Lipid and carbohydrate based adjuvant/carriers in immunology

This review discusses various issues regarding vaccines:what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest, in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.

Structural basis and prediction of substrate specificity in protein serine/threonine kinases

The large number of protein kinases makes it impractical to determine their specificities and substrates experimentally. Using the available crystal structures, molecular modeling, and sequence analyses of kinases and substrates, we developed a set of rules governing the binding of a heptapeptide substrate motif (surrounding the phosphorylation site) to the kinase and implemented these rules in a web-interfaced program for automated prediction of optimal substrate peptides, taking only the amino acid sequence of a protein kinase as input. We show the utility of the method by analyzing yeast cell cycle control and DNA damage checkpoint pathways. Our method is the only available predictive method generally applicable for identifying possible substrate proteins for protein serine/threonine kinases and helps in silico construction of signaling pathways. The accuracy of prediction is comparable to the accuracy of data from systematic large-scale experimental approaches.

Hemochromatosis and alcoholic liver disease

The close association of excessive alcohol consumption and clinical expression of hemochromatosis has been of widespread interest for many years. In most populations of northern European extraction, more than 90% of patients with overt hemochromatosis are homozygous for the C282Y mutation in the HFE gene. Nevertheless, the strong association of heavy alcohol intake with the clinical expression of hemochromatosis remains. We (individually or in association with colleagues from our laboratories) have performed three relevant studies in which this association was explored. In the first, performed in 1975 before the cloning of the HFE gene, the frequency of clinical symptoms and signs was compared in patients with classical hemochromatosis who consumed 100 g or more of alcohol per day versus in nondrinkers or moderate drinkers who consumed less than 100 g of alcohol per day. The results showed no difference between the two groups except for features of complications of alcoholism in the first group, especially jaundice, peripheral neuritis, and hepatic failure. Twenty-five percent of those with heavy alcohol consumption showed histologic features of alcoholic liver disease (including cirrhosis) together with heavy iron overload. It was concluded that these patients had the genetic disease complicated by alcoholic liver disease. In the second study (2002), 206 subjects with classical HFE-associated hemochromatosis in whom liver biopsy had been performed were evaluated to quantify the contribution of excess alcohol consumption to the development of cirrhosis in hemochromatosis. Cirrhosis was approximately nine times more likely to develop in subjects with hemochromatosis who consumed more than 60 g of alcohol per day than in those who drank less than this amount. In the third study (2002), 371 C282Y-homozygous relatives of patients with HFE-associated hemochromatosis were assessed. Eleven subjects had cirrhosis on liver biopsy and four of these drank 60 g or more of alcohol per day. The reason why heavy alcohol consumption accentuates the clinical expression of hemochromatosis is unclear. Increased dietary iron or increased iron absorption is unlikely. The most likely explanation would seem to be the added co-factor effect of iron and alcohol, both of which cause oxidative stress, hepatic stellate cell activation, and hepatic fibrogenesis. In addition, the cumulative effects of other forms of liver injury may result when iron and alcohol are present concurrently. Clearly, the addition of dietary iron in subjects homozygous for hemochromatosis would be unwise. (C) 2003 Elsevier Inc. All rights reserved.

Stem-completion priming for words studied in sentences: The context deletion effect under direct and indirect memory instructions

Two studies investigated the context deletion effect, the attenuation of priming in implicit memory tests of words when words have been studied in text rather than in isolation. In Experiment 1, stem completion for single words was primed to a greater extent by words studied alone than in sentence contexts, and a higher proportion of completions from studied words was produced under direct instructions (cued recall) than under indirect instructions (produce the first completion that comes to mind). The effect of a sentence context was eliminated when participants were instructed to attend to the target word during the imagery generation task used in the study phase. In Experiment 2, the effect of a sentence context at study was reduced when the target word was presented in distinctive format within the sentence, and the study task (grammatical judgment) was directed at a word other than the target. The results implicate conceptual and perceptual processes that distinguish a word from its context in priming in word stem completion.

Attending to the distractor and old/new discriminations in negative priming

When participants ignore an irrelevant distractor they typically show impaired responding to that item if it becomes the relevant stimulus on a subsequent trial. In Experiment 1 (N = 64), a masked white colour name was presented briefly before a Stroop display. Negative priming in colour naming occurred when the colour of the lettering for the Stroop stimulus matched the colour name displayed in the first display, consistent with the proposal of temporal discrimination theory that negative priming arises because a recurrence of an unattended stimulus cannot readily be classified as old or new. Experiment 2 (N = 32) replicated negative priming in the interleaved-word display where participants had to name the red word from a pair of red and green words. In Experiment 3 (N = 32) and Experiment 4 (N = 28) the participants were required to attend to but not respond to the words in the prime display and name one of two interleaved words in the probe display. Negative priming was observed in this arrangement, consistent with the episodic retrieval theory of negative priming. The temporal discrimination model may need to be extended to situations in which the attended stimuli have different responses attached to them.

The effects of different review opportunities on schematisation of knowledge

Recent research suggests that early in learning, students primarily use episodic memory when recalling information, but as learning develops and schematisation occurs, students' knowledge is likely to be dominated by semantic memory. This shift has been examined through student's memory awareness; 'remembering' is linked to episodic memory and 'knowing' is linked to semantic memory. This paper explores the effect of different review opportunities on students' memory awareness and schematisation, and reports on findings that indicate students are more likely to shift from 'remembering' to 'knowing' if they have the opportunity to review the learning material, but regularly and in different formats. (C) 2002 Elsevier Science Ltd. All rights reserved.

Is the effect of reading misspellings context dependent?

In 48 university students performing single-item spelling recognition, prior exposure to misspelled words improved slightly the accuracy on correctly spelled words and increased markedly the 'false alarm' rate (classifying a misspelling seen at study as correct). In a group given a dictation test (N = 24) the only effect of exposure to misspellings was a small increment in the number of misspellings that matched the misspelling seen at study. The two test groups showed no advantage of having the same display format at study and test (AA or BB vs AB or BA). Experiment 2 (in progress) investigated a format match at study and test against a condition with a new test context (AA or BB vs AC or BC). The results to date suggest an influence of memory of the study trial rather than simply an updating by the study exposures of abstract lexical representations. [ABSTRACT FROM AUTHOR]