Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene 1-3.

BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.

Repressor element 1 silencing transcription factor couples loss of pluripotency with neural induction and neural differentiation

Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory program and reciprocal activation of the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie maintenance of pluripotency are partially characterized whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (repressor element 1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors and more recently, and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Furthermore, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes, and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation.

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB 1 receptor-independent mechanism

BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB 1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg −1 ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB 1 receptors was evaluated using displacement binding assays. KEY RESULTS CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg −1 ) and audiogenic seizure models (≥87 mg·kg −1 ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg −1 ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ 9 -tetrahydrocannabinol and Δ 9 -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB 1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB 1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

‘Getting known’: Beckett, Ireland and the creative industries

In the context of national and global trends of producing Beckett’s work, this essay will investigate recent productions of Beckett’s drama which originate in Ireland and tour internationally, examining how these relate to the concept of national identity and its marketability, as well the conceptual and material spaces provided by large-scale festival events. In the last few months, Pan Pan has toured its production of All that Fall from Dublin to the Beckett festival in Enniskillen to New York’s BAM. The Gate Theatre, always a powerhouse of Beckett productions, continues its revival of Barry McGovern’s adaptation of Watt; after the Edinburgh festival, the show will play London’s Barbican in March 2013. While originating in Ireland, these productions – those of the Gate in particular – have an international, as well as domestic, appeal. Examining these and forthcoming Gate productions, I query to what extent a theatre company’s cultural origins and international profile may create a perceived sense of authenticity or definitiveness among critical discourses at ‘home’ and abroad, and how such markers of identity are utilized by the marketing strategies which surround these productions. This article will interrogate the potential convergence of the globalized branding of both Beckett’s work and Irish identity, drawing on the writings of Bourdieu to elucidate how identity may be converted into economic and cultural capital, as well as examining the role that the festival event plays in this process.

No Haus Like Bau

The project consists of a live performance taking the 2005 IKEA riot as the starting point for a speculative history of a fictional future, culminating in a choreographed re-enactment of the original event. It is accompanied by a film series explores the possibility of collective action emerging from the capitalist relations inherent in the consumer riot. The performance, staged at the Berlin Biennale, continues this research into re-enactment and post-1989 politics, using a stage set made of flatpack furniture. Using the aesthetics of Modernism and the avant garde, the project transposes early twentieth century utopian ideology to a present day setting where mass uprisings are motivated by cheap commodities. By re-evaluating biomechanics and Bauhaus theatre theory, these explorations of consumerism and revolution propose that the mechanized movement developed in conjunction with industrial labour survives as a historical re-enactment in the wake of manufacturing work in the west. In the absence of a visual language apt to the contemporary, No Haus Like Bau uses re-enactment as a retrogarde tactic. Its purpose on the one hand is to invoke trajectories for alternate futures that never materialized at an originary moment. On the other hand, the clash of past forms with present content serves to accentuate the historical changes that have thrown into question these forms. Rather than reflecting the present, the projection of the past into a fictional future aims to destabilize the dominant narrative that suggests the current configuration of art, politics and human nature has always been this way. The project has been widely exhibited internationally and supported by Film London and Arts Council England. A theoretical essay on re-enactment as a strategy for performance has been published in Art Papers and in Memory [MIT]. The project also formed the basis of a solo exhibition at Te Tuhi Art Centre, Auckland.

Forecast convergence score: a forecaster's approach to analysing hydro-meteorological forecast systems.

In this paper the properties of a hydro-meteorological forecasting system for forecasting river flows have been analysed using a probabilistic forecast convergence score (FCS). The focus on fixed event forecasts provides a forecaster's approach to system behaviour and adds an important perspective to the suite of forecast verification tools commonly used in this field. A low FCS indicates a more consistent forecast. It can be demonstrated that the FCS annual maximum decreases over the last 10 years. With lead time, the FCS of the ensemble forecast decreases whereas the control and high resolution forecast increase. The FCS is influenced by the lead time, threshold and catchment size and location. It indicates that one should use seasonality based decision rules to issue flood warnings.

The processing of number and gender agreement in Spanish: an event related potential investigation of the effects of structural distance

Previous research suggests that the processing of agreement is affected by the distance between the agreeing elements. However, the unique contribution of structural distance (number of intervening syntactic phrases) to the processing of agreement remains an open question, since previous investigations do not tease apart structural and linear distance (number of intervening words). We used event related potentials (ERPs) to examine the extent to which structural distance impacts the processing of Spanish number and gender agreement. Violations were realized both within the phrase and across the phrase. Across both levels of structural distance, linear distance was kept constant, as was the syntactic category of the agreeing elements. Number and gender agreement violations elicited a robust P600 between 400 and 900ms, a component associated with morphosyntactic processing. No amplitude differences were observed between number and gender violations, suggesting that the two features are processed similarly at the brain level. Within-phrase agreement yielded more positive waveforms than across-phrase agreement, both for agreement violations and for grammatical sentences (no agreement by distance interaction). These effects can be interpreted as evidence that structural distance impacts the establishment of agreement overall, consistent with sentence processing models which predict that hierarchical structure impacts the processing of syntactic dependencies. However, due to the lack of an agreement by distance interaction, the possibility cannot be ruled out that these effects are driven by differences in syntactic predictability between the within-phrase and across-phrase configurations, notably the fact that the syntactic category of the critical word was more predictable in the within-phrase conditions.

Examining second language development using event-related potentials: a cross-sectional study on the processing of gender and number agreement

This cross-sectional study examines the role of L1-L2 differences and structural distance in the processing of gender and number agreement by English-speaking learners of Spanish at three different levels of proficiency. Preliminary results show that differences between the L1 and L2 impact L2 development, as sensitivity to gender agreement violations, as opposed to number agreement violations, emerges only in learners at advanced levels of proficiency. Results also show that the establishment of agreement dependencies is impacted by the structural distance between the agreeing elements for native speakers and for learners at intermediate and advanced levels of proficiency but not for low proficiency. The overall pattern of results suggests that the linguistic factors examined here impact development but do not constrain ultimate attainment; for advanced learners, results suggest that second language processing is qualitatively similar to native processing.

Individual differences and the role of the L1 in L2 processing: an ERP investigation

This study used ERP (event-related potentials) to examine both the role of the L1 and the role of individual differences in the processing of agreement violations. Theories of L2 acquisition differ with regard to whether or not native-like acquisition of L2 features is possible (Schwartz and Sprouse, 1994, 1996; Tsimpli and Mastropavlou, 2007), and the results of previous ERP studies are inconsistent when it comes to whether or not native-like processing is observed in response to L2 agreement violations (e.g., Sabourin, 2003; Tokowicz and MacWhinney, 2005). Furthermore, studies of learners in early stages of L2 acquisition have found variability in the emergence of native-like responses (e.g., McLaughlin et al., 2010; Tanner et al., 2009), but sources of variability have not been investigated. The current study examines responses to gender and number agreement violations in English-speaking learners of Spanish (n=24). Stimuli targeted agreement in three conditions: subject-verb agreement (el barco flota/*flotan), which is similar in Spanish and English; number agreement on adjectival predicates (la isla rocosa/*rocosas), a context in which agreement is not instantiated in English; and gender agreement on adjectival predicates (la isla rocosa/*rocoso), which is unique to Spanish. Grammaticality judgments and ERP responses were also tested for correlations with aptitude scores on the Modern Languages Aptitude Test (MLAT; Carroll and Sapon, 1959) and the Raven Advanced Progressive Matrices (Raven, 1965). Results are in line with theories that claim native-like processing is acquirable, since learners demonstrated similar ERP responses to a control group of native Spanish-speakers (n=8) with regard to all three agreement types. Additionally, the MLAT (but not the Raven) was significantly correlated with sensitivity to number violations, both in terms of grammaticality judgments and ERP amplitudes, indicating a role for verbal but not nonverbal aptitude in L2 processing.

Robust evaluation of fixed-event forecast rationality

In this paper we introduce a new testing procedure for evaluating the rationality of fixed-event forecasts based on a pseudo-maximum likelihood estimator. The procedure is designed to be robust to departures in the normality assumption. A model is introduced to show that such departures are likely when forecasters experience a credibility loss when they make large changes to their forecasts. The test is illustrated using monthly fixed-event forecasts produced by four UK institutions. Use of the robust test leads to the conclusion that certain forecasts are rational while use of the Gaussian-based test implies that certain forecasts are irrational. The difference in the results is due to the nature of the underlying data. Copyright © 2001 John Wiley & Sons, Ltd.

An empirical investigation of the effects of rounding on the SPF probabilities of decine and output growth histograms

I consider the possibility that respondents to the Survey of Professional Forecasters round their probability forecasts of the event that real output will decline in the future, as well as their reported output growth probability distributions. I make various plausible assumptions about respondents’ rounding practices, and show how these impinge upon the apparent mismatch between probability forecasts of a decline in output and the probabilities of this event implied by the annual output growth histograms. I find that rounding accounts for about a quarter of the inconsistent pairs of forecasts.

Temperature-dependent reduction pathways of complexes fac-[Re(CO)3(N-R-imidazole)(1,10-phenanthroline)]+ (R = H, CH3)

Peculiar reduction pathways of the complexes fac-[Re(imH)(CO)3(phen)]+ and fac-[Re(imCH3)(CO)3(phen)]+ (imH = imidazole, imCH3 = N-methylimidazole and phen = 1,10-phenanthroline) have been unravelled by performing combined cyclic voltammetric and in situ IR spectroelectrochemical experiments. In the temperature range of 293–233 K, the initial reduction of the phen ligand in [Re(imH)(CO)3(phen)]+ results in irreversible conversion of the imidazole ligand to 3-imidazolate by a rapid phen•−→ imH intramolecular electron transfer coupled with N H bond cleavage. This process is followed by second phen-localized 1e− reduction producing [ReI(3-im−)(CO)3(phen•−)]−, similar to the analogous 2,2'-bipyridine complex. In contrast to the bpy analogue, the stability of the phen•−-containing complexes is significantly affected by lowering the temperature. At 233 K, a secondary reaction occurs in both [Re(3-im−)(CO)3(phen•−)]− and [Re(imCH3)(CO)3(phen•−)]. The resulting products exhibit v(CO) wavenumbers indistinguishable from those of the parent phen•− complexes; however, their oxidation occurs at a considerably more positive electrode potential. It is proposed that these species are produced by a new C C bond formation between the C(2) site of 3-im− or imCH3 and the C(2) site of the phen•−ligand.

Synthesis and Electronic Structure of Dissymmetrical, Naphthalene-Bridged Sandwich Complexes [Cp′Fe(μ‑C10H8)MCp*]x (x = 0, +1; M =Fe, Ru; Cp′ = η5‑C5H2‑1,2,4‑tBu3; Cp* = η5‑C5Me5)

The dissymmetrical naphthalene-bridged complexes [Cp′Fe(μ-C10H8)FeCp*] (3; Cp* = η5-C5Me5, Cp′ = η5-C5H2-1,2,4-tBu3) and [Cp′Fe(μ-C10H8)RuCp*] (4) were synthesized via a one-pot procedure from FeCl2(thf)1.5, Cp′K, KC10H8, and [Cp* FeCl(tmeda)] (tmeda = N,N,N′,N′- tetramethylethylenediamine) or [Cp*RuCl]4, respectively. The symmetrically substituted iron ruthenium complex [Cp*Fe(μ-C10H8)RuCp*] (5) bearing two Cp* ligands was prepared as a reference compound. Compounds 3−5 are diamagnetic and display similar molecular structures, where the metal atoms are coordinated to opposite sides of the bridging naphthalene molecule. Cyclic voltammetry and UV/vis spectroelectrochemistry studies revealed that neutral 3−5 can be oxidized to monocations 3+−5+ and dications 32+−52+. The chemical oxidation of 3 and 4 with [Cp2Fe]PF6 afforded the paramagnetic hexafluorophosphate salts [Cp′Fe(μ-C10H8)FeCp*]PF6 ([3]PF6) and [Cp′Fe(μ-C10H8)RuCp*]PF6 ([4]PF6), which were characterized by various spectroscopic techniques, including EPR and 57Fe Mössbauer spectroscopy. The molecular structure of [4]PF6 was determined by X-ray crystallography. DFT calculations support the structural and spectroscopic data and determine the compositions of frontier molecular orbitals in the investigated complexes. The effects of substituting Cp* with Cp′ and Fe with Ru on the electronic structures and the structural and spectroscopic properties are analyzed.

Reconstruction of geomagnetic activity and near-Earth interplanetary conditions over the past 167 yr – Part 1: A new geomagnetic data composite

We present a new composite of geomagnetic activity which is designed to be as homogeneous in its construction as possible. This is done by only combining data that, by virtue of the locations of the source observatories used, have similar responses to solar wind and IMF (interplanetary magnetic field) variations. This will enable us (in Part 2, Lockwood et al., 2013a) to use the new index to reconstruct the interplanetary magnetic field, B, back to 1846 with a full analysis of errors. Allowance is made for the effects of secular change in the geomagnetic field. The composite uses interdiurnal variation data from Helsinki for 1845–1890 (inclusive) and 1893–1896 and from Eskdalemuir from 1911 to the present. The gaps are filled using data from the Potsdam (1891–1892 and 1897–1907) and the nearby Seddin observatories (1908–1910) and intercalibration achieved using the Potsdam–Seddin sequence. The new index is termed IDV(1d) because it employs many of the principles of the IDV index derived by Svalgaard and Cliver (2010), inspired by the u index of Bartels (1932); however, we revert to using one-day (1d) means, as employed by Bartels, because the use of near-midnight values in IDV introduces contamination by the substorm current wedge auroral electrojet, giving noise and a dependence on solar wind speed that varies with latitude. The composite is compared with independent, early data from European-sector stations, Greenwich, St Petersburg, Parc St Maur, and Ekaterinburg, as well as the composite u index, compiled from 2–6 stations by Bartels, and the IDV index of Svalgaard and Cliver. Agreement is found to be extremely good in all cases, except two. Firstly, the Greenwich data are shown to have gradually degraded in quality until new instrumentation was installed in 1915. Secondly, we infer that the Bartels u index is increasingly unreliable before about 1886 and overestimates the solar cycle amplitude between 1872 and 1883 and this is amplified in the proxy data used before 1872. This is therefore also true of the IDV index which makes direct use of the u index values.