Older adults with slow sit to stand times show reduced temporal precision of audio-visual integration.

Sustained integration of sensory inputs over increased temporal delays is associated with reduced cognitive and physical functioning in older adults and adverse outcomes such as falls. Here, we explored the relationship between multisensory integration and a clinically relevant measure of balance/postural control; Sit-to-Stand Time, the efficiency with which an older adult can transition between a seated and a standing posture. We investigated whether temporal multisensory integration was associated with performance on the Five-Times Sit-to-Stand Test (FTSST) in a large sample of 2556 older adults (mean age = 63.62 years, SD = 7.50; 55% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). K-means clustering was applied to FTSST data, yielding three clusters characterised by fast (mean = 10.88 s; n = 1122), medium (mean = 14.34 s; n = 1133) and slow (mean = 18.97 s; n = 301) sit-to-stand times. At wave 3 of TILDA, older adults participated in the Sound Induced Flash Illusion (SIFI), a measure of the precision of temporal audio-visual integration, which included three audio-visual stimulus onset asynchronies (SOAs): 70, 150 and 230 ms. Older adults with the slowest sit-to-stand times were more susceptible to the SIFI at the longest SOA (230 ms) compared to the shortest SOA (70 ms) relative to those with the fastest times (p = 0.02). Older adults who take longer to repeatedly transition from a seated to a standing posture exhibit an expanded temporal binding window for audio-visual events, supporting a link between multisensory perception and balance/postural control in ageing.

Self-reported vividness of tactile imagery for object properties and body regions: An exploratory study.

Mental imagery ability has been examined principally in the visual domain. Despite evidence for tactile mental representations in the absence of direct stimulation, this ability is poorly understood. We investigated tactile imagery for both active and passive tasks in a large sample (N = 118). Vividness of imagery was tested across two different tasks: somatosensory imagery (of body sensitivity) and tactile imagery (of object properties) in all participants. Evidence for vivid imagery across tactile and somatosensory dimensions was found with a positive, albeit weak, correlation in imagery strength between dimensions. Imagery ratings varied across objects and object properties in the tactile imagery task and across body sites in the somatosensory imagery task. These findings shed light on the capacity for, and characteristics of, tactile mental imagery in the general population and suggest that the ability to experience vivid tactile mental images may mediate performance across a number of perceptual tasks.

Generalisation to novel exemplars of learned shape categories based on visual and auditory spatial cues does not benefit from multisensory information.

Although the integration of information across multiple senses can enhance object representations in memory, how multisensory information affects the formation of categories is uncertain. In particular, it is unclear to what extent categories formed from multisensory information benefit object recognition over unisensory inputs. Two experiments investigated the categorisation of novel auditory and visual objects, with categories defined by spatial similarity, and tested generalisation to novel exemplars. Participants learned to categorise exemplars based on visual-only (geometric shape), auditory-only (spatially defined soundscape) or audio-visual spatial cues. Categorisation to learned as well as novel exemplars was then tested under the same sensory learning conditions. For all learning modalities, categorisation generalised to novel exemplars. However, there was no evidence of enhanced categorisation performance for learned multisensory exemplars. At best, bimodal performance approximated that of the most accurate unimodal condition, although this was observed only for a subset of exemplars within a category. These findings provide insight into the perceptual processes involved in the formation of categories and have relevance for understanding the sensory nature of object representations underpinning these categories.

Multisensory perception constrains the formation of object categories: a review of evidence from sensory-driven and predictive processes on categorical decisions.

Although object categorization is a fundamental cognitive ability, it is also a complex process going beyond the perception and organization of sensory stimulation. Here we review existing evidence about how the human brain acquires and organizes multisensory inputs into object representations that may lead to conceptual knowledge in memory. We first focus on evidence for two processes on object perception, multisensory integration of redundant information (e.g. seeing and feeling a shape) and crossmodal, statistical learning of complementary information (e.g. the 'moo' sound of a cow and its visual shape). For both processes, the importance attributed to each sensory input in constructing a multisensory representation of an object depends on the working range of the specific sensory modality, the relative reliability or distinctiveness of the encoded information and top-down predictions. Moreover, apart from sensory-driven influences on perception, the acquisition of featural information across modalities can affect semantic memory and, in turn, influence category decisions. In sum, we argue that both multisensory processes independently constrain the formation of object categories across the lifespan, possibly through early and late integration mechanisms, respectively, to allow us to efficiently achieve the everyday, but remarkable, ability of recognizing objects. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Longitudinal grip strength is associated with susceptibility to the Sound Induced Flash Illusion in older adults.

The precision of temporal multisensory integration is associated with specific aspects of physical functioning in ageing, including gait speed and incidents of falling. However, it is unknown if such an association exists between multisensory integration and grip strength, an important index of frailty and brain health and predictor of disease and mortality in older adults. Here, we investigated whether temporal multisensory integration is associated with longitudinal (eight-year) grip strength trajectories in a large sample of 2,061 older adults (mean age = 64.42 years, SD = 7.20; 52% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Grip strength (kg) for the dominant hand was assessed with a hand-held dynamometer across four testing waves. Longitudinal k-means clustering was applied to these data separately for sex (male, female) and age group (50-64, 65-74, 75+ years). At wave 3, older adults participated in the Sound Induced Flash Illusion (SIFI), a measure of the precision of temporal audio-visual integration, which included three audio-visual stimulus onset asynchronies (SOAs): 70, 150 and 230 ms. Results showed that older adults with a relatively lower (i.e., weaker) grip strength were more susceptible to the SIFI at the longer SOAs compared to those with a relatively higher (i.e., stronger) grip strength (p <.001). These novel findings suggest that older adults with relatively weaker grip strength exhibit an expanded temporal binding window for audio-visual events, possibly reflecting a reduction in the integrity of the central nervous system.

The rubber hand illusion is influenced by self-recognition.

Susceptibility to the Rubber Hand Illusion (RHI) demonstrates that body ownership can be modulated by visuotactile inputs. In contrast to body-like images, other objects cannot be embodied suggesting that crossmodal interactions on body ownership are based on a 'goodness-of-fit' mechanism relative to one's own body. However, it is not clear whether visual self-recognition influences susceptibility to the RHI, although evidence for individual differences in the perceptual body image on the RHI suggests that this may be the case. We investigated the role of self-recognition on the subjective experience of the RHI and measured proprioceptive drift and onset time of the RHI between two groups, one with the ability to identify an image of their own hand and the other without this ability. A typical RHI response was found overall with no group difference in the subjective experience of the RHI. However, a larger proprioceptive drift and an earlier onset time for the RHI was found for the non-recognisers than the self-recognition group. Our findings provide evidence for a link between a visual representation of one's own body in long-term memory and plasticity of the body representation.

Fine mapping of the binding sites of monoclonal antibodies raised against the Pk tag.

The monoclonal antibody (mAb) SV5-Pk is used widely in a variety of procedures to detect recombinant proteins tagged with the Pk tag, a 14 amino acid sequence derived from the P and V proteins of the paramyxovirus Simian Virus 5. Here we report on the isolation and characterisation of four additional SV5-Pk mAbs (termed SV5-Pk2 to 5) that bind the Pk tag. All the SV5-Pk mAbs can detect Pk tagged recombinant proteins in a variety of immunological procedures, including ELISA and immunofluorescence. Using SPOT technology, the minimal binding epitope of each SV5-Pk mAb was defined by one-sided terminal truncation analysis from either the amino- or carboxy-ends of the Pk peptide. Each mAb recognises slightly different epitopes within the Pk tag, ranging from 5 to 9 amino acids in length. The equilibrium dissociation constants (Kd) of the mAbs, as measured by surface plasmon resonance, ranged from approximately 20 to 60 pmol. Cysteine scanner mutations throughout the Pk tag revealed that some amino acids within the minimal binding epitopes were critical for mAb binding, while others could readily be substituted with little or no effect on antibody binding. The development of the Pk tag as a spacer arm for site-directed chemical coupling, and the use of the mAbs to monitor purification and coupling procedures, is discussed.

The effect of two novel analogues of antimycin A on oxygen consumption and survival of filarial nematodes in vitro.

The effects of two novel analogues of antimycin A (BWA466C and BWA728C) on filarial oxygen consumption, energy generation and survival were investigated in vitro. For comparison, incubations were performed with a range of mitochondrial respiration inhibitors. All compounds tested (rotenone, antimycin A, KCN, oligomycin, CCCP, rafoxanide, BWA466C and BWA728C) inhibited oxygen uptake. The two analogues were less potent than antimycin A at impairing respiration of either filariae or beef heart submitochondrial particles. However, the two compounds affected motility and were lethal in vitro. Although the analogues affected oxygen uptake similarly to antimycin A itself, the levels of ATP were significantly lower than those noted in the presence of antimycin A. Glucose consumption and lactate output were markedly reduced by BWA466C and BWA728C. Glucose transport (measured as 2-deoxy-[2,6-3H]glucose) was reduced after treatment with BWA728C. It is likely that a combination of the effects on glucose transport and inhibition of oxidative pathways of carbohydrate metabolism may lead to worm death in vitro.

Structure-activity relationships of antifilarial antimycin analogues: a multivariate pattern recognition study.

The structure-activity relationships of a series of novel antifilarial antimycin A1 analogues have been investigated by using computational chemistry and multivariate statistical techniques. The physiochemical descriptors calculated in this way contained information which was useful in the classification of compounds according to their in vitro antifilarial activity. This approach generated a 53 parameter descriptor set, which was reduced with a multivariate pattern recognition package, ARTHUR. Regression analysis of the reduced set yielded several statistically significant regression equations; e.g.-log in vitro activity = 0.017 mp + 0.65 log P - 0.81ESDL10-7.33 (R = 0.9). With use of this equation, it was possible to make predictions for further untested analogues. The analysis indicated that membrane or lipid solubility is an important determinant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake.

Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double blind study.

Prostaglandin E1 (PGE1) and prostacyclin have been used in Raynaud's phenomenon (RP) but are unstable and require intravenous administration. An alternative approach is to stimulate the body's own PGE1 production via administration of the precursor essential fatty acid. We studied the effect of 12 capsules/day of evening primrose oil (EPO) on the manifestations of RP. 21 patients received a two week course of placebo, thereafter 11 received EPO for 8 weeks and 10 patients received placebo. As the weather worsened the placebo group experienced significantly more attacks than the EPO group. Visual analogue scales assessing the severity of attacks and coldness of hands improved in the EPO group. No changes were seen in either group in hand temperatures and cold challenge plethysmography. Blood tests showed some antiplatelet effects of the drug. In conclusion patients receiving EPO benefited symptomatically. This was not matched however by any change in objective assessment of blood flow, although changes in platelet behaviour and blood prostanoids were observed.

Analysis of an H1 receptor-mediated, zinc-potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous vein.

The contractile action of the dipeptide carnosine (beta-alanyl-L-histidine), active as a Zn.carnosine complex (Zn. Carn), was investigated in isolated rings of rabbit saphenous vein (RSV) and was found to be antagonized by the H1 antagonist mepyramine. Mepyramine-sensitive, histamine-induced contractures in RSV, were smaller (73+/-0.1%) and less well sustained than carnosine-induced contractures. Schild plot values for mepyramine antagonism were, for carnosine-induced contractures; pA2 = 7.97+/-0.12, slope= 1.33+/-0.06 (r = 0.793) and for histamine-induced contractures; pA2 = 8.48+/-0.07, slope = 0.63+/-0.05, r = 0.957). Serotonergic antagonists methiothepin and ketanserin, antagonize both carnosine- and histamine-induced contractures in RSV, probably reflecting coincidental inhibition at the H1-receptor. Carnosine, with Zn present, can inhibit the H1-specific binding of [3H]-mepyramine to isolated guinea-pig cerebellar membranes (log IC50s - 2.78+/-0.02, -3.93+/-0.03 and -4.64+/-0.03 at 10, 30 and 80 microM Zn respectively; values corrected for the Zn-specific inhibition which has a logIC50 of -4.20). In the radioligand binding assay, the effect of carnosine can be described as a function of Zn. Carn concentration with an apparent logIC50 of -5.61. This value is consistent with that obtained from the functional studies on RSV. Histamine-induced contractures have an indomethacine-sensitive component (27.2+/-8.3% of control response), not apparent with carnosine-induced contractures. Like histamine, carnosine evoked an H2-mediated (cimetidine-sensitive) relaxation in the presence of mepyramine, but was less potent (10.8+/-3.1% residual tension at 10 mM carnosine compared with 13.4+7.5% at 0.1 mM histamine). Carnosine, like mepyramine, can 'reveal' the H2-mediated relaxation of histamine providing further evidence that carnosine binds at the H1 receptor. We conclude that carnosine can act at the smooth muscle H1-receptor to provoke vasoconstriction and that it also has the potential to act at H1-receptors in CNS.

Binding of immune complexes to Atlantic salmon peripheral blood leucocytes.

The ability of peripheral blood leucocytes (PBL) of Atlantic salmon to bind immune complexes in an antibody-dependent fashion was investigated. Immune complexes were labelled with fluorescein isothiocyanate and binding of these complexes to isolated PBL was determined by flow cytometry. The data show that a high proportion (up to 65%) of PBL were capable of binding immune complexes, and this binding did not occur when immune serum was replaced with normal serum. The presence of fresh normal serum inhibited or abrogated immune complex-binding of PBL. This is the first report of high levels of immune complex receptors on leucocytes in fish, and the dependence of complex binding on the presence of antibody suggests that these receptors may be similar to Fc receptors which are widely distributed on immunocytes of mammals.

The relationship between the adrenoceptor and nonadrenoceptor-mediated effects of imidazoline- and imidazole-containing compounds.

This article brings together work on imidazoline or imidazole-containing compounds concerned with the pharmacology of alpha-adrenoceptors, principally on smooth muscle, to illustrate how imidazolines have contributed to the subclassification of alpha-adrenoceptors and how, against this background, attempts have been made to use this knowledge to uncover "nonadrenoceptor"-mediated biological effects of previously uncharacterized compounds, notably imidazole-containing dipeptides and "clonidine displacing substance" (CDS). Recent data are included on (1) the pharmacology of UK-14304, (2) nonadrenoceptor actions of phentolamine, (3) the pharmacology of tissue extracts containing imidazole-containing dipeptides and CDS activity, and (4) ligand binding data at I1 and I2 sites.

Binding of soluble immune complexes to fractionated Atlantic salmon (Salmo salar L.) leucocytes.

Binding of a fluorescent-labelled soluble immune complex to different types of Atlantic salmon leucocytes was investigated using flow cytometry. Peripheral blood leucocytes (PBL) were separated into sIg+ and sIg enriched populations by magnetic activated cell sorting, blood neutrophils were identified by electronic gating, and kidney macrophages were selected by plastic-adherence. About 60% of both sIg+ and sIg- enriched PBL, 44% of neutrophils and 34% of macrophages bound the soluble immune complexes.

Abnormal biochemical and cellular parameters in the blood of patients with Raynauds phenomenon.

Finger blood flow is decreased in Raynauds Phenomenon (RP). This may be due not only to vasospasm, but also to blood abnormalities. 40 patients with Raynauds Disease (RD), 28 with suspected RP (SS) and 42 with secondary Raynauds syndrome (RS) were enrolled and compared to 50 controls. Results from base-line samples show that those with RP have abnormal haemostasis and rheology whereas those with mild Raynauds, RD do not. Blood sampled after cold challenge in 15 RS patients and 15 controls show that both groups exhibit platelet activation after emersion. The degree of activation however was much more marked in the RS patients. We have shown that abnormalities of haemostasis and rheology are found in patients likely to have endothelial damage (RS). These changes are probably a consequence rather than a cause of the disease. After cold challenge the results become more abnormal and correlate with severity of disease.

Parade and prejudice.

Nurses at Craigavon hospital near Drumcree braved bomb threats and violence during the Orange parades weekend to carry on with their work. Adrian O'Dowd was invited to join them.