Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra)

The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography–mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERa and ERß). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERa. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17ß-estradiol (E2). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20–60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERa or ERß subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E2, not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERa-selective antagonism, similar to the ERa-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E2 by approximately 80% at 6¿×¿10-6 M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERa

Magnetotunneling spectroscopy of mesoscopic correlations in two-dimensional electron systems

An approach to experimentally exploring electronic correlation functions in mesoscopic regimes is proposed. The idea is to monitor the mesoscopic fluctuations of a tunneling current flowing between the two layers of a semiconductor double-quantum-well structure. From the dependence of these fluctuations on external parameters, such as in-plane or perpendicular magnetic fields, external bias voltages, etc., the temporal and spatial dependence of various prominent correlation functions of mesoscopic physics can be determined. Due to the absence of spatially localized external probes, the method provides a way to explore the interplay of interaction and localization effects in two-dimensional systems within a relatively unperturbed environment. We describe the theoretical background of the approach and quantitatively discuss the behavior of the current fluctuations in diffusive and ergodic regimes. The influence of both various interaction mechanisms and localization effects on the current is discussed. Finally a proposal is made on how, at least in principle, the method may be used to experimentally determine the relevant critical exponents of localization-delocalization transitions.Comment: 15 pages, 3 figures include

Slicing:A sustainable approach to structuring samples for analysis in long-term studies

The longitudinal study of populations is a core tool for understanding ecological and evolutionary processes. Long‐term studies typically collect samples repeatedly over individual lifetimes and across generations. These samples are then analysed in batches (e.g. qPCR plates) and clusters (i.e. group of batches) over time in the laboratory. However, these analyses are constrained by cross‐classified data structures introduced biologically or through experimental design. The separation of biological variation from the confounding among‐batch and among‐cluster variation is crucial, yet often ignored. The commonly used approaches to structuring samples for analysis, sequential and randomization, generate bias due to the non‐independence between time of collection and the batch and cluster they are analysed in. We propose a new sample structuring strategy, called slicing, designed to separate confounding among‐batch and among‐cluster variation from biological variation. Through simulations, we tested the statistical power and precision to detect within‐individual, between‐individual, year and cohort effects of this novel approach. Our slicing approach, whereby recently and previously collected samples are sequentially analysed in clusters together, enables the statistical separation of collection time and cluster effects by bridging clusters together, for which we provide a case study. Our simulations show, with reasonable slicing width and angle, similar precision and similar or greater statistical power to detect year, cohort, within‐ and between‐individual effects when samples are sliced across batches, compared with strategies that aggregate longitudinal samples or use randomized allocation. While the best approach to analysing long‐term datasets depends on the structure of the data and questions of interest, it is vital to account for confounding among‐cluster and batch variation. Our slicing approach is simple to apply and creates the necessary statistical independence of batch and cluster from environmental or biological variables of interest. Crucially, it allows sequential analysis of samples and flexible inclusion of current data in later analyses without completely confounding the analysis. Our approach maximizes the scientific value of every sample, as each will optimally contribute to unbiased statistical inference from the data. Slicing thereby maximizes the power of growing biobanks to address important ecological, epidemiological and evolutionary questions

Electronic and thermal sequential transport in metallic and superconducting two-junction arrays

The description of transport phenomena in devices consisting of arrays of tunnel junctions, and the experimental confirmation of these predictions is one of the great successes of mesoscopic physics. The aim of this paper is to give a self-consistent review of sequential transport processes in such devices, based on the so-called "orthodox" model. We calculate numerically the current-voltage (I-V) curves, the conductance versus bias voltage (G-V) curves, and the associated thermal transport in symmetric and asymmetric two-junction arrays such as Coulomb-blockade thermometers (CBTs), superconducting-insulator-normal-insulator-superconducting (SINIS) structures, and superconducting single-electron transistors (SETs). We investigate the behavior of these systems at the singularity-matching bias points, the dependence of microrefrigeration effects on the charging energy of the island, and the effect of a finite superconducting gap on Coulomb-blockade thermometry.Comment: 23 pages, 12 figures; Berlin (ISBN: 978-3-642-12069-5

From wrongdoing to imprisonment: Test of a causal-moral model

The authors tested a causal–moral model of punishment in which (a) causal attribution and moral responsibility are distinct precursors of punishment, and (b) dispositional attribution leads to blame which, in turn, determines imprisonment. Specifically, whereas severity of outcome impacts punishment directly, circumstances of the crime and the culture of the observers impact punishment through causal attribution and blame, respectively. In an experiment, Singaporeans and Americans read about a crime that (a) was committed intentionally or under an extenuating circumstance and (b) had low or severe outcome for the victim. They made dispositional attribution to, assigned blame to, and recommended imprisonment for the offender. Results supported the hypotheses and the causal–moral path model that specified a direct effect of severity of outcome, an indirect effect of country via blame, and the indirect effects of circumstance via dispositional attribution to blame on imprisonment

The primary cilium influences interleukin-1 beta-induced NF kappa B signalling by regulating IKK activity

AbstractThe primary cilium is an organelle acting as a master regulator of cellular signalling. We have previously shown that disruption of primary cilia assembly, through targeting intraflagellar transport, is associated with muted nitric oxide and prostaglandin responses to the inflammatory cytokine interleukin-1β (IL-1β). Here, we show that loss of the primary cilium disrupts specific molecular signalling events in cytosolic NFκB signalling. The induction of cyclooxygenase 2 (COX2) and inducible nitrous oxide synthase (iNOS) protein is abolished. Cells unable to assemble cilia exhibit unaffected activation of IκB kinase (IKK), but delayed and reduced degradation of IκB, due to diminished phosphorylation of inhibitor of kappa B (IκB) by IKK. This results in both delayed and reduced NFκB p65 nuclear translocation and nuclear transcript binding. We also demonstrate that heat shock protein 27 (hsp27), an established regulator of IKK, is localized to the ciliary axoneme and cellular levels are dramatically disrupted with loss of the primary cilium. These results suggest that the primary cilia compartment exerts influence over NFκB signalling. We propose that the cilium is a locality for regulation of the molecular events defining NFκB signalling events, tuning signalling as appropriate

Dealing Automatically with Exceptions by Introducing Specificity in ASP

Answer Set Programming (ASP), via normal logic programs, is known as a suitable framework for default reasoning since it offers both a valid formal model and operational systems. However, in front of a real world knowledge representation problem, it is not easy to represent information in this framework. That is why the present article proposed to deal with this issue by generating in an automatic way the suitable normal logic program from a compact representation of the information. This is done by using a method, based on specificity, that has been developed for default logic and which is adapted here to ASP both in theoretical and practical points of view

Effect of Sand and Wood-Shavings Bedding on the Behavior of Broiler Chickens

The purpose of this study was to determine the effect of 2 different bedding types, sand and wood shavings, on the behavior of broiler chickens. In experiment 1, 6 pens were divided down the center and bedded half with sand and half with wood shavings. Male broilers (10/pen) were observed by scan sampling at 5- or 12-min intervals throughout the 6-wk growth period during the morning (between 0800 to 0900 h), afternoon (1200 to 1500 h), and night (2300 to 0600 h). There was a significant behavior x substrate x week interaction during the day (P \u3c 0.0001) and at night (P \u3c 0.0002). Drinking, dustbathing, preening, and sitting increased in frequency on the sand side but decreased on the wood shavings side during the day, as did resting at night. In general, broilers performed a greater proportion of their total behavioral time budget on the sand (P \u3c 0.0001) as they aged. Broilers used the divider between the 2 bedding types to perch; perching behavior peaked during wk 4. In experiment 2, male broilers were housed in 8 pens (50 birds/pen) bedded only in sand or wood shavings. Bedding type had no effect on behavioral time budgets (P = 0.8946), although there were age-related changes in behavior on both bedding types. These results indicate that when given a choice, broilers increasingly performed many of their behaviors on sand, but if only one bedding type was provided they performed those behaviors with similar frequency on sand or wood shavings