Role for protease activity in visceral pain in irritable bowel syndrome

Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-kappaB. In addition, increased proteolytic activity was measured in vivo, in colonic washes from IBS compared with control patients. Trypsin and tryptase expression and release were increased in colonic biopsies from IBS patients compared with control subjects. Biopsies from IBS patients (but not controls) released mediators that sensitized murine sensory neurons in culture. Sensitization was prevented by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR2). Supernatants from colonic biopsies of IBS patients, but not controls, also caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon. These pronociceptive effects were inhibited by serine protease inhibitors and a PAR2 antagonist and were absent in PAR2-deficient mice. Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR2.

Knowledge of A/A'-dependencies on subject extraction with two types of infinitives in non-native Portuguese adult bilingualism

Within generative L2 acquisition research there is a longstanding debate as to what underlies observable differences in L1/L2 knowledge/ performance. On the one hand, Full Accessibility approaches maintain that target L2 syntactic representations (new functional categories and features) are acquirable (e.g., Schwartz & Sprouse, 1996). Conversely, Partial Accessibility approaches claim that L2 variability and/or optionality, even at advanced levels, obtains as a result of inevitable deficits in L2 narrow syntax and is conditioned upon a maturational failure in adulthood to acquire (some) new functional features (e.g., Beck, 1998; Hawkins & Chan, 1997; Hawkins & Hattori, 2006; Tsimpli & Dimitrakopoulou, 2007). The present study tests the predictions of these two sets of approaches with advanced English learners of L2 Brazilian Portuguese (n = 21) in the domain of inflected infinitives. These advanced L2 learners reliably differentiate syntactically between finite verbs, uninflected and inflected infinitives, which, as argued, only supports Full Accessibility approaches. Moreover, we will discuss how testing the domain of inflected infinitives is especially interesting in light of recent proposals that Brazilian Portuguese colloquial dialects no longer actively instantiate them (Lightfoot, 1991; Pires, 2002, 2006; Pires & Rothman, 2009; Rothman, 2007).

Input type and parameter resetting: is naturalistic input necessary?

It has been argued that extended exposure to naturalistic input provides L2 learners with more of an opportunity to converge of target morphosyntactic competence as compared to classroom-only environments, given that the former provide more positive evidence of less salient linguistic properties than the latter (e.g., Isabelli 2004). Implicitly, the claim is that such exposure is needed to fully reset parameters. However, such a position conflicts with the notion of parameterization (cf. Rothman and Iverson 2007). In light of two types of competing generative theories of adult L2 acquisition – the No Impairment Hypothesis (e.g., Duffield and White 1999) and so-called Failed Features approaches (e.g., Beck 1998; Franceschina 2001; Hawkins and Chan 1997), we investigate the verifiability of such a claim. Thirty intermediate L2 Spanish learners were tested in regards to properties of the Null-Subject Parameter before and after study-abroad. The data suggest that (i) parameter resetting is possible and (ii) exposure to naturalistic input is not privileged.

An oceanic origin for the increase of atmospheric radiocarbon during the Younger Dryas

Variations in carbon-14 to carbon-12 ratio in the atmosphere (Δ14Catm) provide a powerful diagnostic for elucidating the timing and nature of geophysical and anthropological change. The (Atlantic) marine archive suggests a rapid Δ14Catm increase of 50‰ at the onset of the Younger Dryas (YD) cold reversal (12.9–11.7 kyr BP), which has not yet been satisfactorily explained in terms of magnitude or causal mechanism, as either a change in ocean ventilation or production rate. Using Earth-system model simulations and comparison of marine-based radiocarbon records from different ocean basins, we demonstrate that the YD Δ14Catm increase is smaller than suggested by the marine archive. This is due to changes in reservoir age, predominantly caused by reduced ocean ventilation.

Towards radiocarbon calibration beyond 28ka using speleothems from the Bahamas

We present a new speleothem record of atmospheric Δ14C between 28 and 44 ka that offers considerable promise for resolving some of the uncertainty associated with existing radiocarbon calibration curves for this time period. The record is based on a comprehensive suite of AMS 14C ages, using new low-blank protocols, and U–Th ages using high precision MC-ICPMS procedures. Atmospheric Δ14C was calculated by correcting 14C ages with a constant dead carbon fraction (DCF) of 22.7 ± 5.9%, based on a comparison of stalagmite 14C ages with the IntCal04 (Reimer et al., 2004) calibration curve between 15 and 11 ka. The new Δ14C speleothem record shows similar structure and amplitude to that derived from Cariaco Basin foraminifera (Hughen et al., 2004, 2006), and the match is further improved if the latter is tied to the most recent Greenland ice core chronology (Svensson et al., 2008). These data are however in conflict with a previously published 14C data set for a stalagmite record from the Bahamas — GB-89-24-1 (Beck et al., 2001), which likely suffered from 14C analytical blank subtraction issues in the older part of the record. The new Bahamas speleothem ∆14C data do not show the extreme shifts between 44 and 40 ka reported in the previous study (Beck et al., 2001). Causes for the observed structure in derived atmospheric Δ14C variation based on the new speleothem data are investigated with a suite of simulations using an earth system model of intermediate complexity. Data-model comparison indicates that major fluctuations in atmospheric ∆14C during marine isotope stage 3 is primarily a function of changes in geomagnetic field intensity, although ocean–atmosphere system reorganisation also played a supporting role.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Planning at the neighbourhood scale: localism, dialogic politics and the modulation of community action

This paper builds upon literature examining the foreclosing of community interventions to show how a resident-led anti-road-noise campaign in South-Eastern England has been framed, managed and modulated by authorities. We situate the case within wider debates considering dialogical politics. For advocates, this offers the potential for empowerment through non-traditional forums (Beck, 1994; Giddens, 1994). Others view such trends, most recently expressed as part of the localism agenda, with suspicion (Haughton et al, 2013; Mouffe, 2005). The paper brings together these literatures to analyse the points at which modulation occurs in the community planning process. We describe the types of counter-tactics residents deployed to deflect the modulation of their demands, and the events that led to the outcome. We find that community planning offers a space - albeit one that is tightly circumscribed - within which (select) groups can effect change. The paper argues that the detail of neighbourhood-scale actions warrant further attention, especially as governmental enthusiasm for dialogical modes of politics shows no sign of abating.

State-resolved gas-surface reactivity of methane in the symmetric C-H stretch vibration on Ni(100)

The state-resolved reactivity of CH4 in its totally symmetric C-H stretch vibration (�1) has been measured on a Ni(100) surface. Methane molecules were accelerated to kinetic energies of 49 and 63:5 kJ=mol in a molecular beam and vibrationally excited to �1 by stimulated Raman pumping before surface impact at normal incidence. The reactivity of the symmetric-stretch excited CH4 is about an order of magnitude higher than that of methane excited to the antisymmetric stretch (�3) reported by Juurlink et al. [Phys. Rev. Lett. 83, 868 (1999)] and is similar to that we have previously observed for the excitation of the first overtone (2�3). The difference between the state-resolved reactivity for �1 and �3 is consistent with predictions of a vibrationally adiabatic model of the methane reaction dynamics and indicates that statistical models cannot correctly describe the chemisorption of CH4 on nickel.

Mode-specific reactivity of CH4 on Pt(110)-(1Ã2): The concerted role of stretch and bend excitation

The state-resolved reaction probability of CH4 on Pt�110-�1�2 was measured as a function of CH4 translational energy for four vibrational eigenstates comprising different amounts of C-H stretch and bend excitation. Mode-specific reactivity is observed both between states from different polyads and between isoenergetic states belonging to the same polyad of CH4. For the stretch/bend combination states, the vibrational efficacy of reaction activation is observed to be higher than for either pure C-H stretching or pure bending states, demonstrating a concerted role of stretch and bend excitation in C-H bond scission. This concerted role, reflected by the nonadditivity of the vibrational efficacies, is consistent with transition state structures found by ab initio calculations and indicates that current dynamical models of CH4 chemisorption neglect an important degree of freedom by including only C-H stretching motion.

How Pragmatically Odd! Interface Delays and Pronominal Subject Distribution in the L2 Spanish of English Natives

Sorace (2000, 2005) has claimed that while L2 learners can easily acquire properties of L2 narrow syntax they have significant difficulty with regard to interpretation and the discourse distribution of related properties, resulting in so-called residual optionality. However, there is no consensus as to what this difficulty indicates. Is it related to an insurmountable grammatical representational deficit (in the sense of representation deficit approaches; e.g. Beck 1998, Franceschina 2001, Hawkins 2005), is it due to cross-linguistic interference, or is it just a delay due to a greater complexity involved in the acquisition of interface-conditioned properties? In this article, I explore the L2 distribution of null and overt subject pronouns of English speaking learners of L2 Spanish. While intermediate learners clearly have knowledge of the syntax of Spanish null subjects, they do not have target-like pragmatic knowledge of their distribution with overt subjects. The present data demonstrate, however, that this difficulty is overcome at highly advanced stages of L2 development, thus suggesting that properties at the syntax-pragmatics interface are not destined for inevitable fossilization.

Assessment of the CMD Mini-Explorer, a new low-frequency multi-coil electromagnetic device, for archaeological investigations

In this article we assess the abilities of a new electromagnetic (EM) system, the CMD Mini-Explorer, for prospecting of archaeological features in Ireland and the UK. The Mini-Explorer is an EM probe which is primarily aimed at the environmental/geological prospecting market for the detection of pipes and geology. It has long been evident from the use of other EM devices that such an instrument might be suitable for shallow soil studies and applicable for archaeological prospecting. Of particular interest for the archaeological surveyor is the fact that the Mini-Explorer simultaneously obtains both quadrature (‘conductivity’) and in-phase (relative to ‘magnetic susceptibility’) data from three depth levels. As the maximum depth range is probably about 1.5 m, a comprehensive analysis of the subsoil within that range is possible. As with all EM devices the measurements require no contact with the ground, thereby negating the problem of high contact resistance that often besets earth resistance data during dry spells. The use of the CMD Mini-Explorer at a number of sites has demonstrated that it has the potential to detect a range of archaeological features and produces high-quality data that are comparable in quality to those obtained from standard earth resistance and magnetometer techniques. In theory the ability to measure two phenomena at three depths suggests that this type of instrument could reduce the number of poor outcomes that are the result of single measurement surveys. The high success rate reported here in the identification of buried archaeology using a multi-depth device that responds to the two most commonly mapped geophysical phenomena has implications for evaluation style surveys. Copyright © 2013 John Wiley & Sons, Ltd.