Flotillin-1-enriched lipid raft domains accumulate on maturing phagosomes

Flotillin-1 was recently shown to be enriched on detergent-resistant domains of the plasma membrane called lipid rafts. These rafts, enriched in sphingolipids and cholesterol, sequester certain proteins while excluding others. Lipid rafts have been implicated in numerous cellular processes including signal transduction, membrane trafficking and molecular sorting. In this study, we demonstrate both morphologically and biochemically that lipid rafts are present on phagosomes, These structures are enriched in flotillin-1 and devoid of the main phagosomes membrane protein lysosomal-associated membrane protein (LAMP1), The flotillin-1 present on phagosomes does not originate from the plasma membrane during phagocytosis but accumulates gradually on maturing phagosomes, Treatment with bafilomycin A1, a compound that inhibits the proton pump ATPase and prevents the fusion of phagosomes with late endocytic organelles, prevents the acquisition of flotillin-1 by phagosomes, indicating that this protein might be recruited on phagosomes from endosomal organelles. A proteomic characterization of the lipid rafts of phagosomes indicates that actin, the alpha- and beta -subunits of heterotrimeric G proteins, as well as subunits of the proton pump V-ATPase are among the constituents of these domains. Remarkably, the intracellular parasite Leishmania donovani can actively inhibit the acquisition of flotillin-1-enriched lipid rafts by phagosomes and the maturation of these organelles. These results indicate that specialized functions required for phagolysosome biogenesis may occur at focal points on the phagosome membrane, and therefore represent a potential target of intracellular pathogens.

Human cortical processing of colour and pattern

The present study investigates human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that we specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. We did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. We found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions. (C) 2001 Wiley-Liss, Inc.

GLUT4 - At the cross roads between membrane trafficking and signal transduction

GLUT4 is a mammalian facilitative glucose transporter that is highly expressed in adipose tissue and striated muscle. In response to insulin, GLUT4 moves from intracellular storage areas to the plasma membrane, thus increasing cellular glucose uptake. While the verification of this 'translocation hypothesis' (Cushman SW. Wardzala LJ. J Biol Chem 1980;255: 4758-4762 and Suzuki K, Kono T. Proc Natl Acad Sci 1980;77: 2542-2545) has increased our understanding of insulin-regulated glucose transport, a number of fundamental questions remain unanswered. Where is GLUT4 stored within the basal cell? How does GLUT4 move to the cell surface and what mechanism does insulin employ to accelerate this process) Ultimately we require a convergence of trafficking studies with research in signal transduction. However, despite more than 30 years of intensive research we have still not reached this point. The problem is complex, involving at least two separate signal transduction pathways which feed into what appears to be a very dynamic sorting process. Below we discuss some of these complexities and highlight new data that are bringing us closer to the resolution of these questions.

Enabling computer access: Introduction to the Test of Mouse Proficiency

As the use of technological devices in everyday environments becomes more prevalent, it is clear that access to these devices has become an important aspect of occupational performance. Children are increasingly required to competently manipulate technology such as the computer to fulfil occupational roles of student and player. Occupational therapists are in a position to facilitate the successful interface between children and standard computer technologies. The literature has supported the use of direct manipulation interfaces in computing that requires mastery of devices such as the mouse. Identification of children likely to experience difficulties with mouse use will inform the development of appropriate methods of intervention promoting mouse skill and further enhance participation in occupational tasks. The aim of this paper is to discuss the development of an assessment of mouse proficiency for children. It describes the construction of the assessment, the content of the test, and its content validity.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

A rapid screen of the severity of mild traumatic brain injury

This study investigated the sensitivity of information processing, recall and orientation tasks to the presence of mild Traumatic Brain Injury (mTBI). Fifty-six (40 male, 16 female) mTBI patients and 85 (57 male and 28 female) controls with orthopaedic injuries were tested within 24 hr of injury in the Department of Emergency Medicine. mTBI patients answered fewer orientation questions and recalled fewer words in delayed recall than orthopaedic patients. mTBI patients judged fewer sentences in 2 min than orthopaedic controls, and female mTBI patients judged fewer sentences than male mTBI patients. Male mTBI patients correctly recalled fewer words during immediate memory and learning than female mTBI patients and orthopaedic controls. Those mTBI patients with a history of previous head injuries did not perform more poorly than those mTBI patients without previous head injuries. These results indicate that tests of speed of information processing, word learning and orientation questions are sensitive to the acute effects of mTBI.

Theory of mind and peer acceptance in preschool children

Two studies tested the hypothesis that preschool children's theory of mind ability is related to their levels of peer acceptance. In Study 1, 78 children between the ages of 4 and 6 provided peer nominations that allowed determination of social preference and social impact scores, and classification in one of five peer status groups (following Coie & Dodge, 1983). Children were also tested on five different theory of mind tasks. The results showed that theory of mind scores were significantly related to social preference scores in a subsample of children who were over 5 years old. Further, popular children were found to score higher on theory of mind tasks than children classified as rejected. Study 2 replicated and extended the first study with a new sample of 87 4- to 6-year-old children. Study 2 included measures of peer acceptance, theory of mind ability and verbal intelligence, as well as teacher ratings of prosocial and aggressive behaviours. The results of Study 2 showed that for the total group of children, prosocial behaviour was the best predictor of social preference scores. When the Study 2 sample was split into older and younger children, theory of mind ability was found to be the best predictor of social preference scores for the older children (over age 5), while aggressive and prosocial behaviours were the best predictors of peer acceptance in the younger children. Overall, the pattern of results suggests that the impact of theory of mind ability on peer acceptance is modest but increases with children's age.

Probing the time course of nonlinear discriminations during human electrodermal conditioning

Animal-based theories of Pavlovian conditioning propose that patterning discriminations are solved using unique cues or immediate configuring. Recent studies with humans, however, provided evidence that in positive and negative patterning two different rules are utilized. The present experiment was designed to provide further support for this proposal by tracking the time course of the allocation of cognitive resources. One group was trained in a positive patterning; schedule (A-, B-, AB+) and a second in a negative patterning schedule (A+, B+, AB-). Electrodermal responses and secondary task probe reaction time were measured. In negative patterning, reaction times were slower during reinforced stimuli than during non-reinforced stimuli at both probe positions while there were no differences in positive patterning. These results support the assumption that negative patterning is solved using a rule that is more complex and requires more resources than does the rule employed to solve positive patterning. (C) 2001 Elsevier Science (USA).

Spontaneous and reflexive eye activity measures of mental workload

Measures of eye activity, such as blink rate and scanning patterns, have been used extensively as psychophysiological indices of mental workload. In a review of measures derived from spontaneous eye activity it is shown that different measures are differentially sensitive to specific aspects of mental workload. A less well-known measure of non-spontaneous eye activity, the blink reflex, is also reviewed. Experiments using discrete punctuate stimuli and continuous tasks analogous to real-world systems show that blink reflexes are modulated by attention and that this modulation reflects modality-specific attentional engagement. Future research should examine the utility of the blink reflex according to the desirable properties of sensitivity, diagnosticity, validity, reliability, ease of use, unobtrusiveness, and operator acceptance.

Perception or synthesized voice quality in connected speech by Cantonese speakers

Perceptual voice analysis is a subjective process. However, despite reports of varying degrees of intrajudge and interjudge reliability, it is widely used in clinical voice evaluation. One of the ways to improve the reliability of this procedure is to provide judges with signals as external standards so that comparison can be made in relation to these anchor signals. The present study used a Klatt speech synthesizer to create a set of speech signals with varying degree of three different voice qualities based on a Cantonese sentence. The primary objective of the study was to determine whether different abnormal voice qualities could be synthesized using the built-in synthesis parameters using a perceptual study. The second objective was to determine the relationship between acoustic characteristics of the synthesized signals and perceptual judgment. Twenty Cantonese-speaking speech pathologists with at least three years of clinical experience in perceptual voice evaluation were asked to undertake two tasks. The first was to decide whether the voice quality of the synthesized signals was normal or not. The second was to decide whether the abnormal signals should be described as rough, breathy, or vocal fry. The results showed that signals generated with a small degree of aspiration noise were perceived as breathiness while signals with a small degree of flutter or double pulsing were perceived as roughness. When the flutter or double pulsing increased further, tremor and vocal fry, rather than roughness, were perceived. Furthermore, the amount of aspiration noise, flutter, or double pulsing required for male voice stimuli was different from that required for the female voice stimuli with a similar level of perceptual breathiness and roughness. These findings showed that changes in perceived vocal quality could be achieved by systematic modifications of synthesis parameters. This opens up the possibility of using synthesized voice signals as external standards or anchors to improve the reliability of clinical perceptual voice evaluation. (C) 2002 Acoustical Society of America.

Well-formedness judgment: A comparison of offline and online performance in Broca's aphasics

0na eg rcarmitimcaal tfieca tcuorem opfr ethhee nospieornat iodneafli cdietf i(nAitiCoDn )o ft hthaet frequently co-occurs with Broca’s aphasia is above-chance performance on well-formedness judgment tasks for many syntactic constructions, but impaired performance where syntactic binding of traces to their antecedents occurs. However, the methodologies used to establish this aspect of the performance profile of the ACD have been predominantly offline. Offline well-formedness tasks entail extralinguistic processing (e.g. perception, attention, short-term memory, conscious reflection) in varying amounts and the influence of such processes on parsing mechanisms is yet to be fully established. In order to (a) further understand the role of extra-linguistic processing on parsing, and (b) gain a more direct insight into the online nature of parsing in Broca’s aphasia, 8 subjects underwent a series of wellformedness judgment investigations using both offline and online test batteries. The sentence types and error types used were motivated by three current theories about the nature of the ACD, namely, the Trace-Based Account (Grodzinsky, 2000), the Mapping Hypothesis (Linebarger et al., 1983) and Capacity proposals (e.g. Frazier & Friederici, 1991). The results from the present investigation speak directly to the three aforementioned theories and also demonstrate the important role that extralinguistic processing plays during offline assessment. The clinical implications of the different outcomes from the offline vs. online tasks are also discussed.

The influence of preparedness on rapid stepping in young and older adults

Objective: To investigate the influence of age and preparation level on postural muscle activation and step completion time during a rapid step task. Design: Postural muscle onset times (EMG) and ground reaction forces were recorded from healthy young (n = 20, age 21 +/- 3 years) and older (n = 25, age 71 +/- 5 years) female adults during a choice reaction-time stepping paradigm. Main outcome measures: Onset times of six trunk and hip muscles, reaction time and components of the step (weight shift time, step time and task time) were recorded. Results: Muscle activation was delayed and movement time was lengthened in both young and older adults when poorly prepared for a stepping task. While reduced preparation did not influence older adults to a greater extent than young adults, the slowest step response and completion time was evident in older adults when poorly prepared to move. Conclusions: A late postural response when poorly prepared to move may be a contributing factor to an increased risk of overbalancing in older adults. Future assessment of and intervention to improve postural stability in older adults should be expanded to incorporate tasks performed at various levels of preparation.

The influence of a concurrent cognitive task on the compensatory stepping response to a perturbation in balance-impaired and healthy elders

This study investigated the influence of a concurrent cognitive task on the compensatory stepping response in balance-impaired elders and the attentional demand of the stepping response. Kinetic, kinematic and neuromuscular measures of a forward recovery step were investigated in 15 young adults, 15 healthy elders and 13 balance-impaired elders in a single task (postural recovery only) and dual task (postural recovery and vocal reaction time task) situation. Results revealed that reaction times were longer in all subjects when performed concurrently with a compensatory step, they were longer for a step than an in-place response and longer for balance-impaired older adults compared with young adults. An interesting finding was that the latter group difference may be related to prioritization between the two tasks rather than attentional demand, as the older adults completed the step before the reaction time, whereas the young adults could perform both concurrently. Few differences in step characteristics were found between tasks, with the most notable being a delayed latency and reduced magnitude of the early automatic postural response in healthy and balance-impaired elders with a concurrent task. (C) 2002 Elsevier Science B.V. All rights reserved.

Effect of varying levels of mental workload on startle eyeblink modulation

Previous research using punctuate reaction time and counting tasks has found that the startle eyeblink reflex is sensitive to attentional demands. The present experiment explored whether startle eyeblink is also modulated during a complex continuous task and is sensitive to different levels of mental workload. Participants (N=14) performed a visual horizontal tracking task either alone (single-task condition) or in combination with a visual gauge monitoring task (multiple-task condition) for three minutes. On some task trials, the startle eyeblink reflex was elicited by a noise burst. Results showed that startle eyeblink was attenuated during both tasks and that the attenuation was greater during the multiple-task condition than during the single-task condition. Subjective ratings, endogenous eyeblink rate, heart period, and heart period variability provided convergent validity of the workload manipulations. The findings suggest that the startle eyeblink is sensitive to the workload demands associated with a continuous visual task. The application of startle eyeblink modulation as a workload metric and the possibility that it may be diagnostic of workload demands in different stimulus modalities is discussed.

Drawing insight from pictures: The development of concepts of false drawing and false belief in children with deafness, normal hearing, and autism

Theory-of-mind concepts in children with deafness, autism, and normal development (N = 154) were examined in three experiments using a set of standard inferential false-belief tasks and matched sets of tasks involving false drawings. Results of all three experiments replicated previously published findings by showing that primary school children with deafness or autism, aged 6 to 13 years, scored significantly lower than normal-developing 4-year-old preschoolers on standard misleading-container and unseen-change tests of false-belief understanding. Furthermore, deaf and autistic children generally scored higher on drawing-based tests than on corresponding standard tests and, on the most challenging of the false-drawing tests in Experiment 2, they significantly outperformed the normal-developing preschoolers by clearly understanding their own false intentions and another person's false beliefs about an actively misleading drawing. In Experiment 3, preschoolers; outperformed older deaf and autistic children on standard tasks, but did less well on a task that required the drawing of a false belief. Methodological factors could not fully explain the findings, but early social and conversational experiences in the family were deemed likely contributors.