A timing-specific memory distortion effect in young children

It has been suggested that there are systematic distortions in children's memory for temporal durations, such that children's memory is not just less accurate than that of adults but qualitatively different. Experiment I replicated the memory distortion effect by demonstrating developmental change in the tendency to confuse a reference duration with one that is shorter rather than longer than it. When the long-term memory demands of the task were reduced by providing reminders of the reference duration on every trial, there were no such qualitative changes in error patterns (Experiment 2). Further evidence for developmental changes in memory distortion was found in the temporal generalization task of Experiment 3, in which stimuli were spaced logarithmically rather than linearly. In Experiment 4, a similar distortion pattern was absent in a task in which children made judgments about the pitch rather than the duration of stimuli, suggesting the effect may be specific to time estimation. (C) 2003 Elsevier Inc. All rights reserved.

Relations between premise similarity and inductive strength

According to the diversity principle, diverse evidence is strong evidence. There has been considerable evidence that people respect this principle in inductive reasoning. However, exceptions may be particularly informative. Medin, Coley, Storms, and Hayes (2003) introduced a relevance theory of inductive reasoning and used this theory to predict exceptions, including the nondiversity-by-property-reinforcement effect. A new experiment in which this phenomenon was investigated is reported here. Subjects made inductive strength judgments and similarity judgments for stimuli from Medin et al. (2003). The inductive strength judgments showed the same pattern as that in Medin et al. (2003); however, the similarity judgments suggested that the pattern should be interpreted as a diversity effect, rather than as a nondiversity effect. It is concluded that the evidence regarding the predicted nondiversity-by-property-reinforcement effect does not give distinctive support for relevance theory, although this theory does address other results.

Type XVIII collagen degradation products in acute lung injury

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge.

Appearance of the frequency-doubling stimulus at threshold.

PURPOSE. It has been argued that the threshold for detecting frequency-doubling (FD) technology perimeter stimuli differs from the threshold for perceiving spatial structure (pattern) in the same targets. Thresholds for perceiving spatial structure have typically been assessed using orientation-identification experiments. The authors investigated the influence of orientation, edge profile, and psychophysical method on the origin of the reported differences in detection and orientation-identification thresholds for FD gratings.

METHODS. Detection and orientation-identification thresholds were determined in 12 observers with the use of FD stimuli (0.25 cyc/deg, 25 Hz) presented centrally and at 15° eccentricity. Edge profile (square- and Gaussian-windowed) and orientation (horizontal, vertical, and oblique) were independently modified. Detection thresholds were also measured for spatially uniform flickering targets (25 Hz). Orientation-identification thresholds using a two-alternative forced choice (2-AFC) and a two-interval forced choice (2-IFC) method were also compared in five experienced observers.

RESULTS. Orientation-identification and detection thresholds did not significantly differ under any condition tested. Orientation-identification thresholds obtained with 2-AFC were not significantly different from those obtained with 2-IFC. Thresholds for spatially uniform flicker were significantly lower than for FD stimuli.

CONCLUSIONS. The authors found that orientation-identification and detection thresholds for FD gratings did not differ and argue that recent findings to the contrary arise from the inappropriate use of spatially uniform flicker targets as alternatives in 2-IFC experiments.

Triggered drug delivery from biomaterials

Importance of the field: Conventional dosing methods are frequently unable to deliver the clinical requirement of the patient. The ability to control the delivery of drugs from implanted materials is difficult to achieve, but offers promise in diverse areas such as infection-resistant medical devices and 10 responsive implants for diabetics. Areas covered in this review: This review gives a broad overview of recent progress in the use of triggers that can be used to achieve modulation of drug release rates from implantable biomaterials. In particular, these can be classified as being responsive to one or more of the following stimuli: a 15 chemical species, light, heat, magnetism, ultrasound and mechanical force. What the reader will gain: An overview of the potential for triggered drug delivery to give methods for tailoring the dose, location and time of release of a wide range of drugs where traditional dosing methods are not suitable. Particular emphasis is given to recently reported systems, and important 20 historical reports are included. Take home message: The use of externally or internally applied triggers of drug delivery to biomaterials has significant potential for improved delivery modalities and infection resistance.

Gender differences, responsiveness and memory of a potentially painful event in hermit crabs

Nonreflexive responses to a noxious event and prolonged memory are key criteria of a pain experience. In a previous study, hermit crabs, Pagurus bernhardus, that received a small electric shock within their shell often temporarily evacuated the shell and some groomed their abdomen and/or moved away from their vital resource. Most, however, returned to the shell. When offered a new shell 20 s later, shocked crabs were more likely than nonshocked crabs to approach and move into a new shell and did so more quickly (Elwood & Appel 2009, Animal Behaviour, 77, 1243-1246). Here we examined how increasing the time between the shock and the offering of a new shell influences the response. There was evidence of a memory of the aversive shock that lasted at least 1 day. Crabs tested after 30 min and 1 day were more likely to approach the shell and new shells were more likely to be taken 30 min after the shock. Shocked crabs approached the new shell more quickly and used fewer probes of the chelipeds prior to moving in and these results were stable over time and significant for specific times up to 1 day. Females were more likely than males to evacuate shells and did so after fewer shocks. These results extend previous work and demonstrate an extended memory of having been shocked. The findings are consistent with respect to criteria for pain that are accepted for vertebrates.

Motivational trade-offs and potential pain experience in hermit crabs

One criterion of pain experience is that the emotional response to pain may be traded-off against other motivational requirements. This was tested in hermit crabs, housed in either preferred or unpreferred species of shells, by subjecting their abdomens to electric shocks of gradually increasing intensity. The first observable response was not affected by shell species but those in preferred shells evacuated at a higher shock level than those in poor quality shells. Thus, they seem to trade-off the requirement to retain a high quality shell with that of avoidance of the noxious stimulus. Some crabs returned to their shells and those that got back into the preferred species did so with less probing of the aperture before getting in and subsequently thrust their abdomen in and out less often in further investigation, thus confirming their shell species preference. Not all crabs returned to the vicinity of the shell and some attempted to climb the wall of the experimental chamber. Others engaged in shell rapping as if in a fight and grooming of the abdomen was noted. These findings are consistent with the idea of a pain experience rather than a nociceptive reflex. (C) 2009 Elsevier B.V. All rights reserved.

Pain experience in hermit crabs?

Pain may be inferred when the responses to a noxious stimulus are not reflexive but are traded off against other motivational requirements, the experience is remembered and the situation is avoided in the future. To investigate whether decapods feel pain we gave hermit crabs, Pagurus bernhardus, small electric shocks within their shells. Only crabs given shocks evacuated their shells indicating the aversive nature of the stimulus, but fewer crabs evacuated from a preferred species of shell indicating a motivational trade-off. Some crabs that evacuated attacked the shell in the manner seen in a shell fight. Most crabs, however, did not evacuate at the stimulus level we used, but when these were subsequently offered a new shell, shocked crabs were more likely to approach and enter the new shell. Furthermore, they approached that shell more quickly, investigated it for a shorter time and used fewer cheliped probes within the aperture prior to moving in. Thus the experience of the shock altered future behaviour in a manner consistent with a marked shift in motivation to get a new shell to replace the one occupied. The results are consistent with the idea of pain in these animals. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

Background: Glycogen synthase kinase-3 (GSK-8) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.

DNA methylation profiling in cell models of diabetic nephropathy

We have previously identified differentially expressed genes in cell models of diabetic nephropathy and renal biopsies. Here we have performed quantitative DNA methylation profiling in cell models of diabetic nephropathy. Over 3,000 CpG units in the promoter regions of 192 candidate genes were assessed in unstimulated human mesangial cells (HMCs) and proximal tubular epithelial cells (PTCs) compared to HMCs or PTCs exposed to appropriate stimuli. A total of 301 CpG units across 38 genes (similar to 20%) were identified as differentially methylated in unstimulated HMCs versus PTCs. Analysis of amplicon methylation values in unstimulated versus stimulated cell models failed to demonstrate a >20% difference between amplicons. In conclusion, our results demonstrate that specific DNA methylation signatures are present in HMCs and PTCs, and standard protocols for exposure of renal cells to stimuli that alter gene expression may be insufficient to replicate possible alterations in DNA methylation profiles in diabetic nephropathy.

Intermedin (Adrenomedullin-2) a novel counter-regulatory peptide in the cardiovascular and renal systems

Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (AM). Proteolytic processing of a larger precursor yields a series of biologically active C-terminal fragments, IMD1–53, IMD1–47 and IMD8–47. IMD shares a family of receptors with AM and CGRP composed of a calcitonin-receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins (RAMP). Compared to CGRP, IMD is less potent at CGRP1 receptors but more potent at AM1 receptors and AM2 receptors; compared to AM, IMD is more potent at CGRP1 receptors but less potent at AM1 and AM2 receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water-electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia-reperfusion injury and exerts an anti-growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter-regulatory peptide in the heart.

Social categorizations, social comparisons and stigma: Presentations of self in people with learning difficulties

Self-categorization theory stresses the importance of the context in which the metacontrast principle is proposed to operate. This study is concerned with how 'the pool of psychologically relevant stimuli' (Turner, Hogg, Oakes, Reicher & Wetherell, 1987, p. 47) comprising the context is determined. Data from interviews with 33 people with learning difficulties were used to show how a positive sense of self might be constructed by members of a stigmatized social category through the social worlds that they describe, and therefore the social comparisons and categorizations that are made possible. Participants made downward comparisons which focused on people with learning difficulties who were less able or who displayed challenging behaviour, and with people who did not have learning difficulties but who, according to the participants, behaved badly, such as beggars, drunks and thieves. By selection of dimensions and comparison others, a positive sense of self and a particular set of social categorizations were presented. It is suggested that when using self-categorization theory to study real-world social categories, more attention needs to be paid to the involvement of the perceiver in determining which stimuli are psychologically relevant since this is a crucial determinant of category salience.

A comparison of monkey and human motion processing mechanisms

Single-cell recording studies have provided vision scientists with a detailed understanding of motion processing at the neuronal level in non-human primates. However, despite the development of brain imaging techniques, it is not known to what extent the response characteristics of motion-sensitive neurons in monkey brain mirror those of human motion sensitive neurons. Using a motion adaptation paradigm, the direction aftereffect, we recently provided evidence of a strong resemblance in the response functions of motion-sensitive neurons in monkey and human to moving dot patterns differing in dot density. Here we describe a series of experiments in which measurements of the direction aftereffect are used to infer the response characteristics of human motion-sensitive neurons when viewing transparent motion and moving patterns that differ in their signal-to-noise ratio (motion coherence). In the case of transparent motion stimuli, our data suggest suppressed activity of motion-sensitive neurons similar to that reported for macaque monkey. In the case of motion coherence, our results are indicative of a linear relationship between signal intensity (coherence) and neural activity; a pattern of activity which also bears a striking similarity to macaque neural activity. These findings strongly suggest that monkey and human motionsensitive neurons exhibit similar response and inhibitory characteristics.

Thrombopoietin, flt3-ligand and c-kit-ligand modulate HOX gene expression in expanding cord blood CD133(+) cells

Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic and intrinsic stimuli. Extrinsic modulators include growth factors and cell adhesion molecules, whereas intrinsic regulation is achieved with many transcription factor families, of which the HOX gene products are known to be important in haemopoiesis. Umbilical cord blood CD133(+) HSPC proliferation potential was tested in liquid culture with 'TPOFLK' (thrombopoietin, flt-3 ligand and c-kit ligand, promoting HSPC survival and self-renewal), in comparison to 'K36EG' (c-kit-ligand, interleukins-3 and -6, erythropoietin and granulocyte colony-stimulating factor, inducing haemopoietic differentiation). TPOFLK induced a higher CD133(+) HSPC proliferation (up to 60-fold more, at week 8) and maintained a higher frequency of the primitive colony-forming cells than K36EG. Quantitative polymerase chain reaction analysis revealed opposite expression patterns for specific HOX genes in expanding cord blood CD133(+) HSPC. After 8 weeks in liquid culture, TPOFLK increased the expression of HOX B3, B4 and A9 (associated with uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in committed myeloid cells) when compared to K36EG. These results suggest that TPOFLK induces CD133(+) HSPC proliferation, self-renewal and maintenance, up-regulation of HOX B3, B4 and A9 and down-regulation of HOX B8 and A10 gene expression.

Vascular stem cells and ischaemic retinopathies

Retinal ischaemic disorders such as diabetic retinopathy and retinal vein occlusion are common. The hypoxia-related stimuli from oxygen-deprived neural and glial networks can drive expression of growth factors and cytokines which induce leakage from the surviving vasculature and/or pre-retinal and papillary neovascularisation. If left untreated, retinal vascular stasis, hypoxia or ischaemia can lead to macular oedema or fibro-vascular scar formation which are associated with severe visual impairment, and even blindness. Current therapies for ischaemic retinopathies include laser photocoagulation, injection of corticosteroids or VEGF-antibodies and vitreoretinal surgery, however they carry significant side effects. As an alternative approach, we propose that if reparative intra-retinal angiogenesis can be harnessed at the appropriate stage, ischaemia could be contained or reversed. This review provides evidence that reperfusion of ischaemic retina and suppression of sight-threatening sequelae is possible in both experimental and clinical settings. In particular, there is emphasis on the clinical potential for endothelial progenitor cells (EPCs) to promote vascular repair and reversal of ischaemic injury in various tissues including retina. Gathering evidence from an extensive published literature, we outline the molecular and phenotypic nature of EPCs, how they are altered in disease and provide a rationale for harnessing the vascular reparative properties of various cell sub-types. When some of the remaining questions surrounding the clinical use of EPCs are addressed, they may provide an exciting new therapeutic option for treating ischaemic retinopathies. (C) 2011 Elsevier Ltd. All rights reserved.