A Comparison of Aspiration Levels of Students in Ability-Grouped and Randomly-Grouped Schools

Grouping students with in the school setting has long been a concern to all those associated with the educative process. Much investigation has been devoted to the position of level of aspiration as influential motive forces for educational, occupational, and social achievement. Many avenues of grouping have been investigated and some very thoroughly. However, research concerning grouping in relation to level of aspiration in the school setting appears to be extremely limited. This study is designed to further investigate this issue. It might be said that this study consists of essentially two phases: (1) the development of instruments for measuring classroom aspiration, social aspiration, and educational aspiration; and (2) the determination of level of aspiration relationships which exist between junior high school boys grouped on the basis of ability and those randomly assigned to a classroom

Off-target response to decoy oligodeoxynucleotide treatment

*Background:* The transcription factor PAX2 regulates key developmental processes, including mediation of resistance to apoptosis. Inappropriate PAX2 expression has been implicated in facilitating tumour survival, and we have previously shown that siRNA-mediated blockade of PAX2 signalling at the transcript level in EJ bladder carcinoma cells promotes cell death. In this study, we attempted to disrupt PAX2 transcriptional activity in EJ cells by using a decoy oligodeoxynucleotide (ODN). 
*Results:* We could not show an interaction between PAX2 and our PAX2 decoy ODN, and in both 
PAX2-positive EJ and PAX2-negative HEK293 control cells, decoy and control ODN transfection resulted in a marked retardation of cell growth, irrespective of sequence, but not in COS7 and NZM4 melanoma cells. 
*Conclusions:* Our data indicate that decoy ODN transfection had off-target effects that inhibited cell growth in a cell line-dependent manner, and we suggest caution is required to determine the specificity of decoy ODN sequences before considering their application as a potential therapeutic agent

A Gene Expression Signature of Invasive Potential in Metastatic Melanoma Cells

BACKGROUND: We are investigating the molecular basis of melanoma by defining genomic characteristics that correlate with tumour phenotype in a novel panel of metastatic melanoma cell lines. The aim of this study is to identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management. PRINCIPAL FINDINGS: Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased expression of genes involved in interaction with the extracellular environment, such as PLAUR, VCAN, and HIF1a. Migration assays showed that the gene signature correlated with the invasive potential of the cell lines, and external validation by using publicly available data indicated that tumours with the invasive gene signature were less melanocytic and may be more aggressive. The invasion signature could be detected in both primary and metastatic tumours suggesting that gene expression conferring increased invasive potential in melanoma may occur independently of tumour stage. CONCLUSIONS: Our data supports the hypothesis that differential developmental gene expression may drive invasive potential in metastatic melanoma, and that melanoma heterogeneity may be explained by the differing capacity of melanoma cells to both withstand decreased expression of lineage specification genes and to respond to the tumour microenvironment. The invasion signature may provide new possibilities for predicting which primary tumours are more likely to metastasize, and which metastatic tumours might show a more aggressive clinical course

Retrotransposon hypomethylation in melanoma and expression of a placenta-specific gene.

In the human placenta, DNA hypomethylation permits the expression of retrotransposon-derived genes that are normally silenced by methylation in somatic tissues. We previously identified hypomethylation of a retrotransposon-derived transcript of the voltage-gated potassium channel gene KCNH5 that is expressed only in human placenta. However, an RNA sequence from this placental-specific transcript has been reported in melanoma. This study examined the promoter methylation and expression of the retrotransposon-derived KCNH5 transcript in 25 melanoma cell lines to determine whether the acquisition of 'placental' epigenetic marks is a feature of melanoma. Methylation and gene expression analysis revealed hypomethylation of this retrotransposon in melanoma cell lines, particularly in those samples that express the placental KCNH5 transcript. Therefore we propose that hypomethylation of the placental-specific KCNH5 promoter is frequently associated with KCNH5 expression in melanoma cells. Our findings show that melanoma can develop hypomethylation of a retrotransposon-derived gene; a characteristic notably shared with the normal placenta

MITF and PAX3 play distinct roles in melanoma cell migration; outline of a genetic switch theory involving MITF and PAX3 in proliferative and invasive phenotypes of melanoma

Melanoma is a very aggressive neoplasm with a propensity to undergo progression and invasion early in its evolution. The molecular pathways underpinning invasion in melanoma are now just beginning to be elucidated, but a clear understanding of the transition from non-invasive to invasive melanoma cells remains elusive. Microphthalmia-associated transcription factor, MITF, is thought to be a central player in melanoma biology, and it controls many aspects of the phenotypic expression of the melanocytic lineage. However, recently the paired box transcription factor PAX3 was shown to transcriptionally activate POU3F2/BRN2, leading to direct repression of MITF expression. Here we present a theory to explain melanoma phenotype switching and discuss the predictions that this theory makes. One prediction is that independent and opposing roles for MITF and PAX3 in melanoma would be expected, and we present empirical evidence supporting this: In melanoma tissues PAX3 expression occurs independently of MITF, and PAX3 does not play a key role in melanoma cell proliferation. Furthermore, we show that knockdown of PAX3 inhibits cell migration in a group of lower MITF melanoma cell lines, while knockdown of MITF promotes cell migration in a complementary higher MITF group of melanoma cell lines. Moreover, the morphological effects of knocking down PAX3 versus MITF in melanoma cells were found to differ. While these data support the notion of independent roles for MITF and PAX3, additional experiments are required to provide robust examination of the proposed genetic switch theory. Only upon clear delineation of the mechanisms associated with progression and invasion of melanoma cells will successful treatments for invasive melanoma be developed

Gene Set Enrichment Analysis with microarray expression data from the renal cortex and medulla of rats fed lithium for 6 months.

<p>The mean signal intensity of a probe set (a surrogate value of expression level) across all lithium-fed samples (y-axis) is plotted against the mean signal intensity across all control samples (x-axis). Each point represents a single probe. <b>(A)</b> Gene sets with functional gene annotation enrichment for MARGS, fibrosis, TGFβ2 and ECM genes in the renal cortex; <b>(B)</b> Gene sets with functional gene annotation enrichment for MARGS, immune response, TGFβ2 and ECM genes in the medulla. With the exception of the MARGS gene set, all gene sets in this figure were extracted from <a href="http://www.SABiosciences.com" target="_blank">www.SABiosciences.com</a>.</p

Principal component analysis (PCA) and hierarchical cluster analyses of MARGS in the renal cortex (A) and medulla (B) of kidneys from control and lithium-fed rats (6 months).

<p><b>A.</b> PCA (left) and hierarchical cluster analysis (right) using 5 MARGS genes from cortex (expression filtered, p-value < 0.05, |FC| > 1.5); <b>B.</b> PCA (left) and hierarchical cluster analysis (right) using 11 MARGS genes from medulla (expression filtered, p-value < 0.05, |FC| > 1.5). MARGS are sufficient to separate the two groups. In PCA, each sphere represents one sample. The ellipsoids represent 95% of the data of a group. In both PCA plots in A and B, red indicates expression above median, blue indicates expression below median. The depth of the colour indicates extent of expression above or below median.</p