Using mouse models to explore genotype-phenotype relationship in Down syndrome

Down Syndrome (DS) caused by trisomy 21 is characterized by a variety of phenotypes and involves multiple organs. Sequencing of human chromosome 21 (HSA21) and subsequently of its orthologues on mouse chromosome 16 have created an unprecedented opportunity to explore the complex relationship between various DS phenotypes and the extra copy of approximately 300 genes on HSA21. Advances in genetics together with the ability to generate genetically well-defined mouse models have been instrumental in understanding the relationships between genotype and phenotype in DS. Indeed, elucidation of these relationships will play an important role in understanding the pathophysiological basis of this disorder and helping to develop therapeutic interventions. A successful example of using such a strategy is our recent studies exploring the relationship between failed nerve growth factor (NGF) transport and amyloid precursor protein (App) overexpression. We found that increased dosage of the gene for App is linked to failed NGF signaling and cholinergic neurodegeneration in a mouse model of DS. Herein, we discuss several mouse models of DS and explore the emergence of exciting new insights into genotype-phenotype relationships, particularly those related to nervous system abnormalities. An important conclusion is that uncovering these relationships is enhanced by working from carefully defined phenotypes to the genes responsible.     

Four dimensions of self-defining memories (specificity, meaning, content, and affect) and their relationships to self-restraint, distress, and repressive defensiveness

This study examines four dimensions of self-defining memory (specificity, meaning, content, and affect) and their relationship to self-restraint, distress, and defensiveness. The development and validation of a protocol for measuring specificity, meaning, and affect in self-defining memories is discussed. Specificity is operationalized as the temporal and detailed specificity of the narrative. Meaning refers to the participant's stepping back from the narrative to derive higher personal meaning or a life lesson. Affect reflects subjective emotion upon recall. Agreement between two raters scoring 1040 memories was kappa=.83 for specificity and kappa=.72 for meaning. The protocol is compatible with Thorne and McLean's scoring system for content (the types of events in memories). The current study compared individual differences in the four dimensions of 10 self-defining memories collected from 103 undergraduates to scores of self-restraint, distress, and repressive defensiveness, as measured by the Weinberger Adjustment Inventory. Memory specificity was inversely related to repressive defensiveness, while greater memory meaning was linked to moderate and high levels of self-restraint. Memory content and affect predicted individuals' degree of subjective distress. Based on these findings, the authors discuss the place of self-defining memories in Conway and Pleydell-Pearce's Self-Memory System model of autobiographical memory and personality, more generally.     

A Multiple‐Channel Model of Task‐Dependent Ambiguity Resolution in Sentence Comprehension

Traxler, Pickering, and Clifton (1998) found that ambiguous sentences are read faster than their unambiguous counterparts. This so‐called ambiguity advantage has presented a major challenge to classical theories of human sentence comprehension (parsing) because its most prominent explanation, in the form of the unrestricted race model (URM), assumes that parsing is non‐deterministic. Recently, Swets, Desmet, Clifton, and Ferreira (2008) have challenged the URM. They argue that readers strategically underspecify the representation of ambiguous sentences to save time, unless disambiguation is required by task demands. When disambiguation is required, however, readers assign sentences full structure—and Swets et al. provide experimental evidence to this end. On the basis of their findings, they argue against the URM and in favor of a model of task‐dependent sentence comprehension. We show through simulations that the Swets et al. data do not constitute evidence for task‐dependent parsing because they can be explained by the URM. However, we provide decisive evidence from a German self‐paced reading study consistent with Swets et al.'s general claim about task‐dependent parsing. Specifically, we show that under certain conditions, ambiguous sentences can be read more slowly than their unambiguous counterparts, suggesting that the parser may create several parses, when required. Finally, we present the first quantitative model of task‐driven disambiguation that subsumes the URM, and we show that it can explain both Swets et al.'s results and our findings.     

The Role of Christianity and Islam in Explaining Prejudice against Asylum Seekers: Evidence from Malaysia

ABSTRACT

Prejudicial attitudes toward asylum seekers are prevalent, and an emerging body of literature has revealed that this is partly driven by religious affiliation. The population of Malaysia is multireligious, making it a fruitful location for testing religion-based prejudice hypotheses. Thus, across 2 studies we tested the roles of Christianity and Islam in explicit and implicit prejudices against asylum seekers in the Malaysian context. In Study 1 (n = 97), we present evidence that there are religion-based differences in prejudice against asylum seekers; specifically, Muslims reported higher levels of (classical) explicit prejudice toward asylum seekers than Christians (there were no differences in conditional or implicit prejudices). In Study 2 (n = 117), we tested the hypothesis that these religion-based differences are qualified by the religion of the asylum seeker. In this study, we used a framing paradigm to experimentally manipulate the religion of the asylum-seeking targets. The results revealed an out-group exacerbation effect; that is, participants reported higher levels of prejudice toward asylum seekers who had a different religion from their own. For classical explicit prejudice, the effect was strongest from Muslims toward Christian asylum seekers. Conversely, for implicit prejudice, the reverse was true: The effect was strongest from Christians toward Muslim asylum seekers. These findings are discussed in terms of the political and social circumstances in Malaysia, but we interpret these findings as evidence that explicit and implicit attitudes toward asylum seekers are driven by a complex pattern of religion-based intergroup biases.