Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons

Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min-hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function.

Crossbred cow adoption and milk market participation in a multivariate count data framework

Cross-bred cow adoption is an important and potent policy variable precipitating subsistence household entry into emerging milk markets. This paper focuses on the problem of designing policies that encourage and sustain milkmarket expansion among a sample of subsistence households in the Ethiopian highlands. In this context it is desirable to measure households’ ‘proximity’ to market in terms of the level of deficiency of essential inputs. This problem is compounded by four factors. One is the existence of cross-bred cow numbers (count data) as an important, endogenous decision by the household; second is the lack of a multivariate generalization of the Poisson regression model; third is the censored nature of the milk sales data (sales from non-participating households are, essentially, censored at zero); and fourth is an important simultaneity that exists between the decision to adopt a cross-bred cow, the decision about how much milk to produce, the decision about how much milk to consume and the decision to market that milk which is produced but not consumed internally by the household. Routine application of Gibbs sampling and data augmentation overcome these problems in a relatively straightforward manner. We model the count data from two sites close to Addis Ababa in a latent, categorical-variable setting with known bin boundaries. The single-equation model is then extended to a multivariate system that accommodates the covariance between crossbred-cow adoption, milk-output, and milk-sales equations. The latent-variable procedure proves tractable in extension to the multivariate setting and provides important information for policy formation in emerging-market settings

Syntheses, crystal structures and properties of sterically congested heteroleptic complexes of group 10 metal ions with p-tolylsulfonyl dithiocarbimate and 1,2-bis (diphenylphosphino) ethane

Three novel heteroleptic complexes of the type cis- [ML(dppe)] [M = Ni(II), Pd(II), Pt(II); L = p-tolylsulfonyl dithiocarbimate; dppe = 1,2-bis(diphenylphosphino)ethane] have been prepared and characterized. X-ray crystallography revealed the close proximity of one of the ortho phenyl protons of the dppe ligand to the metal in the Ni(II) complex showing existence of the less common C-H center dot center dot center dot Ni anagostic interactions observed for the first time in the dithio-phosphine mixed-ligand systems. The platinum complex showed a strong photoluminescence emission near visible region in CH(2)Cl(2) solution.

Convergence accommodation trumps accommodative convergence

Purpose. This symposium contribution presents research that shows that disparity cues within a near stimulus drive not only vergence but also most of the accommodation. Be-cause blur is a weaker cue, accommodative convergence is therefore only of minor significance for most individuals. Methods. The Infant Vision Laboratory at the University of Reading uses a Power Ref II photorefractor to collect simultaneous accommodation and convergence data from participants fixating targets moving in depth. By manipulating target characteristics, we have been able to test how blur, disparity and proximal cues each contribute to driving responses. Results. Results from a series of studies over the past 12 years have contributed to a coherent body of evidence suggesting that disparity cues override blur and proximity cues in most individuals. Some strabismic patients do use blur as a more strongly weighted cue, and this strategy could contribute to their symptoms, clinical characteristics and response to treatment. Conclusion. Although convergence accommodation is extremely difficult to measure clinically, clinicians should be aware of its importance in binocular vision and strabismus. Although CA/C relationships typically seem more important than AC/A, bo th only partly explain the interplay between convergence and accommodation.

Rigorous bounds on the nonlinear saturation of instabilities to parallel shear flows

A novel method is presented for obtaining rigorous upper bounds on the finite-amplitude growth of instabilities to parallel shear flows on the beta-plane. The method relies on the existence of finite-amplitude Liapunov (normed) stability theorems, due to Arnol'd, which are nonlinear generalizations of the classical stability theorems of Rayleigh and Fjørtoft. Briefly, the idea is to use the finite-amplitude stability theorems to constrain the evolution of unstable flows in terms of their proximity to a stable flow. Two classes of general bounds are derived, and various examples are considered. It is also shown that, for a certain kind of forced-dissipative problem with dissipation proportional to vorticity, the finite-amplitude stability theorems (which were originally derived for inviscid, unforced flow) remain valid (though they are no longer strictly Liapunov); the saturation bounds therefore continue to hold under these conditions.

Integrated palaeoecology and archaeology: a powerful approach for understanding pre-Columbian Amazonia

The old paradigm that Amazonia's tropical ecosystems prevented cultural development beyond small-scale shifting agricultural economies, that had little environmental impact, no longer holds true for much of Amazonia. A diversity of archaeological evidence, including terra preta soils, raised fields, causeways, large habitation mounds, geometric earthworks, and megalithic monuments, all point to considerable cultural complexity and environmental impacts. However, uncertainty remains over the chronology of these cultures, their diet and economy, and the scale of environmental impact and land use associated with them. Here, we argue that a cross-disciplinary approach, closely coupling palaeoecology and archaeology, can potentially resolve these uncertainties. We show how, with careful site selection (pairing small and large lakes, close proximity to archaeological sites, transects of soil pits) and choice of techniques (e.g., pollen, phytoliths, starch grains, charcoal, stable isotopes), these two disciplines can be successfully integrated to provide a powerful tool for investigating the relationship between pre-Columbian cultures and their environment.

L3 syntactic transfer selectivity and typological determinacy: the typological primacy model

The present article addresses the following question: what variables condition syntactic transfer? Evidence is provided in support of the position that third language (L3) transfer is selective, whereby, at least under certain conditions, it is driven by the typological proximity of the target L3 measured against the other previously acquired linguistic systems (cf. Rothman and Cabrelli Amaro, 2007, 2010; Rothman, 2010; Montrul et al., 2011). To show this, we compare data in the domain of adjectival interpretation between successful first language (L1) Italian learners of English as a second language (L2) at the low to intermediate proficiency level of L3 Spanish, and successful L1 English learners of L2 Spanish at the same levels for L3 Brazilian Portuguese. The data show that, irrespective of the L1 or the L2, these L3 learners demonstrate target knowledge of subtle adjectival semantic nuances obtained via noun-raising, which English lacks and the other languages share. We maintain that such knowledge is transferred to the L3 from Italian (L1) and Spanish (L2) respectively in light of important differences between the L3 learners herein compared to what is known of the L2 Spanish performance of L1 English speakers at the same level of proficiency (see, for example, Judy et al., 2008; Rothman et al., 2010). While the present data are consistent with Flynn et al.’s (2004) Cumulative Enhancement Model, we discuss why a coupling of these data with evidence from other recent L3 studies suggests necessary modifications to this model, offering in its stead the Typological Primacy Model (TPM) for multilingual transfer.

On the typological economy of syntactic transfer: word order and relative clause high/low attachment preference in L3 Brazilian Portuguese

One central question in the formal linguistic study of adult multilingual morphosyntax (i.e., L3/Ln acquisition) involves determining the role(s) the L1 and/or the L2 play(s) at the L3 initial state (e.g., Bardel & Falk, Second Language Research 23: 459–484, 2007; Falk & Bardel, Second Language Research: forthcoming; Flynn et al., The International Journal of Multilingualism 8: 3–16, 2004; Rothman, Second Language Research: forthcoming; Rothman & Cabrelli, On the initial state of L3 (Ln) acquisition: Selective or absolute transfer?: 2007; Rothman & Cabrelli Amaro, Second Language Research 26: 219–289, 2010). The present article adds to this general program, testing Rothman's (Second Language Research: forthcoming) model for L3 initial state transfer, which when relevant in light of specific language pairings, maintains that typological proximity between the languages is the most deterministic variable determining the selection of syntactic transfer. Herein, I present empirical evidence from the later part of the beginning stages of L3 Brazilian Portuguese (BP) by native speakers of English and Spanish, who have attained an advanced level of proficiency in either English or Spanish as an L2. Examining the related domains of syntactic word order and relative clause attachment preference in L3 BP, the data clearly indicate that Spanish is transferred for both experimental groups irrespective of whether it was the L1 or L2. These results are expected by Rothman's (Second Language Research: forthcoming) model, but not necessarily predicted by other current hypotheses of multilingual syntactic transfer; the implications of this are discussed.

Comparison of pollinators and natural enemies: a meta-analysis of landscape and local effects on abundance and richness in crops

To manage agroecosystems for multiple ecosystem services, we need to know whether the management of one service has positive, negative, or no effects on other services. We do not yet have data on the interactions between pollination and pest-control services. However, we do have data on the distributions of pollinators and natural enemies in agroecosystems. Therefore, we compared these two groups of ecosystem service providers, to see if the management of farms and agricultural landscapes might have similar effects on the abundance and richness of both. In a meta-analysis, we compared 46 studies that sampled bees, predatory beetles, parasitic wasps, and spiders in fields, orchards, or vineyards of food crops. These studies used the proximity or proportion of non-crop or natural habitats in the landscapes surrounding these crops (a measure of landscape complexity), or the proximity or diversity of non-crop plants in the margins of these crops (a measure of local complexity), to explain the abundance or richness of these beneficial arthropods. Compositional complexity at both landscape and local scales had positive effects on both pollinators and natural enemies, but different effects on different taxa. Effects on bees and spiders were significantly positive, but effects on parasitoids and predatory beetles (mostly Carabidae and Staphylinidae) were inconclusive. Landscape complexity had significantly stronger effects on bees than it did on predatory beetles and significantly stronger effects in non-woody rather than in woody crops. Effects on richness were significantly stronger than effects on abundance, but possibly only for spiders. This abundance-richness difference might be caused by differences between generalists and specialists, or between arthropods that depend on non-crop habitats (ecotone species and dispersers) and those that do not (cultural species). We call this the ‘specialist-generalist’ or ‘cultural difference’ mechanism. If complexity has stronger effects on richness than abundance, it might have stronger effects on the stability than the magnitude of these arthropod-mediated ecosystem services. We conclude that some pollinators and natural enemies seem to have compatible responses to complexity, and it might be possible to manage agroecosystems for the benefit of both. However, too few studies have compared the two, and so we cannot yet conclude that there are no negative interactions between pollinators and natural enemies, and no trade-offs between pollination and pest-control services. Therefore, we suggest a framework for future research to bridge these gaps in our knowledge.

Grey waters bright with Neolithic argonauts? Maritime connections and the Mesolithic-Neolithic transition within the 'western seaways' of Britain, c. 5000-3500 BC.

Careful examination of the probable natural conditions for travel in the North Sea and Irish Sea during the late Mesolithic are here combined with the latest radiocarbon dates to present a new picture of the transition to the Neolithic in the British Isles. The islands of the west were already connected by Mesolithic traffic and did not all go Neolithic at the same time. The introduction of the Neolithic package neither depended on seaborne incomers nor on proximity to the continent. More interesting forces were probably operating on an already busy seaway.

Linguistic and cognitive motivations for the typological primacy model of third language (L3) transfer: considering the role of timing of acquisition and proficiency in the previous languages

This article elucidates the Typological Primacy Model (TPM; Rothman, 2010, 2011, 2013) for the initial stages of adult third language (L3) morphosyntactic transfer, addressing questions that stem from the model and its application. The TPM maintains that structural proximity between the L3 and the L1 and/or the L2 determines L3 transfer. In addition to demonstrating empirical support for the TPM, this article articulates a proposal for how the mind unconsciously determines typological (structural) proximity based on linguistic cues from the L3 input stream used by the parser early on to determine holistic transfer of one previous (the L1 or the L2) system. This articulated version of the TPM is motivated by argumentation appealing to cognitive and linguistic factors. Finally, in line with the general tenets of the TPM, I ponder if and why L3 transfer might obtain differently depending on the type of bilingual (e.g. early vs. late) and proficiency level of bilingualism involved in the L3 process.

The inverse domino effect: are economic reforms contagious?

This article examines whether a country's economic reforms are affected by reforms adopted by other countries. Our theoretical model predicts that reforms are more likely when factors of production are internationally mobile and reforms are pursued in other economies. Using the change in the Index of Economic Freedom as the measure of market-liberalizing reforms and panel data (144 countries, 1995–2006), we test our model. We find evidence of the spillover of reforms. Moreover, consistent with our model, international trade is not a vehicle for the diffusion of economic reforms; rather the most important mechanism is geographical or cultural proximity.

Change in convergence and accommodation after two weeks of eye exercises in typical young adults

Abstract: Introduction Although eye exercises appear to help heterophoria, convergence insufficiency and intermittent strabismus, true treatment effects can be confounded by placebo, practice and encouragement factors. This study assessed objective changes in vergence and accommodation responses in typical naïve young adults after two weeks of exercises compared to control conditions to assess the extent of treatment effects occur above other factors. Methods 156 asymptomatic young adults were randomly assigned to 6 exercise groups or 2 no-treatment groups. Treatment targeted i) accommodation, ii)vergence, iii) both, iv) convergence>accommodation, v)accommodation>convergence, or vi) a placebo. All were re-tested under identical conditions, except for the second control group who were additionally encouraged during testing. Objective accommodation and vergence were assessed to a range of targets moving in depth containing combinations of blur, disparity and proximity/looming cues. Results Response gain improved more for less naturalistic targets where more improvement was possible. Convergence exercises improved vergence for near across all targets (P=.035). Mean accommodation changed similarly,but non-significantly. No other treatment group differed significantly from the non-encouraged control group, while encouraging effort produced significantly increased vergence (P=.004) and accommodation (P=.005) gains in the other control group. Conclusions True treatment effects were small, only significantly better after vergence exercises to a non-accommodative target, and were rarely related to response they were designed to improve. Exercising accommodation without convergence made no difference to accommodation to cues containing detail. Additional effort improved objective responses the most, so should be controlled carefully in research, and considered when auditing treatment.

Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon

Agonists of protease-activated receptor 2 (PAR(2)) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR(2)-evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI-labelled neurons contained PAR(2) immunoreactivity, confirming the presence of receptors on colonic neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR(2) activation with a brief application (3 min) of PAR(2) agonists, SLIGRL-NH(2) and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL-NH(2) markedly suppressed delayed rectifier I(K) currents (55% at 10 min), but had no effect on the transient I(A) current or TTX-resistant Na(+) currents. In whole-cell current-clamp recordings, the sustained excitability evoked by PAR(2) activation was blocked by the PKC inhibitor, calphostin, and the ERK(1/2) inhibitor PD98059. Studies of ERK(1/2) phosphorylation using confocal microscopy demonstrated that SLIGRL-NH(2) increased levels of immunoreactive pERK(1/2) in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR(2) receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier I(K) currents. Both PKC and ERK(1/2) mediate the PAR(2)-induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.

Characterization and antimicrobial efficacy against E. coli of a helium/air plasma at atmospheric pressure created in a plastic package

A plasma source, sustained by the application of a floating high voltage (±15 kV) to parallel-plate electrodes at 50 Hz, has been achieved in a helium/air mixture at atmospheric pressure (P = 105 Pa) contained in a zip-locked plastic package placed in the electrode gap. Some of the physical and antimicrobial properties of this apparatus were established with a view to ascertain its performance as a prototype for the disinfection of fresh produce. The current–voltage (I–V) and charge–voltage (Q–V) characteristics of the system were measured as a function of gap distance d, in the range (3 × 103 ≤ Pd ≤ 1.0 × 104 Pa m). The electrical measurements showed this plasma source to exhibit the characteristic behaviour of a dielectric barrier discharge in the filamentary mode and its properties could be accurately interpreted by the two-capacitance in series model. The power consumed by the discharge and the reduced field strength were found to decrease quadratically from 12.0 W to 4.5 W and linearly from 140 Td to 50 Td, respectively, in the range studied. Emission spectra of the discharge were recorded on a relative intensity scale and the dominant spectral features could be assigned to strong vibrational bands in the 2+ and 1− systems of N2 and ${\rm N}_2^+$ , respectively, with other weak signatures from the NO and OH radicals and the N+, He and O atomic species. Absolute spectral intensities were also recorded and interpreted by comparison with the non-equilibrium synthetic spectra generated by the computer code SPECAIR. At an inter-electrode gap of 0.04 m, this comparison yielded typical values for the electron, vibrational and translational (gas) temperatures of (4980 ± 100) K, (2700 ± 200) K and (300 ± 100) K, respectively and an electron density of 1.0 × 1017 m−3. A Boltzmann plot also provided a value of (3200 ± 200 K) for the vibrational temperature. The antimicrobial efficacy was assessed by studying the resistance of both Escherichia coli K12 its isogenic mutants in soxR, soxS, oxyR, rpoS and dnaK selected to identify possible cellular responses and targets related with 5 min exposure to the active gas in proximity of, but not directly in, the path of the discharge filaments. Both the parent strain and mutants populations were significantly reduced by more than 1.5 log cycles in these conditions, showing the potential of the system. Post-treatment storage studies showed that some transcription regulators and specific genes related to oxidative stress play an important role in the E. coli repair mechanism and that plasma exposure affects specific cell regulator systems.