Getting to the root of neuronal signalling in plant-parasitic nematodes using RNA interference

A variety of genes expressed in preparasitic second-stage juveniles (J2) of plant-parasitic nematodes appear to be vulnerable to RNA interference (RNAi) in vitro by coupling double-stranded (ds)RNA soaking with the artificial stimulation of pharyngeal pumping. Also, there is mounting evidence that the in planta generation of nematode-specific double-stranded RNAs (dsRNAs) has real utility in the control of these pests. Although neuronally-expressed genes in Caenorhabditis elegans are commonly refractory to RNAi, we have discovered that neuronally-expressed genes in plant-parasitic nematodes are highly susceptible to RNAi and that silencing can be induced by simple soaking procedures without the need for pharyngeal stimulation. Since most front-line anthelmintics that are used for the control of nematode parasites of animals and humans act to disrupt neuromuscular coordination, we argue that intercellular signalling processes associated with neurons have much appeal as targets for transgenic plant-based control strategies for plant-parasitic nematodes. FMRFamide-like peptides (FLPs) are a large family of neuropeptides which are intimately associated with neuromuscular regulation, and our studies on flp gene function in plant-parasitic nematodes have revealed that their expression is central to coordinated locomotory activities. We propose that the high level of conservation in nervous systems across nematodes coupled with the RNAi-susceptibility of neuronally-expressed genes in plant-parasitic nematodes provides a valuable research tool which could be used to interrogate neuronal signalling processes in nematodes.

Influence of predominant patterns of coordination on the exploitation of interaction torques in a two-joint rhythmic arm movement

In this study we investigate the coordination between rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow joint-complex, while manipulating the intersegmental dynamics by means of a 2-degrees of freedom (df) robot arm. We hypothesized that constraints imposed by the structure of the neuromuscular-skeletal system would (1) result in predominant pattern(s) of coordination in the absence of interaction torques and (2) influence the capabilities of participants to exploit artificially induced interaction torques. Two experiments were conducted in which different conditions of interaction torques were applied on the SP-axis as a function of FE movements. These conditions promoted different patterns of coordination between the 2-df. Control trials conducted in the absence of interaction torques revealed that both the in-phase (supination synchronized with flexion) and the anti-phase (pronation synchronized with flexion) patterns were spontaneously established by participants. The predominance of these patterns of coordination is explained in terms of the mechanical action of bi-articular muscles acting at the elbow joint-complex, and in terms of the reflexes that link the activity of the muscles involved. Results obtained in the different conditions of interaction torques revealed that those neuromuscular-skeletal constraints either impede or favor the exploitation of intersegmental dynamics depending on the context. Interaction torques were indeed found to be exploited to a greater extent in conditions in which the profiles of interaction torques favored one of the two predominant patterns of coordination (i.e., in-phase or anti-phase) as opposed to other patterns of coordination (e.g., 90 degrees or 270 degrees). Those results are discussed in relation to recent studies reporting exploitation of interaction torques in the context of rhythmic movements.

The consequences of resistance training for movement control in older adults

Older adults who undertake resistance training are typically seeking to maintain or increase their muscular strength with the goal of preserving or improving their functional capabilities. The extent to which resistance training adaptations lead to improved performance on tasks of everyday living is not particularly well understood. Indeed, studies examining changes in functional task performance experienced by older adults following periods of resistance training have produced equivocal findings. A clear understanding of the principles governing the transfer of resistance training adaptations is therefore critical in seeking to optimize the prescription of training regimes that have as their aim the maintenance and improvement of functional movement capacities in older adults. The degenerative processes that occur in the aging motor system are likely to influence heavily any adaptations to resistance training and the subsequent transfer to functional task performance. The resulting characteristics of motor behavior, such as the substantial decline in the rate of force development and the decreased steadiness of force production, may entail that specialized resistance training strategies are necessary to maximize the benefits for older adults. In this review, we summarize the alterations in the neuromuscular system that are responsible for the declines in strength, power, and force control, and the subsequent deterioration in the everyday movement capabilities of older adults. We examine the literature concerning the neural adaptations that older adults experience in response to resistance training, and consider the readiness with which these adaptations will improve the functional movement capabilities of older adults.

Haptic information stabilizes and destabilizes coordination dynamics

Goal-directed, coordinated movements in humans emerge from a variety of constraints that range from 'high-level' cognitive strategies based oil perception of the task to 'low-level' neuromuscular-skeletal factors such as differential contributions to coordination from flexor and extensor muscles. There has been a tendency in the literature to dichotomize these sources of constraint, favouring one or the other rather than recognizing and understanding their mutual interplay. In this experiment, subjects were required to coordinate rhythmic flexion and extension movements with an auditory metronome, the rate of which was systematically increased. When subjects started in extension on the beat of the metronome, there was a small tendency to switch to flexion at higher rates, but not vice versa. When subjects: were asked to contact a physical stop, the location of which was either coincident with or counterphase to the auditor) stimulus, two effects occurred. When haptic contact was coincident with sound, coordination was stabilized for both flexion and extension. When haptic contact was counterphase to the metronome, coordination was actually destabilized, with transitions occurring from both extension to flexion on the beat and from flexion to extension on the beat. These results reveal the complementary nature of strategic and neuromuscular factors in sensorimotor coordination. They also suggest the presence of a multimodal neural integration process-which is parametrizable by rate and context - in which intentional movement, touch and sound are bound into a single, coherent unit.

Social exclusion and social capital: A comparison and critique

Social exclusion and social capital are widely used concepts with multiple and ambiguous definitions. Their meanings and indicators partially overlap, and thus they are sometimes used interchangeably to refer to the inter-relations of economy and society. Both ideas could benefit from further specification and differentiation. The causes of social exclusion and the consequences of social capital have received the fullest elaboration, to the relative neglect of the outcomes of social exclusion and the genesis of social capital. This article identifies the similarities and differences between social exclusion and social capital. We compare the intellectual histories and theoretical orientations of each term, their empirical manifestations and their place in public policy. The article then moves on to elucidate further each set of ideas. A central argument is that the conflation of these notions partly emerges from a shared theoretical tradition, but also from insufficient theorizing of the processes in which each phenomenon is implicated. A number of suggestions are made for sharpening their explanatory focus, in particular better differentiating between cause and consequence, contextualizing social relations and social networks, and subjecting the policy 'solutions' that follow from each perspective to critical scrutiny. Placing the two in dialogue is beneficial for the further development of each.

The Hindered Self-Help: Housing Policies, Politics And Poverty In Kolkata, India

The housing dimension in Kolkata has been changing in recent years. Since 1991, the city has initiated housing reform that has taken many forms and manifestations characterized by the reduction in social allocation, cutbacks in public funding and promotion of a real estate culture in close partnership between the state and private actors. There has been increasing concern about the housing condition of the poor in the deserted slums and bustee settlements amidst the evident ‘poor blindness’ in housing and investment policies. Against this background the paper discusses self-help housing in Kolkata. It seeks to answer a simple question – why the concept of self-help has not been recognised as a viable policy option for a city with widespread slums and bustee settlements by visiting the complex urban context of Kolkata set within the city's politics, poverty and policies. The paper concludes that there is a need to recognise the existing structural duality in the city and support self-help housing as a parallel housing approach.

A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartcareTM/PS

Objective
Preliminary assessment of an automated weaning system (SmartCare™/PS) compared to usual management of weaning from mechanical ventilation performed in the absence of formal protocols.


Design and setting
A randomised, controlled pilot study in one Australian intensive care unit.


Patients
A total of 102 patients were equally divided between SmartCare/PS and Control.

Interventions
The automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success (“separation potential”).

Measurements and results
The median time from the first identified point of suitability for weaning commencement to the state of “separation potential” using SmartCare/PS was 20 h (interquartile range, IQR, 2–40) compared to 8 h (IQR 2–43) with Control (log-rank P = 0.3). The median time to successful extubation was 43 h (IQR 6–169) using SmartCare/PS and 40 (14–87) with Control (log-rank P = 0.6). Unadjusted, the estimated probability of reaching “separation potential” was 21% lower (95% CI, 48% lower to 20% greater) with SmartCare/PS compared to Control. Adjusted for other covariates (age, gender, APACHE II, SOFAmax, neuromuscular blockade, corticosteroids, coma and elevated blood glucose), these estimates were 31% lower (95% CI, 56% lower to 9% greater) with SmartCare/PS. The study groups showed comparable rates of reintubation, non-invasive ventilation post-extubation, tracheostomy, sedation, neuromuscular blockade and use of corticosteroids.

Conclusions
Substantial reductions in weaning duration previously demonstrated were not confirmed when the SmartCare/PS system was compared to weaning managed by experienced critical care specialty nurses, using a 1:1 nurse-to-patient ratio. The effect of SmartCare/PS may be influenced by the local clinical organisational context.

'Last Vegas?'

This article, and the research out of which it springs, has a number of points of origin; it may also have more than one point of conclusion even as it argues that the current manifestation of Las Vegas could well be read as its last. This is not to say that Las Vegas will cease to create its new versions of itself; after all, this is one of the main sustaining factors of Las Vegas’ success in the last two decades as a new Strip on Las Vegas Boulevard has arisen from the demolitions and redesigns of the original Las Vegas Strip of the 1950s and 1960s. What is argued for here is a reading of Vegas as a terminal point within American culture and particularly within its visual realms. Las Vegas’ place within the dynamics of American visual and exhibition culture comes as the latest in a sequence which, since the nineteenth century, has included among its manifestations World’s Fairs, side shows, freak shows and travelling carnivals. America’s experiments in the visual domain have been updated in both the twentieth- and twenty-first centuries in a variety of spectacular forms and entertainment zones (Disneyland, EPCOT, the new Las Vegas). Vegas is the ultimate incarnation of a carnivalised display culture, the city’s casino Strip reclothed primarily as a theme park for digital camera-toting tourists than as a resort for dedicated gamblers. The possibility that the current incarnation of Las Vegas of late 2009 and 2010 will be the last Vegas hovers as a spectral remnant of the economic downturn and financial collapse of 2008, marked by the unfinished skeletons of projected new casino hotels on Las Vegas Boulevard and by a sudden reversal of fortune for the nation’s favourite gaming location.

Maternal imagination: Reconceiving first impressions

The concept of maternal imagination, whereby the disordered thoughts and impressions of pregnant women are used to explain the prevalence of monstrous births, was at its height during the early modern period, albeit it with many prior and subsequent manifestations. Against a more familiar, and enduring, medieval and Renaissance context of supernatural agency at work, the device of MI was seen as a 'naturalistic' model more in keeping with the advent of Enlightenment scientism. Nonetheless, the debate around it was ferocious and indicative more of a masculine anxiety about female desire and generative power than of a concern for impartial explanation. In problematizing a simply descriptive approach to archival material, my purpose is to explore what is at stake in the competing discourses that seem alternately, and even simultaneously, to empower and degrade the place of the mother. What is the unspoken of an historical debate that prefigures our contemporary interest in feminine excess?

FMRFamide-like peptides (FLPs) enhance voltage-gated calcium currents to elicit muscle contraction in the human parasite Schistosoma mansoni.

Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway.

Identifying early signs of aggression: psychometric properties of the cardiff infant contentiousness scale

Our aim was to develop an age-appropriate measure of early manifestations of aggression. We constructed a questionnaire about normative developmental milestones into which a set of items measuring infants’ use of physical force against people and expressed anger were included. These items comprise the Cardiff Infant Contentiousness Scale (CICS). Evidence for the reliability and validity of the CICS is provided from analyses of a sample of N5310 British infants, assessed at a mean age of 6 months as part of a larger longitudinal study of the development of aggression. The informants’ CICS ratings demonstrated reasonable levels of internal consistency and interrater agreement. Informants’ ratings were validated by observations of infants’ distress in response to restraint in a car seat. Longitudinal analyses revealed that contentiousness was stable over time and that contentiousness at 6 months predicted infants’ later use of force with peers. When used in the company of other methods, the simple four-item CICS scale could serve as a useful screen for early manifestations of aggressiveness in human infants.

Arteriolar involvement in the microvascular lesions of diabetic retinopathy: Implications for pathogenesis

Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term aminal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease.

Massive stars exploding in a He-rich circumstellar medium - III. SN 2006jc: infrared echoes from new and old dust in the progenitor CSM

We present near- (NIR) and mid-infrared (MIR) photometric data of the Type Ibn supernova (SN) 2006jc obtained with the United Kingdom Infrared Telescope (UKIRT), the Gemini North Telescope and the Spitzer Space Telescope between days 86 and 493 post-explosion. We find that the IR behaviour of SN 2006jc can be explained as a combination of IR echoes from two manifestations of circumstellar material. The bulk of the NIR emission arises from an IR echo from newly condensed dust in a cool dense shell (CDs) produced by the interaction of the ejecta Outward shock with a dense shell of circumstellar material ejected by the progenitor in a luminous blue variable (LBV)-like outburst about two years prior to the SN explosion. The CDs dust mass reaches a modest 3.0 x 10(-4) M-circle dot by day 230. While dust condensation within a CDs formed behind the ejecta inward shock has been proposed before for one event (SN 1998S), SN 2006jc is the first one showing evidence for dust condensation in a CDs formed behind the ejecta outward shock in the circumstellar material. At later epochs, a substantial and growing contribution to the IR fluxes arises from an IR echo from pre-existing dust in the progenitor wind. The mass of the pre-existing circumstellar medium (CSM) dust is at least similar to 8 x 10(-3) M-circle dot. This paper therefore adds to the evidence that mass-loss from the progenitors of core-collapse SNe could be a major source of dust in the Universe. However, yet again, we see no direct evidence that the explosion of an SN produces anything other than a very modest amount of dust.

Religion, Human Rights, Equality and the Public Sphere

This article distinguishes three different conceptions of the relationship between religion and the public sphere. The reconciliation of these different aspects of freedom of religion can be seen to give rise to considerable difficulties in practice, and the legal and political systems of several Western European countries are struggling to cope. Four recurring issues that arise in this context are identified and considered: what is a 'religion' and what are 'religious' beliefs and practices for the purposes of the protection of 'freedom of religion', together with the closely related issue of who decides these questions; what justification there is for a provision guaranteeing freedom of religion at all; which manifestations of religious association are so unacceptable as to take the association outside the protection of freedom of religion altogether; and what weight should be given to freedom of religion when this freedom stands opposed to other values. It is argued that the scope and meaning of human rights in this context is anything but settled and that this gives an opportunity to those who support a role for religion in public life to intervene.