The Regulation of miRNA-211 Expression and Its Role in Melanoma Cell Invasiveness

The immediate molecular mechanisms behind invasive melanoma are poorly understood. Recent studies implicate microRNAs (miRNAs) as important agents in melanoma and other cancers. To investigate the role of miRNAs in melanoma, we subjected human melanoma cell lines to miRNA expression profiling, and report a range of variations in several miRNAs. Specifically, compared with expression levels in melanocytes, levels of miR-211 were consistently reduced in all eight non-pigmented melanoma cell lines we examined; they were also reduced in 21 out of 30 distinct melanoma samples from patients, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic. The levels of several predicted target mRNAs of miR-211 were reduced in melanoma cell lines that ectopically expressed miR-211. In vivo target cleavage assays confirmed one such target mRNA encoded by KCNMA1. Mutating the miR-211 binding site seed sequences at the KCNMA1 3′-UTR abolished target cleavage. KCNMA1 mRNA and protein expression levels varied inversely with miR-211 levels. Two different melanoma cell lines ectopically expressing miR-211 exhibited significant growth inhibition and reduced invasiveness compared with the respective parental melanoma cell lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate suppressor of melanoma metastasis. The transcription factor MITF, important for melanocyte development and function, is needed for high TRPM1 expression. MITF is also needed for miR-211 expression, suggesting that the tumor-suppressor activities of MITF and/or TRPM1 may at least partially be due to miR-211's negative post transcriptional effects on the KCNMA1 transcript. Given previous reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and glioma, our findings that miR-211 is a direct posttranscriptional regulator of KCNMA1 expression as well as the dependence of this miRNA's expression on MITF activity, establishes miR-211 as an important regulatory agent in human melanoma

Impulsivity and Attention Deficit-Hyperactivity Disorder: Subtype Classification Using the UPPS Impulsive Behavior Scale

This study examined the classification accuracy of the UPPS Impulsive Behavior Scale (UPPS) in discriminating several attention deficit/hyperactivity disorder (ADHD) subtypes, including predominantly inattentive type (ADHD/I), combined type (ADHD/C), and combined type with behavioral problems (ADHD/ODD), between each other and a non-ADHD control group using logistic regression analyses. The sample consisted of 88 children ranging in age from 9.0 years to 12.8 years, with a mean of 10.9 years. Children were predominantly male (74%) and Caucasian (86%) and in grades 3–7. Results indicated that the UPPS performed well in classifying ADHD subtypes relative to traditional diagnostic measures. In addition, analyses indicated that differences in symptoms between subtypes can be explained by specific pathways to impulsivity. Implications for the assessment of ADHD and conceptual issues are discussed

Cerebral Tumors

EEG is an important diagnostic tool in cerebral tumors, useful to identify tumor-related ictal and interictal epileptiform abnormalities or slowings, to monitor antiepileptic treatment, and to address surgery. In this chapter we will discuss the general and specific characteristics of EEG in different cerebral tumors, with distinction among sites and types of lesion. Some considerations about the pathophysiological mechanisms underlying the EEG abnormalities and the EEG characteristics after surgery will be made at least