. For this, we used Linear Regression in conjunction with Bootstrap, as a me- thod for evaluating the relation between the responses given by the examiners. Results: The analysis sug- gests agreement among examiners however reveals differences between assessments of the variability of the waves. We quantified the magnitude of the ob- tained wave latency differences and 18% of the inves- tigated waves presented substantial differences (large and moderate) and of these 3.79% were considered not acceptable for the clinical practice. Conclusions: Our results characterize the variability of the manual analysis of ABR data and the necessity of establishing unified standards and protocols for the analysis of these data. These results may also contribute to the validation and development of automatic systems that are employed in the early diagnosis of hearing loss.

Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment

Background Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. Methods We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key “punishment” areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.

Credit and liquidity components of corporate CDS spreads

This paper investigates the role of credit and liquidity factors in explaining corporate CDS price changes during normal and crisis periods. We find that liquidity risk is more important than firm-specific credit risk regardless of market conditions. Moreover, in the period prior to the recent “Great Recession” credit risk plays no role in explaining CDS price changes. The dominance of liquidity effects casts serious doubts on the relevance of CDS price changes as an indicator of default risk dynamics. Our results show how multiple liquidity factors including firm specific and aggregate liquidity proxies as well as an asymmetric information measure are critical determinants of CDS price variations. In particular, the impact of informed traders on the CDS price increases when markets are characterised by higher uncertainty, which supports concerns of insider trading during the crisis.

Impact of probiotics, prebiotics and synbiotics on lipid metabolism in humans

Public health strategies for reducing the risk of coronary heart disease have focused on lowering plasma lipids, particularly cholesterol levels, with recent studies also highlighting triacylglycerol (TAG) as an important modifiable risk factor. One approach is to supplement the diet with probiotics, prebiotics or synbiotics. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Putative health benefits include improved resistance to gastrointestinal infections, reduction in lipid levels and stimulation of the immune system. Prebiotics are selectively fermented dietary components that are aimed at improving host health through selective fermentation by the gut microbiota, such as bifidobacteria and lactobacilli. Animal studies have shown prebiotics to markedly reduce circulating TAG and to a lesser extent cholesterol concentrations, with favourable but inconsistent findings with respect to changes in lipid levels in human studies. Here we provide an overview of the effects, and possible mechanisms, of probiotics, prebiotics and synbiotics (combination of a probiotic and prebiotic) on circulating lipeamia in humans.

Dissociating between object affordances and spatial compatibility effects using early response components

Perception and action are tightly linked: objects may be perceived not only in terms of visual features, but also in terms of possibilities for action. Previous studies showed that when a centrally located object has a salient graspable feature (e.g., a handle), it facilitates motor responses corresponding with the feature's position. However, such so-called affordance effects have been criticized as resulting from spatial compatibility effects, due to the visual asymmetry created by the graspable feature, irrespective of any affordances. In order to dissociate between affordance and spatial compatibility effects, we asked participants to perform a simple reaction-time task to typically graspable and non-graspable objects with similar visual features (e.g., lollipop and stop sign). Responses were measured using either electromyography (EMG) on proximal arm muscles during reaching-like movements, or with finger key-presses. In both EMG and button press measurements, participants responded faster when the object was either presented in the same location as the responding hand, or was affordable, resulting in significant and independent spatial compatibility and affordance effects, but no interaction. Furthermore, while the spatial compatibility effect was present from the earliest stages of movement preparation and throughout the different stages of movement execution, the affordance effect was restricted to the early stages of movement execution. Finally, we tested a small group of unilateral arm amputees using EMG, and found residual spatial compatibility but no affordance, suggesting that spatial compatibility effects do not necessarily rely on individuals’ available affordances. Our results show dissociation between affordance and spatial compatibility effects, and suggest that rather than evoking the specific motor action most suitable for interaction with the viewed object, graspable objects prompt the motor system in a general, body-part independent fashion

Effect of disease-selective predation on prey infected by contact and external sources

We propose and analyze a simple mathematical model for susceptible prey (S)–infected prey (I)–predator (P) interaction, where the susceptible prey population (S) is infected directly from external sources as well as through contact with infected class (I) and the predator completely avoids consuming the infected prey. The model is analyzed to obtain different thresholds of the key parameters under which the system exhibits stability around the biologically feasible equilibria. Through numerical simulations we display the effects of external infection and the infection through contact on the system dynamics in the absence as well as in the presence of the predator. We compare the system dynamics when infection occurs only through contact, with that when it occurs through contact and external sources. Our analysis demonstrates that under a disease-selective predation, stability and oscillations of the system is determined by two key parameters: the external infection rate and the force of infection through contact. Due to the introduction of external infection, the predator and the prey population show limit-cycle oscillations over a range parametric values. We suggest that while predicting the dynamics of such an eco-epidemiological system, the modes of infection and the infection rates might be carefully investigated.