Publication Type: Poster
Review Method: Peer Reviewed
Abstract: 3rd place 2008 Disseration Award -Melanie completed her dissertation at Fordham University under the supervision of Barry Rosenfeld.
Atkins has stimulated concern about ruling out malingering in offenders claiming mental retardation. In this study comparing honest individuals with genuine mental retardation to simulators, the DCT misclassified many honest respondents, while the SIRS tended to misclassify those with comorbid psychopathology. The TOMM misclassified the fewest honest respondents, and a model combining it with the SIRS correctly classified almost all participants. Measures were not correlated with each other or with estimated IQ. Cutoff scores were suggested to optimize specificity when using these measures in Atkins contexts. These cutoffs substantially decreased sensitivity for the DCT and SIRS but not the TOMM.

Publication Type: Poster
Abstract: Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein FMRP. Given that the disease may arise from the absence of FMRP during early neuronal development, studies using hESC-derived neuronal cells would provide novel insights into the underlying molecular mechanism of FXS at the very earliest stages of brain development. As an RNA-binding protein, FMRP executes its function through interaction with bound mRNAs. Identification of FMRP RNA targets in the early stage neuronal cells is thus an essential step towards understanding FMRP’s function.

As a first step toward this goal, we will focus on creating FMR1 knockout (KO) hESC lines that will serve as crucial control lines in our next step experiments (see below). Thus, we will clone short hairpin RNAs (shRNAs) into plasmid-based or lentiviral-based vectors to create siRNA-expressing vectors that allow specific FMR1 gene silencing upon stable transfection into hESC. We will then screen a spectrum of shRNAs to identify those that have the ability to optimally inhibit FMR1 gene expression in hESC lines. We will use quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analysis to moniter the efficacy of gene silencing. Once stably FMR1 KO lines are obtained, we will perform karyotyping analysis to ensure that they show no evidence of chromosomal abnormalities. Since FXS patients can produce viable embryos, we expect that FMR1 KO lines will have a normal gross phenotype.

Next, we will identify FMRP mRNA targets as well as associated microRNAs in hESC-derived neuronal cells, using immunoprecipitation (IP) and microarray screening. We will then validate the targets functionally by comparing the expression profiles of selected targets between wild type (WT) and KO hESC-derived neuronal cells. To identify mRNAs associated with FMRP in hESC-derived neuronal precursor cells (maintained as neurospheres), we will specifically isolate FMRP-containing protein-mRNA complexes by IP using an FMRP-specific monoclonal antibody and identify the copurified mRNAs by microarrays. We will prepare fresh cell lysates from neurospheres derived from WT or KO hESC lines. The KO is used as a negative control for both IP and microarray analyses. Once we have obtained putative FMRP mRNA targets, we will commence the process of rigorous data validation. We will first confirm the in vivo binding using qRT-PCR following IPs. We will then test whether the binding is direct by in vitro assays. We will consider those that score high in all assays the most likely in vivo targets. To identify possible FMRP-associated microRNAs we will perform IP and Northern blot analyses. Both FMRP and microRNAs have been implicated in the regulation of translation. Identification of specific microRNAs associated with FMRP in the human neuronal cells would further support the hypothesis that FMRP-mediated translational control may be mechanistically linked to the microRNA pathway.

Finally, we will perform functional validation of FMRP mRNA targets. FMRP has been shown to act as a translational modulator of its bound mRNAs in vitro. To test whether FMRP does so in human neuronal cells, we will examine the impact of FMR1 KO on the abundance of proteins encoded by the target mRNAs. Western blot analysis on protein samples extracted from neurospheres derived from WT and KO hESC lines will be carried out. We will use antibodies specific for proteins encoded by a selected subset of target mRNAs identified as described above. We will also examine the levels of proteins whose mRNAs are likely not targets of FMRP and therefore ones where we do not expect to see changes between WT and the KO samples. Results derived from our studies will shed new lights onto the molecular function of FMRP, hence aiding in the eventual development of successful interventions for FXS.

Publication Type: Poster
Abstract: In 2002, the Supreme Court held in Atkins v. Virginia that individuals with mental retardation (MR) could not be executed. Two judges’ evaluations of expert testimony in the Green v. Johnson (2006, 2007) post-conviction federal habeas corpus hearing illustrate the challenge of making post-conviction MR determinations. The judges accepted expert testimony that it was necessary to consider improvements in mean IQ test performance (the Flynn effect) when interpreting Green’s IQ scores and found that he met the IQ criterion for MR. However, the judges ruled that Green did not have MR because he lacked significant deficits in adaptive functioning

Publication Type: Paper (prepared oral presentation)
Abstract: Immigration in Greece is a fairly new experience since it started in the ‘90s. This presentation aims to look at the role that the concept of culture plays in the representation that Greeks have of a society in which they co-exist with immigrants and in their negative attitudes towards them. Starting with the hypothesis that national majorities resist the social mobility of immigrants because it diminishes the distance between their ingroup and themselves (see Social Identity Theory Tajfel and Turner 1979, 1986), it will be argued that Greeks are against immigration because it changes the social stratification and endangers their own position. Findings from three experimental studies will be presented. In the first two studies the social mobility (horizontal and vertical) of immigrants and their origins were manipulated in order to study these effects on the attributions of success or failure of immigrants from different countries to be socially mobile. In these studies culture is used by participants to explain the barriers to social mobility only of immigrants from particular countries. In the third study we manipulated the attribution of violent immigrant riots either to cultural or social reasons and studied the effect of these attributions on Greeks’ attitudes towards multiculturalism. Again culture organizes people’s beliefs and the types of intergroup conflicts expected. The results from all three studies show that Greeks use “culture” as a way to explain social differences in order to oppose social mobility for immigrants and the formation of solidarity at a class level.

Publication Type: Symposium Paper
Abstract: Concerns about malingered mental retardation in criminal settings have grown in the post- Atkins era. Despite the substantial proportion of inmates with below-average intellectual functioning, little research investigates the accuracy of malingering detection measures when respondents have genuine intellectual disabilities. Evidence is presented that the DCT poorly differentiated community-dwelling individuals with mild mental retardation from simulated malingerers, misclassifying a large proportion of honest respondents, while classifications based on the SIRS and TOMM were more accurate in this sample. Suggestions are made as to cutting scores that optimize specificity when these measures are used with respondents who have intellectual disabilities.