Beginning readers' use of orthographic analogies in word reading

This research re-investigated the claim that beginning readers exploit information from the orthographic rime of clue words to help them to decode unfamiliar words. In Experiment 1, first-grade children were equally able to use orthographic information from the beginning, middle, and end of clue words to identify unfamiliar target words. Moreover, the improvement in reading end- (or orthographic rime-) same target words following clue word presentation reflected phonological priming. In second-grade children, with correction for retesting effects, improvement following clue word presentation for end-same and beginning-same target words was equivalent, although end-same target words improved more than middle-same target words. In Experiment 2, both first- and second-grade children were able to use orthographic information from the beginning, middle, and end of clue words to identify unfamiliar words. Clue word presentation enhanced the reading of beginning-same and end-same target words more than middle-same target words. Improvement was the same for beginning-same and end-same target words. Target word improvement following clue word presentation was greater than that for phonologically primed words only in children reading target words sharing the beginning sequence of the clue word. (C) 1998 Academic Press.

Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times. (C) 1999 Elsevier Science B.V. All rights reserved.

Lentiviral vector-mediated tyro sinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a vital role in primary immune responses. Introducing genes into DCs will allow constitutive expression of the encoded proteins and thus prolong the presentation of the antigens derived therefrom. In addition, multiple and unidentified epitopes encoded by the entire tumor-associated antigen (TAA) gene may enhance T cell activation. This study demonstrated that an HIV-1-based lentiviral vector conferred efficient gene transfer to DCs. The transgene, murine tyrosinase-related protein 2 (mTRP-2), encodes a clinically relevant melanoma-associated antigen (MAA), which has been found to be a tumor rejection antigen for B16 melanoma. The transfer and proper processing of mTRP-2 in DCs, in terms of RNA transcription activity and protein expression, were verified by RT-PCR and specific antibody, respectively. Administration of mTRP-2 gene-modified DCs (DC-HR'CmT2) to C57BL/6 mice evoked strong protection against tumor challenge, for which the presence of CD4(+) and CD8(+) cells during both the priming and challenge phase was essential. In a therapy model, our results showed that four of seven mice with preestablished tumor remained tumor free for 80 days after therapeutic vaccination. Given the results shown in this study, mTRP-2 gene transfer to DCs provides a potential therapeutic strategy for the management of melanoma, especially in the early stage of the disease.

CD40 ligation conditions dendritic cell antigen-presenting function through sustained activation of NF-kappa B

An understanding of the biochemical control of dendritic cell (DC) differentiation/activation is essential for improving T cell immunity by various immunotherapeutic approaches, including DC immunization. Ligation of CD40 enhances DC function, including conditioning for CTL priming. NF-kappaB, and particularly RelB, is an essential control pathway for myeloid DC differentiation. Furthermore, RelB regulates B cell Ag-presenting function. We hypothesized that CD40 ligand (CD40L) and TNF-alpha, which differ in their capacity to condition DC, would also differ in their capacity to activate NF-kappaB. DC differentiated for 2 days from monocytes in the presence of GM-CSF and IL-4 were used as a model, as NF-kappaB activity was constitutively low. The capacity of DC to activate T cells following CD40L treatment was enhanced compared with TNF-alpha treatment, and this was NF-kappaB dependent. Whereas RelB/p50 translocation induced by TNF-alpha was attenuated after 6 h, RelB/p50 nuclear translocation induced by CD40L was sustained for at least 24 h. The mechanism of this difference related to enhanced degradation of IkappaBalpha following CD40L stimulation. However, NF-kappaB activation induced by TNF-alpha could be sustained by blocking autocrine IL-10. These data indicate that NF-kappaB activation is essential for T cell activation by DC, and that this function is enhanced if DC NF-kappaB activation is prolonged. Because IL-10 moderates DC NF-kappaB activation by TNF-alpha, sustained NF-kappaB activation can be achieved by blocking IL-10 in the presence of stimuli that induce TNF-alpha.

Antigen-specific suppression of inflammatory arthritis by dendritic cells

Purpose Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. We have shown that NF-κB inactivation in dendritic cells (modified DC) converts them into cells that tolerize rather than immunize to specific antigen [1]. Antigen-exposed modified DC prevent priming of immunity, and they suppress previously primed immune responses. Regulatory CD4+ T cells, which can transfer antigen-specific tolerance in an IL-10-dependent fashion, mediate the tolerance. We hypothesized that modified DC exposed to arthritogenic antigen would suppress clinical arthritis after disease onset. Methods Antigen-induced arthritis was induced in C57/Bl6 mice by priming to methylated bovine serum albumin (mBSA) antigen followed by challenge injection of mBSA to one knee. Knee swelling was apparent within 2 days, with peak clinical signs apparent at 5 days. Mice were treated with antigen-exposed modified DC between 2 and 6 days after mBSA challenge to the knee joint. Results Clinical arthritis was suppressed in each group receiving mBSA-exposed modified DC within 4 days compared with mice that received either no DC or keyhole limpet hemocyanin-exposed modified DC. Clinical improvement was associated with mBSA-specific tolerance in mice receiving mBSA-exposed modified DC. Tolerance induction was not impaired by concomitant administration of anti-tumor necrosis factor alpha monoclonal antibody. Subsequent rechallenge with intra-articular IL-1 induced flare of arthritis in all groups, which could be effectively suppressed by a second administration of mBSA-exposed modified DC. Conclusions The data indicate that modified DC induce antigen-specific immune suppression in this model of inflammatory arthritis, even after full clinical expression of the disease. These observations have important implications for antigen-specific therapy of autoimmunity.

Aquisition and extinction of two characteristics consistent with fear relevance

Fear relevance, the potential of a stimulus to become quickly associated with fear, is a characteristic assumed to have an evolutionary basis and to result in preferential processing. Previous research has shown that fear relevant stimuli share a number of characteristics, negative valence and preferential identification in a visual search task, for instance. The present research examined whether these two characteristics can be acquired by non-fear relevant stimuli (geometric shapes) as a result of Pavlovian fear conditioning. Two experiments employed an aversive learning paradigm with geometric shape CSs and a shock US, with stimulus ratings, affective priming and visual search performance assessed before and after acquisition and after extinction. Differential electrodermal responses, larger during CS1 than CS, were present during acquisition but not during extinction. Affective priming results suggest that the CS1 acquired negative valence during acquisition, which was lost during extinction. However, negative valence as indexed by more negative ratings for CS1 than for CS shapes seemed to survive extinction. Preferential attentional processing as indexed by faster detection of CS1 among CS shapes than vice versa on the visual search task also remained. The current research confirmed that characteristics of fear relevant stimuli can be acquired in an aversive learning episode and that they may be extinguished. This supports the proposal that fear relevance may be malleable through learning.

Extinction of affective learning: No evidence for dual process accounts of human learning

The acquisition and extinction of affective valence to neutral geometrical shape conditional stimuli was investigated in three experiments. Experiment 1 employed a differential conditioning procedure with aversive shock USs. Differential electrodermal responding was evident during acquisition and lost during extinction. As indexed by verbal ratings, the CS1 acquired negative valence during acquisition,which was reduced after extinction. Affective priming, a reaction time based demand free measure of stimulus valence, failed to provide evidence for affective learning. Experiment 2 employed pictures of happy and angry faces as USs.Valence ratings after acquisitionweremore positive for theCS paired with happy faces (CS-H) and less positive for the CS paired with angry faces (CS-A) than during baseline. Extinction training reduced the extent of acquired valence significantly for both CSs, however, ratings of the CS-A remained different from baseline. Affective priming confirmed these results yielding differences between CS-A and CS-H after acquisition for pleasant and unpleasant targets, but for pleasant targets only after extinction. Experiment 3 replicated the design of Experiment 2, but presented the US pictures backwardly masked. Neither rating nor affective priming measures yielded any evidence for affective learning. The present results confirm across two different experimental procedures that, contrary to predictions from dual process accounts of human learning, affective learning is subject to extinction.

The psychophysiology of anticipation

The current research explored the processes that predominate during the anticipation of an emotionally salient event. Experiment 1 (N536), employed three different conditional stimuli followed by pictorial pleasant, unpleasant or neutral unconditioned stimuli. Half the participants were trained with visual CSs, the other half with tactile CSs. In the group trained with visual CSs, startle eyeblinks were larger and faster during CSs that were paired with unpleasant pictures than CSs paired with neutral or pleasant pictures respectively, indicating an affect startle pattern. This linear trend was not found in the group trained with tactile CSs. Experiment 2 (N564) aimed to investigate whether the affective pattern found in the startle data in Experiment 1 could also be found using a behavioural measure of emotion. This time participants’ reaction time during a post-experimental affective priming taskwas used as dependantmeasure to assess the presence of emotional learning. Instead of a simple differential conditioning task, an occasion setting paradigm was employed and participants were trained using either a feature positive or feature negative design with pleasant or unpleasant picture USs. For participants trained with unpleasant USs, valence ratings collected before and after conditioning training suggested the presence of emotional learning, whereas no such pattern was found for participants trained with pleasant USs. These findings were not confirmed in the priming data.

Alleviation of dormancy in annual ryegrass (Lolium rigidum) seeds by hydration and after-ripening

The effect of hydration (priming) treatment on dormancy release in annual ryegrass seeds from two populations was investigated. Hydration duration, number, and timing with respect to after-ripening were compared in an experiment involving 15 treatment regimens for 12 wk. Seeds were hydrated at 100% relative humidity for 0, 2, or 10 d at Weeks 1, 6, or 12 of after-ripening. Dormancy status was assessed after each hydration treatment by measuring seed germination at 12-hourly alternating 25/15 C (light/dark) periods using seeds directly from the hydration treatment and seeds subjected to 4 d postpriming desiccation. Seeds exposed to one or more hydration events during the 12 wk were less dormant than seeds that remained dry throughout after-ripening. The longer hydration of 10 d promoted greater dormancy loss than either a 2-d hydration or no hydration. For the seed lot that was most dormant at the start of the experiment, two or three rather than one hydration event or a hydration event earlier rather than later during after-ripening promoted greater dormancy release. These effects were not significant for the less-dormant seed lot. For both seed lots, the effect of a single hydration for 2 d at Week 1 or 6 of after-ripening was not manifested until the test at Week 12 of the experiment, suggesting that the hydration events alter the rate of dormancy release during subsequent after-ripening. A hydrothermal priming time model, usually used for modeling the effect of priming on germination rate of nondormant seeds, was successfully applied to dormancy release resulting from the hydration treatments.

Why fear snakes and spiders? Evidence for a learning-based account of fear-relevant stimulus-processing

Fear-relevant stimuli, such as snakes, spiders and heights, preferentially capture attention as compared to nonfear-relevant stimuli. This is said to reflect an encapsulated mechanism whereby attention is captured by the simple perceptual features of stimuli that have evolutionary significance. Research, using pictures of snakes and spiders, has found some support for this account; however, participants may have had prior fear of snakes and spiders that influenced results. The current research compared responses of snake and spider experts who had little fear of snakes and spiders, and control participants across a series of affective priming and visual search tasks. Experts discriminated between dangerous and nondangerous snakes and spiders, and expert responses to pictures of nondangerous snakes and spiders differed from those of control participants. The current results dispute that stimulus fear relevance is based purely on perceptual features, and provides support for the role of learning and experience.

The role of CD4 T help in multiple vaccinations when using minimal CD8 T cell epitope peptides

Background: The fact that some cancers and viral infections can be controlled by effector CD8 T cells led to the possibility of utilising minimal CD8 T cell epitope peptides as vaccines. However using minimal CD8 T cell epitope peptide immunisations and a tumour protection model in mice, we have previously shown that functional memory CD8 T cells are not generated unless CD4 T help is provided at the time of CD8 T cell priming. Short-lived effector cells nevertheless are generated in the absence of T help. Aim: To determine the role of CD4 T help in multiple immunisations. Method: Minimal CD8 T cell peptides of HPV16 E7 protein and Ovalbumin were used (with adjuvants Quil-A or IFA) as immunogens in C57BL mice. The presence of effector CD8 T cells were determined by tumour protection assays and was quantified by IFN-gamma ELISPOT assays. Results: In the present study we show that unless T help is provided at the time CD8 T cells are primed, no CD8 effector cells are generated when boosted with the vaccine again in the absence of T help. Our results further show that this failure could be prevented by the inclusion of a T helper peptide during the primary or booster immunisations.

B, NK and NKT cells contribute to suppression of immunity by dendritic cells

Among the population of antigen presenting cells, dendritic cells (DCs) are considered the sentinels of the immune system. Besides activating naı¨ ve T cells, DC can directly activate naı¨ ve and memory B cells and are also able to regulate effectors of innate immunity such as NK cells and NKT cells. Increasing evidence indicates that DCs are not only decisive for T cell priming, but are also key players to maintain self-tolerance in vivo. Previous results in our lab have shown that DCs treated with a pharmacological NFkB inhibitor (BAY11–7082) confer suppression to a previously immune response. This suppression was IL-10 dependent and results from the induction of Ag specific CD4+ regulatory T cells. To elucidate the mechanism of suppression induced by administration of Bay treated DC, we used a model of infectious tolerance transfer from DC treated mice to primed recipient mice. Our results show that both CD4 + splenic cells and non T cells from animals injected with Bay treated DC, but not from untreated DC, were capable of transferring the suppression. Moreover, sorted B cells and NK cells could transfer antigenspecific infectious tolerance after administration of Bay treated DC. In addition, this suppressive effect could not be seen either in mice depleted of NK cells nor in NKT deficient mice. These observations highlight the role of several immune cells in the maintenance of tolerance, and impact on the design of immunotherapeutic suppression of autoimmune diseases in which NKT cells are deficient or defective, such as diabetes and lupus.

Cue exposure in moderation drinking: A comparison with cognitive-behavior therapy

To date, the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal. A modification of cue exposure (CE) for moderation drinking, which incorporated priming doses of alcohol, could train participants to stop drinking after 2 to 3 drinks. This study examined the effects of modified CE within sessions, combined with directed homework practice. Nondependent problem drinkers who requested a moderation drinking goal were randomly allocated to modified CE or standard cognitive-behavior therapy (CBT) for alcohol abuse. Both interventions were delivered in 6 90-min group sessions. Eighty-one percent of eligible participants completed treatment and follow-up assessment. Over 6 months, CE produced significantly greater reductions than CBT in participants' reports of drinking frequency and consumption on each occasion. No pretreatment variables significantly predicted outcome, The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal.

Expecting dirt but saying dart: The creation of a blend memory

During a naming task, time pressure and a manipulation of the proportion of related prime-target pairs were used to induce subjects to generate an expectation to the prime. On some trials, the presented target was orthographically and generally phonologically similar to the expected tal-get. The expectancy manipulation was barely detectable in the priming data but was clearly evident on a final recognition test. In addition, the recognition data showed that the nearly simultaneous activation of an expectation and sensory information derived from the orthographically and phonologically similar target produced a false memory. It is argued that this represents a blend memory.

Lexical decision in Parkinson's disease: A reply to Brown, McDonald, and Spicer (1999)

Recent semantic priming investigations in Parkinsons disease (PD) employed variants of Neelys (1977) lexical decision paradigm to dissociate the automatic and attentional aspects of semantic activation (McDonald, Brown, Gorell, 1996; Spicer, Brown, Gorell, 1994). In our earlier review, we claimed that the results of Spicer, McDonald and colleagues normal control participants violated the two-process model of information processing (Posner Snyder, 1975) upon which their experimental paradigm had been based (Arnott Chenery, 1999). We argued that, even at the shortest SOA employed, key design modifications to Neelys original experiments biased the tasks employed by Spicer et al. and McDonald et al. towards being assessments of attention-dependent processes. Accordingly, we contended that experimental procedures did not speak to issues of automaticity and, therefore, Spicer, McDonald and colleagues claims of robust automatic semantic activation in PD must be treated with caution.